This document contains our coverage of epidemiology, education, and additional topics at ADA 2017. Immediately below, we enclose our themes on the category, followed by detailed discussion and commentary. Talk titles highlighted in yellow were among our favorites from ADA 2017; those highlighted in blue are new full report additions from our daily coverage.
For comprehensiveness, we have included some talks in this report that also overlap with our ADA 2017 Diabetes Complications, Policy and Reimbursement, and Treatment Algorithms and Strategies reports.
Psychosocial Care in Diabetes
- This year marked the first time the Scientific Sessions have focused explicitly on psychosocial aspects to diabetes care. At a Friday press conference, Dr. Korey Hood (Stanford University, CA) reviewed the new ADA/APA (American Psychological Association) position statement on this topic, which also led the ADA to incorporate psychosocial support into its 2017 Standards of Care and to feature more research of this genre at ADA 2017. Most notably, the ADA Presidents Oral Session on Tuesday morning included Dr. Mary de Groot’s presentation of Program ACTIVE II study results. This trial randomized people with type 2 diabetes and clinical depression (n=150) to one of four arms for 12 weeks: (i) exercise with a personal trainer, (ii) talk/cognitive behavioral therapy, (iii) exercise plus talk/cognitive behavioral therapy, or (iv) usual care. All three interventions were associated with statistically significant improvements in depressive symptoms (p<0.05), diabetes distress (p<0.01), and quality of life (p<0.05) vs. usual care. Participants in any of the intervention groups also reported fewer negative automatic thoughts after 12 weeks (p<0.03 vs. usual care). These beneficial effects were sustained when controlling for antidepressant medication use, underscoring the efficacy of both exercise and therapy as approaches to psychosocial care. Drs. Hood and de Groot were both authors on the ADA/APA position statement, which they described as a major collaborative effort. The overarching goal outlined is to enhance training of mental healthcare professionals so they’re better-equipped to screen for and treat diabetes distress and comorbid diabetes/depression. That said, in order to broaden and maximize the impact of improved psychosocial care for a diabetes patient population, endocrinologists and primary care physicians who treat diabetes will also have to be trained to increase screening and referrals. “There’s a lot left to do,” Dr. Hood emphasized. The new position statement and higher number of related abstracts at this conference are small steps in the right direction. Next, the ADA/APA have to devise ways to make sure psychosocial care is implemented in a cost-effective and evidence-based manner, Dr. Hood explained – to this end, studies like Program ACTIVE II that identify specific, effective approaches to psychosocial support are so valuable. A follow-up meeting between the two professional organizations is scheduled for August 2017. We’re eager to see what comes of this partnership and position statement, and to observe positive effects in real-world clinical settings, though this will likely take some time. We’re glad to note ADA’s commitment to spreading awareness/education of the position statement on psychosocial care. The ADA’s Standards of Care, for example, are influential around the globe, and we so hope diabetes providers and mental healthcare providers alike take notice and change their practice to give patients the best possible comprehensive care.
- As always, the award lectures sparked inspiration amongst all who attended. Ms. Davida Kruger (Henry Ford Medical Group, Detroit, MI) delivered an absolutely moving Outstanding Educator in Diabetes Award Lecture, detailing her impressive dedication to the field over the past 35 years. Columbia’s Dr. Domenico Accili discussed exciting developments in diabetes research, anticipating massive changes in the way diabetes will soon be managed. And, Ms. Brenda Montgomery, ADA President of Healthcare and Education, discussed the ADA’s noteworthy efforts in the fight to prevent diabetes.
- Diabetes educator extraordinaire Ms. Davida Kruger delivered the Outstanding Educator in Diabetes Award Lecture, providing insights on her role in the DCCT, as a nurse practitioner in diabetes, and as an ADA volunteer. Ms. Kruger stressed the increasingly important role of the nurse practitioner, presenting data showing that nurse practitioners make equally accurate diagnoses as physicians and are also more likely than physicians to provide health education and promotion, adapt medical regimens to the patient’s preferences, and listen more to the patient. Ms. Kruger closed by stating that the field “must remain open to all team members” and keep the patient at the “head of the team.” Ms. Kruger deservedly left the podium with a standing ovation, and our team joins the diabetes world in our deepest gratitude and admiration for Ms. Kruger’s incredible leadership and service to the field.
- In this year’s inspiring Banting Medal for Scientific Achievement lecture, Columbia’s Dr. Domenico Accili presented his vision of a revamped toolkit for diabetes care in 2021, 100 years after the discovery of insulin: Prevention of beta cell de-differentiation, a gut-targeted Foxo1 inhibitor to coax gut cells into producing insulin in a glucose-dependent manner, and selective insulin sensitizers. The meat of his talk focused on dispelling the perception that beta cell failure is a consequence of beta cell death; rather, his data suggest that beta cell dedifferentiation is to blame. Dr. Accili sees a big opportunity here: If beta cells are not dead, but just quiescent as dedifferentiated of converted cells, then there’s a chance to restore beta cell health even after the onset of hyperglycemia. For type 1 diabetes, Dr. Accili’s lab has set sights on coaxing gut cells into producing insulin in a glucose-dependent fashion, and for type 2 diabetes, Dr. Accili explained that it is possible to modulate critical nodes of insulin signaling to dial up/down individual bio-responses, enabling selective reversal of insulin resistance. With a portfolio this lengthy and deep, we can’t think of anyone more deserving of this award than Dr. Accili – our only hope is that he sticks with it and delivers 2021: A Diabetes Odyssey.
- Ms. Brenda Montgomery, ADA President of Health Care & Education, gave a speech on ADA’s efforts in the fight to prevent diabetes. Last year’s President’s address by Dr. Desmond Schatz, in which he pleaded with attendees to bring diabetes to “the boiling point of water where it erupts with urgency” was a tough act to follow, but Ms. Montgomery delivered. In particular, Ms. Montgomery focused on prevention, organizing her remarks in accordance with the ADA’s three strategic imperatives: (i) Drive Discovery, through research, partnership, and innovation; (ii) Raise Voice, to intensify the urgency around the diabetes epidemic and mobilize action; and (iii) Support People, to continually develop new and effective resources for people affected by diabetes. Ms. Montgomery characterized the ADA’s work in the prevention space as a story of “small steps leading to big rewards.” Though we have yet to see fruits from those labors, we certainly applaud and thank all involved for their time and effort.
Detailed Discussion and Commentary
Oral Presentations: ADA Presidents Oral Session
Program ACTIVE II: A Comparative Effectiveness Trial to Treat Major Depression in T2DM
Mary de Groot, PhD (Indiana University School of Medicine, Indianapolis, IN)
Dr. Mary De Groot presented the Program ACTIVE II study, a 12-week evaluation of exercise, talk/cognitive behavioral therapy, and exercise plus therapy as psychosocial interventions for people with type 2 diabetes and comorbid clinical depression (n=150). All three interventions were associated with statistically significant improvements in depressive symptoms (p<0.05), diabetes distress (p<0.01), and quality of life (p<0.05) vs. usual care. Patients randomized to any of the three treatment arms reported fewer negative automatic thoughts (p<0.03 vs. usual care). These effects were sustained even after controlling for antidepressant medication use, which underscores the distinct benefit to exercise support (12 weeks with a personal trainer) and to talk/cognitive behavioral therapy (10 sessions over the course of 12 weeks). Importantly, Program ACTIVE II enrolled adults from diverse income levels and educational backgrounds, each of which independently affects psychosocial health. We were extremely pleased to hear this data as part of the ADA Presidents Oral Session, a decision that speaks to the organization’s growing emphasis on the psychosocial aspects to diabetes care. In fact, we learned that this is the first annual scientific sessions with an explicit focus on psychosocial treatment, and it comes on the heels of the ADA/APA (American Psychological Association) position statement on psychosocial care for people with diabetes. Notably, the ADA’s 2017 Standards of Care also reflects this emphasis on psychosocial support.
Oral Presentations: Prediction and Prevention of Cardiovascular Complications
Genetic Predictors of Cardiovascular Outcomes during Intensive Blood Pressure Control in ACCORD
Hetal Shah, MD (Joslin Diabetes Center, Boston, MA)
The 2008 ACCORD trial demonstrated that intensive blood pressure control did not improve cardiovascular outcomes in people with type 2 diabetes overall, but using a genome-wide association screen, Dr. Hetal Shah and her team identified genetic variants that could be used to pinpoint the subset of people with diabetes for whom intensive blood pressure is effective for the prevention of cardiovascular outcomes. The researchers conducted a GWAS test for 6.8 million common genetic variants for association with the primary outcome of 3-point MACE (cardiovascular death, non-fatal MI, and stroke) among consenting study participants (n=1,151) in the intensive blood pressure control arm of the ACCORD study. One loci on 2p22 exceeded the threshold (p=5x10-8) for genome-wide significance: an intron on 2p22 near the non-coding RNA gene LOC101929596 (p=3x10-8). Four other loci achieved near-threshold significance (p<10-7) – SNPs in close proximity to the non-coding RNAs on 22q21 and 18q2, the HDAC9 gene on 7p21, and the Syntaxin-8 gene on 17p13 responsible for protein trafficking. Sixteen other loci achieved notable significance (p<10-6). In a joint analysis of both the intensive and standard blood pressure control arms of the ACCORD study (n=2,295), individuals with the dominant allele for the top SNP experienced a significant benefit in the primary outcome when undergoing intensive blood pressure control (HR 0.66; 95% CI 0.49-0.88; p=0.006), whereas those with the recessive allele actually experienced a near doubling in cardiovascular events in response to intensive therapy (HR 2.22; 95% CI: 1.21-4.06; p=0.01). Dr. Shah was careful to note that these findings must be confirmed in additional studies, but this preliminary evidence provides an important basis for a future precision medicine approach to preventing cardiovascular events in people with type 2 diabetes. While we look forward to a future where an individual’s genetic makeup can be used to inform what strategy for blood pressure management has the best chance of preventing cardiovascular events, there is a long road ahead on this front – nonetheless, we’re glad to see the continued immense interest and progress in this area!
Oral Presentations: Venturing Beyond the Bricks, Mortar, and Books
Global Patterns of Treatment Changes among Patients with Type 2 Diabetes (T2DM) Treated with Insulin: Insights from the MOSAIc Observational Study
Melanie Davies, MD (University of Leicester, UK)
Dr. Melanie Davies presented the results of MOSA1c, an 18-country observational study following insulin-treated patients with type 2 diabetes (n=4,299) in order to determine what types of treatment changes occur across two years of follow up. 89% of participants in the study had a personalized A1c target, though 95% of them had an A1c above this target during the time of the study. 38% of patients in the study experienced a treatment change (defined as addition of an insulin injection, change in/additional insulin type, addition of GLP-1 receptor antagonist, addition of an oral antidiabetes drug, or insulin dose escalation) within 6 months of an elevated A1c, while 34% had no treatment change during follow-up. Patients with A1c values more than 1.5% above target were more likely to undergo a treatment change. However, more than half of insulin-treated patients with type 2 diabetes and elevated A1c did not receive recommended treatment change within 6 months after exceeding their personalized target. For patients with multiple instances of treatment change, the most common forms of treatment change were insulin dose escalation (60%), addition of an insulin injection (43%), and change in or addition of insulin type (41%). Patients with treatment change were slightly younger, white, married or cohabiting, and were more likely to have macrovascular complications, heart failure, and public health insurance. Physicians who initiated treatment changes tended to have slightly less time spent with patients to manage diabetes care and slightly larger number of diabetes patients treated in the last month. These fascinating results provide a comprehensive view of global trends in diabetes treatment, and we hope a deeper dive into the MOSA1c findings can foster a deeper understanding of the challenges associated with the intensification of diabetes therapy.
Oral Presentations: Potential Implications of the Affordable Care Act on Diabetes Care
Trends in the Costs of Diabetes-Related Preventable Hospitalizations, 2002-2013
Sundar Shrestha, PhD (CDC, Atlanta, GA)
Dr. Sundar Shrestha presented data showing an increased cost burden of total diabetes-related preventable hospitalizations (DRPH) between 2002-2013. The study used data from this time period from the US National Inpatient Survey, analyzing mean length of stay and cost per inpatient day. Dr. Shrestha shared that cost per admission remained stable for short-term complications and lower extremity amputations, but increased slightly for long-term complications and uncontrolled diabetes. Notably, mean length of stay declined (by 0.3% to 2.2% annually) for all types of DRPH but cost per inpatient day increased (by 2.1% to 3.4% annually). Dr. Shrestha concluded that the total DRPH cost burden increased due to increasing trends in the number of discharges, likely due to increasing diabetes prevalence, as well as increasing trends in mean DRPH costs (due to increased cost per inpatient day). In closing, Dr. Shrestha stressed that these findings reinforce the need for continued efforts toward alleviating diabetes burden and improving ambulatory care and diabetes management, and he called for further research into these cost trends. In all, we agree that these data continue to emphasize the importance of prevention and earlier diabetes intervention, as the burden of complications and their financial implications remains significant.
Questions and Answers
Q: You noted that as the length of admission is falling, but the cost per day of admission is rising. Is that specific to diabetes or is it a general trend?
A: We think this is an area for research. There have been no complete studies to look at this. We don’t know exactly the reason.
Q: I was struck by the short-term complications and how there was really no change in that timeframe. And this seems to be an ongoing burden that we’ve not yet conquered. Do you have additional insights regarding short-term complications?
A: We’re actually not sure – we need to look at more detailed data.
Oral Presentations: Hospital-Based Care and Diabetes – Adherence to Diabetic Care Strategies
Association Between Oral Diabetes Agent Adherence, Age, Comorbidities, and A1c among Elderly Patients
Gregory Nichols, PhD (Kaiser Permanente, Portland, OR)
Dr. Gregory Nichols presented results from an analysis examining the effect of age, comorbidities, and A1c on adherence to oral diabetes medications among elderly patients (age ≥65). The analysis involved 2010 electronic health record (EHR) data for ~54,000 patients in three Kaiser Permanente health systems. Of these patients, 48,803 were considered to be in good control (A1c <8%), while 1,708 were considered to be in poor control (A1c >9%). The analysis found that the oldest patients (age ≥85) were 2% less likely to be adherent vs. younger patients. Moreover, patients with at least four comorbidities were 10% less likely to be adherent vs. those with fewer comorbidities. We wonder whether these results might be different in a population with more typical adherence rates: As noted during Q&A, adherence was quite high in both groups, at 83% in the cohort with good control and at 71% in the cohort with poor control (patients were considered adherent if they had ≥80% of days covered based on prescription fills). We also wonder how a different definition of adherence might affect these findings (for example, patients might fill more than 80% of their prescriptions but not actually take all the medication). Dr. Nichols’ main conclusion from the results (based on the rationale for the study), was that CMS should take factors such as age and comorbidity status into account when creating financial incentives for Medicare Advantage plans based on metrics including adherence.
Questions and Answers
Q: Was there an explanation for the relatively high adherence in this study? A lot of studies suggest adherence rates on the order of 60%. Maybe older people have greater adherence?
A: Better adherence is common among those over 65. Kaiser does a good job at this. The adherence rates here weren’t out of line with other studies I’ve done.
Q: You mentioned that adherence was dichotomized, but did you also look at it as a continuous variable?
A: We didn’t. Based on other studies, dichotimization makes sense for reasons beyond just convenience. People really are or aren’t adherent. There’s a large cluster at zero and a large cluster at 80-90%, and the rest are dispersed throughout.
Oral Presentations: The Epidemiology of Diabetes Complications
Glycemic Control, Glucose-Lowering Medication Use, and Utilization among Older Patients with Diabetes
Jennifer Kuntz, PhD (Kaiser Permanente Center for Health Research, Portland, OR)
Dr. Jennifer Kuntz presented the results of an analysis investigating the impact of number of medication classes and A1c on healthcare utilization among older patients with diabetes (age ≥65). The goal was to gain insights that can help providers individualize therapy for older patients, where it can be particularly difficult to strike the right balance between tight control and avoiding negative effects of medications. The analysis involved 10,091 patients with diabetes in the Kaiser Permanente Northwest Diabetes Registry. Of those patients, 5,065 were considered to have tight control (A1c <7%), 4,386 had moderate control (A1c 7-8.9%), and 640 had poor control (A1c ≥9%). Results showed that 84% of patients in the tight control group were taking medications from at least two different diabetes drug classes, compared with 70% of the poor control group. The analysis also found, however, that patients achieving tight control with two or more medication classes had 24% more hospitalizations and 37% more hospital days compared to those achieving tight control with fewer than two classes. The same group (tight control and at least two medication classes) had 55% more hospitalizations and 63% more hospital days than patients with moderate glycemic control taking fewer than two medications. There was no significant difference between groups in outpatient and emergency room visits. Dr. Kuntz concluded that this study suggests that overtreatment may be hazardous for elderly patients, generating unnecessary healthcare utilization in the form of emergency care or hospital visits. As was discussed during Q&A, it would be interesting to see more granular results looking at the effect of specific medications on healthcare utilization. For example, we would not be surprised if insulin use was the main factor behind the increased hospitalizations in the group taking more medication classes. Moreover, we don’t like the idea of any patient – old or young – having to sacrifice their desired glycemic target due to the risks associated with tight control, and instead would love to see CGM use and better patient education to manage these risks and avoid hyperglycemia. For patients who must take mealtime insulin, of course, those are real risks as they are for patients on SFUs (like Dr. Ralph de Fronzo, we wish no patients had to take these.)
Questions and Answers
Q: What were the excess hospitalizations for? Did you look at insulin as a different class? A patient just on insulin may be taking three boluses a day, which is quite complex, but that person would be lumped into the same group as someone just taking metformin.
A: We haven’t looked at the reasons for hospitalization yet. We looked at hypoglycemia and didn’t see many events, but we were not that rigorous in trying to find them. The next step is to dig into more of the complexities in different medications.
Q: More than 80% of the population with an A1c <7% was on fewer than two medications. Did you look at what proportion was not on any medications? If so, are you worried that some of them were false positives for having diabetes?
A: We did look at those taking zero medications. We relied on the fact that our diabetes registry data is very rich. I don’t think there were any false positives.
Global Prevalence of Type 2 Diabetes Complications in 14,391 Patients Initiating Second-Line Therapy: The DISCOVER Study
Mikhail Kosiborod, MD (University of Missouri, Kansas City, MO)
The DISCOVER study was an effort to more accurately quantify the prevalence of micro and macrovascular diabetes complications around the world. As Dr. Mikhail Kosiborod established at the start of his talk, these prevalence values are not currently well-described. The DISCOVER research group collected patient data from both primary care and diabetes-specific healthcare settings. The overall adjusted prevalence of macrovascular complications was 13%, but ranged from 4.1% to 46.6% across countries. The overall adjusted prevalence of microvascular complications was 17.7%, ranging from 5.5% to 41.1% across countries. Macrovascular complications included coronary artery disease, heart failure, stroke, and peripheral artery disease, while microvascular complications included retinopathy, nephropathy, and neuropathy. Dr. Kosiborod concluded that there is a substantial global burden of micro and macrovascular complications of diabetes, one that should be addressed through more rigorous screening for risk factors.
- Strengths of study include a large number of patients from regions across the world (37 countries across 6 continents). The list includes countries like Panama, Costa Rica, and Bahrain, which have rarely been studied before, at least not in the context of diabetes epidemiology. Another strength of the study design, according to Dr. Kosiborod, was use of a standardized electronic case report form to facilitate comparisons across multiple countries and regions.
- Study limitations include the possibility of suboptimal screening for complications in developing or rural regions, as well as the potential for biased reporting of complications, since this was somewhat subject to an investigator’s judgment.
Oral Presentations: Race and Societal Influences on Diabetes
The Productivity Burden of Diabetes
Dianna Magliano, PhD (Monash University, Melbourne, Australia)
Dr. Dianna Magliano estimated diabetes to yield a 27% reduction and 19% reduction in Productivity Adjusted Life Years (PALYs) for Australian males and females, respectively. In an effort to expand what is a remarkably lacking area of research, Dr. Magliano took matters into her own hands and designed PALYs by applying a known productivity index across two 2011 life tables from the National Diabetes Service Scheme (NDSS), one table of people with diabetes and one without. To determine the productivity loss attributed to diabetes, she subtracted PALYs from those without diabetes from those with diabetes. PALYs lost due to diabetes were most apparent in those aged 20-65, the working age population. This work further highlights the importance of preventing diabetes and caring for those with diabetes. Dr. Magliano hopes that future work will focus on linking PALYs with a monetary value, providing financial insight to leverage improved care for people with diabetes at the population level.
The Burden of Diabetes, Hypertension, and Noncommunicable Disease Risk Factors among Adults Aged 30 Years and Above in Rural Bangladesh– A Cross-Sectional Epidemiological Survey
Kishwar Azad, MSc (BIRDEM and Ibrahim Medical College, Dhaka, Bangladesh)
Ms. Kishwar Azad won the Vivian Fonseca Scholar Award this year for her work surveying risk for type 2 diabetes, impaired fasting glucose, impaired glucose tolerance, hypertension, and common noncommunicable diseases in rural Bangladesh. Ms. Azad’s team reached out to 96 villages in the area and surveyed 12,280 individuals older than 30. Results showed a high risk of type 2 diabetes in this population, based on a high frequency of impaired glucose tolerance (15.6%). Diabetes prevalence in this population increased with age, and the chronic disease was also more common in women. A striking finding from this analysis was that a third of the participants had never heard of diabetes. Among those who had heard of it, 70% did not know the causes, and 75% of those found to have type 2 diabetes were unaware of their condition. Ms. Azad’s presentation was an important reminder that the type 2 diabetes crisis is truly global, and her inspiring work offers some hope that we can spread diabetes education and screening to combat this worldwide epidemic (though so much work remains to be done).
Questions and Answers
Q: What kind of training did the individuals who collected the data have?
A: They each received one week of training.
Q: More and more around the world, we’re seeing a higher prevalence of diabetes in men vs. women, but you found the opposite. Why would that be?
A: It’s hard to say, and there could be many reasons. One possibility is that women in rural Bangladesh do not exercise often, since their work is such that they are mostly in the house. I don’t like to say that they’re unemployed, but they work all day in the house and it’s very sedentary. They don’t go outside and get that same level of physical activity as men.
Q: How did you do the psychological assessment in this study?
A: We used a guided survey, I can’t remember exactly which right now.
Q: Did you also collect information from youth under 30, considering the higher rate of type 1 diabetes in that population?
A: This survey was mainly for type 2 diabetes. We have another program looking at type 1, and we have one that is sponsored by Novo Nordisk.
Oral Presentations: Novel Approaches to Improving Adherence in T2D
Stepped-Care Behavioral Intervention Reduces Regimen-Related Distress
Doyle Cummings, PharmD (East Carolina University, Greenville, NC)
People with type 2 diabetes have higher prevalence rates of depressive and distress symptoms than the general population, and these comorbidities are associated with poorer glycemic control and self-care. However, the impact of lowering these symptoms in rural primary care patients is inadequately described. Dr. Cummings presented his work on the COMRADE trial, which looked at the feasibility of delivering an integrated behavioral health intervention in a rural primary care setting for patients with type 2 diabetes with A1c above goal (>7%) and comorbid distress. The study population had an average A1c above 9, were middle age, and were predominantly female and African American. The trial was designed as a randomized prospective pragmatic comparative effectiveness pilot study and was held at an academic family medicine center serving a large rural area. Treatment was integrated behavior intervention (cognitive behavioral therapy and lifestyle modification) compared to usual care, with the intervention delivered twice a month for six months, plus telephone support. First, researchers stratified the population by depression (as assessed by the PHQ-9 questionnaire) and diabetes distress (as assessed by the DDS-17 questionnaire), with patients with higher scores receiving cognitive behavioral therapy from a psychologist, and those with lower scores receiving coaching on behavioral small changes lifestyle by a nurse. After the intervention, participants experienced significant reductions in DDS-17 diabetes distress measures like regimen-related distress, emotional burden, and interpersonal burden. However there was no statistically significant improvement in A1c. Interestingly, improvement in regimen-related distress was the most significantly correlated with improvement in A1c. Overall, the COMRADE study demonstrates that it is feasible to implement screening and interventions for behavioral issues in a rural setting, and behavioral health interventions can lower distress and depressive symptoms more than usual care.
Oral Presentations: Physiological Effects of Exercise in Humans with Diabetes or Obesity (With State-of-the-Art Lecture)
State-of-the-Art Lecture: Emerging Mechanisms Underlying the Benefits of Exercise for Diabetes
Bret Goodpaster, PhD (Translational Research Institute, Orlando, FL)
In his state-of-the-art lecture, Dr. Bret Goodpaster emphasized the importance of exercise for individuals with type 2 diabetes, asserting that no matter the patient’s age, exercise ultimately helps with glucose control. When individuals exercise, they are affecting their skeletal muscles. People with diabetes who exercise frequently will have high mitochondrial content in the intermuscular tissue, and with each contraction of the muscle, they increase their glucose uptake from the blood– a direct mechanism to counteract hyperglycemia. As a part of the normal aging process, the amount of intermuscular adipose tissue increases, which also raises the likelihood of storing fat and lowers the rate of glucose uptake. Physical activity will decelerate the growth of intermuscular adipose tissue, and exercise is thus beneficial in both the short and long term for people with type 2 diabetes. Additionally, studies have shown that exercise following bariatric surgery improves insulin sensitivity and mitochondrial activity.
Oral Presentations: Mechanisms and Modulators of Cardiovascular Complications (With Edwin Bierman Award Lecture)
Edwin Bierman Award Lecture – Metabolic Karma – The Atherogenic Legacy of Diabetes
Mark Cooper, PhD (Monash University, Melbourne, Australia)
In this presentation, Dr. Mark Cooper explained how the history of an individual’s metabolic control can influence that individual’s future health. According to the legacy effect, positive metabolic control efforts lead to persistent long-term benefits, while inadequate control may have negative consequences in the long term. This is important because when post-mitotic cells are lost during poor glucose control, there is no way for those cells to regain their functions. As a result, vascular complications result from a history of poor glycemic control due to accumulated cellular modifications, including increased reactive oxygen species (ROS) production and decreased antioxidant protection. Hyperglycemia-generated ROS also leads to the activation of atherogenic signaling pathways. Furthermore, hyperglycemia increases the number of free fatty acids, which change cell surface charges and structures. Therefore, epigenetic changes may be induced by hyperglycemia, indicating a possible mechanism of connection between glucose and neuropathy. Dr. Cooper concluded his talk by emphasizing the importance of metabolic karma and its effect on diabetes and health. Important studies in the future may probe for the role of transient hyperglycemic variability and transgenerational legacy from parents.
Oral Presentations: Obesity Pathogenesis and Treatment – Insights from Human Studies
Race Affects the Association of Obesity Measures with Insulin Sensitivity
Jeannie Tay, PhD (Nutrition Obesity Research Center, Birmingham, AL)
Research conducted by Dr. Jeannie Tay at the Nutrition Obesity Research Center underscores the importance of considering racial differences (in body composition, fat distribution, etc.) when evaluating risk for type 2 diabetes. One study sought to measure clamp-derived insulin sensitivity in 61 individuals without diabetes by measuring BMI, body composition, and fat distribution. The subcutaneous abdominal adipose tissue (SAAT), intra-abdominal adipose tissue (IAAT), intrahepatic fat (HF), total lean mass (LM), fat mass (FM), and leg fat (LF) were measured through MRI and DXA scans. Peripheral insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps. African Americans had 33% lower insulin sensitivity, higher SAAT, and higher LF vs. Caucasian Americans, even though all participants were in the same general risk cohort. For Caucasian Americans, higher BMI, FM, SAAT, LF, and HF correlated with lower insulin sensitivity. Overall, the results suggest that adipose measures represent stronger type 2 diabetes risk indicators in Caucasian Americans vs. African Americans. Most importantly, HCPs should take this into consideration when evaluating their patients for risk of obesity and type 2 diabetes. Dr. Tay alluded to future studies which might investigate differences between men and women in both African American and Caucasian populations. She also suggested that the study could be expanded to include other racial groups.
Oral Presentations: Translating Therapeutics to the Real World
Trends in Glycemic Medication and Control in Youths with Type 2 Diabetes (T2D): The SEARCH for Diabetes in Youth Study
Tongtong Wang, PhD (Merck, Kenilworth, New Jersey)
Dr. Tongtong Wang presented results from a post-hoc analysis examining medication at type 2 diabetes onset in younger patients, using data from the US SEARCH for Diabetes in Youth Study. The analysis drew from two primary sources: (i) a comparison of data from 646 patients who completed a SEARCH baseline visit in the 2002-2005 period and those who completed a visit in 2008-2012; and (ii) a longitudinal analysis of the 322 participants who also had a follow-up visit. In the first comparison, distribution of medications at baseline was largely comparable between those diagnosed in 2002-2005 vs. those diagnosed in 2008-2012: about two thirds of patients received metformin (65% in 2002-2005 vs. 70% in 2008-2012) and about one third received insulin at diagnosis (38% in both periods). Fortunately, the use of SUs was low in both periods, and even lower in the latter period though the difference is not significant (6% vs. 4%). Notably, the only medication with a significant difference in use between the two periods was TZDs – use of this class declined from 5% in 2002-2005 to 2% in 2008-2012 (p<0.05). While the overall use numbers are lower (since this study only examined first-line therapy), the drop in TZD use mirrors what we’ve seen in the overall type 2 diabetes population (from 2006 to 2013, TZD use overall dropped from 29% to 6%). It appears that A1c at baseline was a primary driver of the clinical decision to initiate metformin vs. insulin (which is expected, given the diabetes guidelines recommendations for those with high A1c at diagnosis): mean A1c at baseline was 6.4% in those on metformin monotherapy, 8.4% in those on insulin monotherapy (p<0.0001 vs. metformin monotherapy group), and 7.7% in those on insulin plus an oral diabetes drug (p<0.0001 vs. metformin monotherapy group). After an average follow-up of seven years, only 30% of those on just metformin at baseline remained on metformin monotherapy. 20% had added insulin therapy, 8% has switched entirely to insulin therapy, and 16% had added a second oral diabetes medication. Very notably, 27% of participants in this group were on no medications at follow-up. In the group taking insulin at baseline, 76% remained on insulin at follow-up. At follow-up, only 35% of participants achieved an A1c target <7%, including 44% of those on metformin monotherapy at baseline, 21% of those on insulin at baseline, and 65% of those who were not on any medications at baseline. The very low proportion of patients in this young population who were not at goal after seven years of follow-up is especially concerning and disheartening, given that these have a life expectancy of decades and could develop debilitating complications. We would’ve loved to see greater granularity on what proportion of these patients were initiated on GLP-1 agonists or DPP-4 inhibitors. SGLT-2 inhibitors were not yet available at the time the data in this analysis was collected, but we would’ve loved to see the impact of initial SGLT-2 inhibitor/metformin therapy on long-term glycemic control especially.
Oral Presentations: Diabetes in Pregnancy – The Tao to Understanding the Mechanisms (With Norbert Freinkel Award Lecture)
Norbert Freinkel Award Lecture
Grenot Desoye, MD (Medical University of Graz, Austria)
In this outstanding award lecture, Dr. Grenot Desoye explained that the human placenta is a friend to diabetes in late-stage pregnancy and a foe to diabetes in early-stage pregnancy. In early-stage pregnancy (week 6-week 12), women with type 1 diabetes will experience upregulation of MMP14, thereby increasing placental size. When the placenta grows, it increases oxidative stress in the uterine environment, stimulating a corresponding rise in insulin and glucose. As the placenta grows, the amount of glucose that can cross the membrane also decreases, and therefore the placenta is a foe in the early stages of pregnancy. In late-stage pregnancy, on the other hand, the placenta acts as a friend. In gestational diabetes, the placenta will hyper-vascularize to provide more oxygen to the fetus. It will also remove excess cholesterol to prevent atherosclerotic lesions. Although Dr. Desoye has conducted substantial research on the importance of the placenta in diabetes, he ended his lecture with a reminder that there is still much work to be done.
Does Time-in-Range Matter? Perspectives from People with Diabetes on the Success of Current Therapies and Drivers of Improved Outcomes (92-LB)
A Runge, L Kennedy, A Brown, A Dove, B Levine, S Koontz, V Iyengar, S Odeh, K Close, R Wood, and I Hirsch
A study – jointly authored by teams at The diaTribe Foundation, Close Concerns, and dQ&A – surveyed patients with type 1 and type 2 diabetes, emphasized the importance of time-in-range in patients’ daily lives – and how current therapies are not delivering on this metric. Results were collected by surveying members of the dQ&A Patient Panel, who were asked about the factors that have the greatest impact on their daily lives and potential drivers of improvement in mindset and diabetes management. The evaluation received responses from a remarkable 73% of those invited, totaling 3,461 people with type 1 and type 2 diabetes (n=1,026 and 2,435, respectively). Participants said that current therapies are coming up short in a number of areas, most notably in terms of helping patients achieve their desired time-in-range numbers, diet/exercise goals, and emotional well-being. Patients rated “time spent in the ideal blood glucose range” as having the biggest impact on their daily lives – even higher than the impact of A1c for type 1s (T1), type 2s on insulin (T2I), and type 2s not on insulin (T2NI) – but despite the importance placed on this metric, only 23% of T1, 25% of T2I, and 38% of T2NI reported that their current therapies are “very successful” at delivering in-range numbers (70-180 mg/dl). Similarly, a substantial proportion of patients (26% T1, 35% T2I, 50% T2NI) reported that a change in “diet and exercise” would have the biggest positive impact on their diabetes, likely resulting in a “big improvement” in their health. In spite of this, a minority of patients in each group (T1: 28%; T2I: 10%; and T2NI: 17%) said that their current therapies were “very successful” at “reaching, or keeping to, a healthy weight.” Finally, on psychological health, results showed that emotional well-being was disturbingly low across all three groups, with only a few patients rating therapies as “very successful” at achieving this outcome (22-34%). Taken together, these findings remind us that there is a significant need to more expansively evaluate what matters to patients and better align outcomes with patient priorities. We hope this work prompts future exploration of how such priorities can be incorporated into therapy development, regulatory decisions, and reimbursement. As a reminder, this data was presented in brief last year at the FDA Outcomes Beyond A1c Workshop, and The diaTribe Foundation will propel the conversation forward at another FDA workshop on July 21st in Bethesda, MD.
- These results underscore the need to consider the full spectrum of patients’ daily glycemia, rather than simply the average (as measured by HbA1c over a two-to-three month period). Time spent in ideal blood glucose range daily emerged as one of the top factors impacting the lives of individuals with diabetes. Not only does time-in-range correspond to successful outcomes of a particular therapy, but it also is a driver of positive mindset for individuals. As shown below, 54% of respondents with type 1 diabetes and 36% of respondents with type 2 diabetes on insulin ranked being in-range as the number one factor in establishing a positive mindset. Despite the large impact of time-in-range on improving daily quality of life, less than 50% of respondents reported that their current therapy was “very successful” at achieving positive time-in-range outcomes. Time-in-range is an indicator of therapy success and impacts the way individuals perceive their own management.
- Current therapies are not delivering sufficient diet and exercise guidance. Despite highlighting the “big impact” that time-in-range can have on daily life with diabetes, less than 50% of respondents reported their current therapy to be “very successful” at achieving positive time-in-range outcomes. Success scores were also low for current therapies’ success at preventing weight gain and allowing diet/exercise flexibility, suggesting that effective lifestyle modification strategies remain a major need for people with type 1 and type 2 diabetes. This is critical to us, as rates of obesity are increasing across all populations of people with diabetes.
- This study reveals key misalignment between the short-term factors that people with diabetes experience and how their management is evaluated by many healthcare providers, regulatory authorities, manufacturers, and payers. Respondents placed a high emphasis on factors such as food selection, hypo- and hyperglycemia, and weight loss, whereas the evaluation and prescription of therapies is based instead on longer-term factors such as HbA1c and the rate of hyperglycemia-induced complications. While decades of innovation have advanced certain aspects of diabetes management, the economic and human costs of diabetes remain high and therapies are still not succeeding on daily metrics that matter to people with diabetes.
We hope this work prompts future exploration of the outcomes that matter most to people with diabetes and how such priorities can be incorporated into therapy development, regulatory decisions, and reimbursement. For researchers and manufacturers, this means innovations should target measures such as psychosocial health, time-in-range (as measured by CGM), and behavior modification in addition to HbA1c. All stakeholders involved in research and product development could benefit from soliciting patient perspectives earlier and more frequently. This input should be incorporated on an ongoing basis and drive R&D priorities, regulatory risk-benefit decisions, and access.
One-Year Time Analysis in an Academic Diabetes CLinic (174-LB)
P Huynh, A Toulouse, and I Hirsch
This study found that an impressive 1,461 non-billable hours were spent per year to support one physician or advanced registered nurse practitioner (ARNP) in an academic diabetes care clinic. To conduct the analysis, clinic support staff at an academic diabetes clinic that sees 3,727 patients in 10,332 visits per year and employs 36 endocrinologist or ARNP full time employees catalogued time spent on phone calls, faxes, electronic chart messaging, and email for patient care during one month. One-month values were then extrapolated to one year. 1,945 triage interactions were recorded, lasting an average of 14.7 minutes. The main categories requiring non-billable interactions were medication issues (46% of interactions), health challenges (12%), hyperglycemia/hypoglycemia triage (8%), labs (5%) and coordination of care (5%). Overall, for every 1,264 face-to-face patient hours expended by a full-time physician or registered nurse practiioner per year, 1461 non face-to-face hours are spent by support staff. The authors conclude that this balance of incurring more non-billed than billed hours for diabetes care is not sustainable in the current healthcare landscape.
Symposium: Shared Decision-Making – Strategies for Improvements in Patient-Provider Communication
Shared Decision-Making – Diabetes Risk Perceptions and Prevention
Ann Albright, PhD (CDC, Atlanta, GA)
The legendary Dr. Ann Albright, director of the CDC’s Division of Diabetes Translation, provided invaluable insight into her approach to sharing information about diabetes risk prevention. Though she acknowledged that robust research on this subject is scarce, Dr. Albright emphasized that one thing is clear: “we need to address prevention to a much greater degree than we currently are” – hear hear! There is clearly a large role for policy and community-level strategies in the promotion of diabetes prevention, but in the context of one-on-one conversations in the physician’s office, Dr. Albirght’s take-home message was the need for greater sensitivity to which conversation topics are most needed for people at different levels of diabetes risk – low (general information about healthy behaviors), medium (NDEP resources and recipe guides), and high risk (structured programs like the DPP, or medication like metformin).
Shared Decision-Making – Why Does This Matter and What Do We Know
Linda Siminerio, PhD (University of Pittsburgh, PA)
Kicking off a lively morning symposium on the National Diabetes Education Program, Dr. Linda Siminerio (University of Pittsburgh Diabetes Institute, Pittsburgh, PA) underscored the importance of transitioning from traditional, paternalistic provider-driven decision-making to a more collaborative shared decision-making process. Illustrating the need for a change in the way that patients and providers typically communicate, Dr. Siminerio reviewed the results of an Institute of Medicine survey quantifying Americans’ beliefs, attitudes, and preferences about healthcare. The findings were striking: 80% of people want their healthcare provider to listen to them, but only 60% say it happens; less than half of people report that their provider asks about their personal health goals; and 90% of people want their healthcare providers to act as a team, and yet only 40% say it happens. Follow-up studies further illustrate the negative consequences that can emerge from an environment that doesn’t encourage shared decision-making; patients without decision support are 60% more likely to change their mind about a treatment plan, 23% more likely to delay a healthcare decision, five times more likely to regret their healthcare decisions, and 19% more likely to blame their physician for bad outcomes. Against this backdrop of the clear need for greater shared decision-making in clinical practice, Dr. Siminerio reminded the audience that barriers to shared decision-making are not easily overcome. Healthcare providers may find it a challenge to their autonomy and often find it difficult to communicate nuanced data to people without a medical background, whereas patients often suffer from health literacy challenges and a lack of useful decision aides. Kudos to Dr. Siminerio for being such an advocated for better communication – congratulations to her and her NDEP colleagues for a 20th anniversary! We look so forward to returning in our full report to share many other valuable talks from this session.
Shared Decision-Making – Goal Setting and Treatment Choices When Evidence Is Ambiguous
John Buse, MD (University of North Carolina, Chapel Hill, NC)
In a very heartfelt talk, the great Dr. John Buse provided expert advise on how to engage in shared decision-making with patients in circumstances where the clinical evidence is ambiguous. First and foremost, he advised the audience to "embrace the fact that most of what a patient wants to know is in fact unknown." He pointed out that indeed “we know the answers to nothing that’s important,” referencing the basic questions that patients ask him – How should I exercise? What should I eat? What drugs should I take? What A1c target should I pursue? And so on. Faced with this ambiguity, Dr. Buse offered the audience of healthcare providers the following tips for how to help patients find something that works for them:
- Embrace the question with praise.
- Find out what issues the patient is dealing with in the background. Dr. Buse wisely noted that it is critical to understand how an individual’s diabetes interfaces with their family life and work life especially. Understanding this is often key to identifying which kinds of treatment would best fit the person’s needs.
- Engage them. Speak openly with patients to resolve the question and identify specific actions to operationalize and evaluate their success in striving toward a treatment goal. Provide framing thoughts, but let this be a real discussion. Discuss process and timelines, and don’t hesitate to pusue more in depth expertise and opinions when necessary.
- Have information at hand to help guide deeper discussion and understanding. Dr. Buse noted that the same questions often come up again and again, so it is beneficial to have key resources at hand to discuss with patients (for him, one such resource is a “cheat sheet” outlining the pros and cons of various diabetes drugs).
- Encourage and motivate, but do not push patients (…at least at first).
- Avoid the temptation to provide the answer that works best for you. Dr. Buse urged the audience to always bear in mind that the patient is the one who has to live with these care decisions.
Shared Decision-Making and Vulnerable Populations – Social and Cultural Considerations
Monica Peek, MD (University of Chicago, IL)
Sharing her experiences on an increasingly important topic, Dr. Monica Peek addressed the social and cultural aspects of providing care and how to incorporate shared decision-making in underserved populations. Even though African Americans report wanting to participate as much in shared decision-making as their white peers, there are additional challenges for successful shared decision-making here because of race and perceived discrimination. Furthermore, there is a clear negative association between self-reported racial discrimination and healthcare and diabetes outcomes. In her research, Dr. Peek found that for diabetes complications, those reporting racial discrimination had twice the odds for retinopathy, half the odds for quality care measures like primary care, but no differences in self-care. Race can also impact the provision of shared decision-making, because it can negatively impact patient interactions for the patient and doctor (e.g. a patient believing the doctor assumed a paternalistic approach because of race). Barriers also include power imbalances, limited health literacy and self-efficacy in vulnerable populations, as well as mistrust, fear, and denial. Dr. Peek urged shared decision-making facilitators to engage and invite patients into the process, build strong interpersonal relationships, and validate health concerns. As an example, treatment adherence is a longtime frustration for physicians, but patients can view it as an empowering way to share in the decision-making process. She shared quotes from patients on adherence, with one saying “I didn’t tell [my doctor] about my preference for not messing with it… I just told her that I would go through with it”, or “I have a neighbor and she goes to the doctor, and when she gets medication she throws it in the garbage can”. Dr. Peek stressed that these behaviors are rational choices for patients to feel in control and urged providers to think about the complexities of what patients are internalizing. She then presented a case study on the Improving Diabetes program, which centers on patient empowerment with a discuss, debate, and decide model and includes culturally tailored education around shared decision-making like storytelling, community building, and video narratives. The program was able to lower mean A1c from 8.3% to 7.4% in a vulnerable Chicago population and create empowering patient videos that demonstrated how important communication and trust can be for shared decision-making in healthcare settings.
Shared Decision-Making “Then and Now” – Twenty Years of Diabetes Translation
Diane Tuncer (NIH, Bethesda, MD); Judith McDivitt, PhD (CDC, Atlanta, GA)
Founded in 1997 to promote shared decision-making, the National Diabetes Education Program (NDEP) is now celebrating 20 years of work. Ms. Tuncer and Dr. McDivitt overviewed the NDEP’s transitions since its inception – shifting focus to the wider population instead of exclusively middle-aged and olderAmericans, changing from promoting awareness of diabetes to now encouraging behavior change, and going from traditional mass media to embracing digital and social media as a way to reach patients. To keep up with the pace of change in research and a larger community, the NDEP is starting a diabetes blog in fall 2017 to promote clinical tips and more quickly share and translate insights in practice. The NDEP will also put a strong emphasis on motivating and supporting participants in the program, enrolling more patients, and participating in evidence based interventions to identify participants. Future priorities will also focus on healthcare disparities and to build new partnerships.
Symposium: ADA Education Recognition Program Symposium – Introduction to the 2017 National Standards for Diabetes Self-Management Education and Support
The Revised National Standards for Diabetes Self-Management Education and Support (Standards 1-5)
Joni Beck, PharmD (OU Medicine, Oklahoma, OK)
Dr. Joni Beck overviewed the revised National Standards for Diabetes Self-Management Education and Support (DSMES). As the co-chair for the 2017 workgroup, Dr. Beck led the process for the review and revision of the standard text for publication this fall. She emphasized how DSMES incorporates the needs, goals, and life experiences of the patient, and provides behavior, educational psychosocial, and clinical support. The major change in the 2017 Standard is moving from a description of DSMES programs to instead a description of DSMES services, to reflect how DSMES is individualized and not a scripted program for everyone. Next steps will be for the ADA and AADE to adapt their interpretive guidance to reflect the new revised Standards and Medicare must approve both. However, reimbursement does not define the Standards, and DSMES reimbursement varies greatly by payer. Below we outline Standards 1-5 of the revised DSMES Standards:
- Standard 1 – Internal Structure: The providers of DSMES services will define and document a mission statement and goals. The DSMES services need organizational support and defined leadership and lines of communication as the key to successful entities.
- Standard 2 – Stakeholder Input: The providers of DSMES will seek ongoing input from valued stakeholders and experts to promote quality and enhance participant utilization.
- Standard 3 – Evaluation for Population Served: Providers will evaluate the communities they serve to determine the resources, design, and delivery methods that will align with the community. They will identify barriers that prevent access to DSMES and can use technology to address these barriers.
- Standard 4 – Quality Coordinator Overseeing DSMES Services: A quality coordinator will be designated to ensure implementation for the Standards and oversee the process. The coordinator is responsible for all components of DMES including evidence based practice, service design, evaluation and quality improvement.
- Standard 5 – DSMES Team: At least one of the team members will be a registered nurse or dietitian, nutritionist, pharmacist with training in DSMES, or another health care provider like a CDE or BC-ADM. Other providers may contribute to DSMES with appropriate training and with supervision and support by at least one of the team members listed above.
The Revised National Standards for Diabetes Self-Management Education and Support (Standards 6-10)
Deborah Greenwood, PhD (Georgetown University School of Medicine, Hyattsville, MD)
Dr. Greenwood gave an empowering talk on the Diabetes Self-Management Education and Support (DSMES) Standards, calling for greater individualization of DSMES, using technology to communicate with and empower patients, and using quality measures and metrics to improve the delivery of DSMES. She emphasized that the key is creating an individual education plan for participant need, not a set-in-stone curriculum. She emphasized that DSMES is an ongoing lifelong process and no participant is required to complete a set DSMES structure or program. Providers can also help people to navigate the health care system by learning advocacy and e-health education skills in times of healthcare change. Technology-enabled DSMES is particularly promising for the ability to use text/SMS, apps, and social media to empower and enable patients and potentially improve clinical outcomes like A1c through a feedback loop with two-way communication, better analysis of data, and customized feedback (although this is currently not reimbursable by Medicare). Notably, Dr. Greenwood cited the importance of patient empowerment and recommended resources on the AADE website on online diabetes communities and encouraged the audience to experiment and learn to see the value in the online community. Below we outline Standards 6-10 of the revised DSMES Standards:
- Standard 6 – Curriculum: DSMES curriculum should reflect current evidence practice guidelines and emphasize behavior change, individualization, and AADE7 Self-Care Behaviors.
- Standard 7 – Individualization: DSMES needs will be identified and led by the participant with support from team members to develop an individualized DSMES plan. The Standard used to use the word “collaborative” but has now changed to “led” by participant. Person-centered care focuses on the priorities and values of individual, which can include the disease and treatment burden, need for peer support, and providing support during key points like during diagnosis, the annual checkup, times of complications, or transitions in care. Providers should use interactive teaching styles and not static lectures, incorporate patient generated health data, use principles from cognitive behavioral therapy, participate in shared decision making, use clear health communication principles, and incorporate validated assessment tools to evaluate process.
- Standard 8 – Ongoing Support: Participants will be made aware of options and resources available for ongoing skills, knowledge, behavior change for diabetes management and strategies available for ongoing support within and outside of DSMES. 99% of diabetes is self-management so any tools that can help include peer support using social networking sites or online diabetes communities.
- Standard 9 – Participant progress: Providers will monitor and communicate whether participants are achieving their personal diabetes self-management goals and other outcomes to evaluate the effectiveness of interventions. Providers need to focus on goal-setting strategies to meet a patient’s personal targets and use SMART goals to achieve behavior change. Self-management needs goal setting and adding content, not just pushing out content. Individual outcomes like clinical improvement, quality of life, and satisfaction should be tracked.
- Standard 10 – Outcome and Process: There should be a plan to conduct system evaluations on process and outcome data, measure the impact and effectiveness of DSMES services through continuous quality improvement plan. The emphasis on quality addresses trends through MACRA to shift provider payment from productivity to quality and outcomes and track several measures of behavioral, clinical, and operational success.
Symposium: ADA Diabetes Care Symposium – Diabetes Care and Research Through the Ages
A Look Back as to How We Got Here
Jay Skyler, MD (University of Miami, FL)
Dr. Jay Skyler opened this symposium with a quick tour through the history of diabetes diagnosis and management, beginning back in 1500 BC with the earliest known record of diabetes. He noted that diabetes was a global problem in ancient times as it is today, with references to “sweet urine” noted in societies throughout the world. The terminology evolved over time – the disease was described as “pissing evil” by at least one figure in the 1600s and the word “mellitus” was first added in 1797. Dr. Skyler recognized Apollinaire Bouchardat as the “father of diabetology,” given that he introduced exercise and daily urine testing as part of treatment and was the first of many to insist on individualized approaches to diabetes management. Before the discovery of insulin, Dr. Skyler described treatment of diabetes as consisting mainly of semi-starvation and various ineffective medications including opium. In the 19th century, attention shifted to the pancreas, as a number of investigators deduced that it was the organ responsible for regulating glucose. Dr. Skyler acknowledged the revolutionary extraction of insulin by Banting and Best in 1921, and emphasized that their ability to collaborate with Eli Lilly to mass produce the substance was as important as the discovery itself. As for oral medications, Dr. Skyler recounted the discovery of sulfonylureas and the now-famous (or infamous) long process of bringing metformin to the US.
What Does the Future Hold?
Ele Ferrannini, MD (University of Pisa, Italy)
The great Dr. Ele Ferrannini offered his perspective on the value and relative speed of development in current major areas of research focus within diabetes. Overall, he foresees the greatest value in organ-level research into the role of the heart, kidney, and brain in diabetes pathophysiology, ranking this area a 9/10 in terms of value. Tissue-level research (into beta-cell plasticity, adipose tissue plasticity, and gut factors including the microbiome) also ranked highly in terms for value for Dr. Ferrannini – a 7/10. Pharmacology (new drugs and new treatment strategies) and genome level research (genetics, epigenetics, and “omics”) received a modest but respectable 6/10 value ranking. On the other hand, Dr. Ferrannini was much less optimistic about the value of environment-level research (diet/exercise, toxic environmental factors, and infections; an overall 3 ranking) and was particularly pessimistic about information technology research (including sensors, electronic health records, and big data). Information technology received a 2/10 value assessment from Dr. Ferrannini, though he noted that this is the fastest and most active area of development within his list – in terms of speed, information technology scored a 9/10 on his scale. Indeed, the speed of development in this area underscores that massive interest and value many in diabetes and the broader healthcare field see in digital health – which made Dr. Ferrannini’s pessimism all the more surprising. As he put it, the concept of precision medicine – powered by massive amounts of population-level health data – has gone “viral.” In his view, this focus on gathering large amounts of health data and mining it for insights has flipped the traditional model of medical research, which traditionally has focused on the generation of hypotheses and use of clinical data to evaluate the validity of a priori hypotheses. As a clinical trial purist, Dr. Ferrannini’s stance doesn’t surprise us, though we do think there’s value in generating insights from population-level data that would have been near-impossible (and extremely costly) to arrive at through randomized, controlled trials. We certainly think there’s room for both kinds of studies in science and medicine!
- Taking the impact of sensors and big data one step further, Dr. Ferrannini cautioned that the drive toward digital could fundamentally change the doctor-patient relationship in a negative way. Dr. Ferrannini characterized the current model of healthcare as one in which (i) the patient feels unwell; (ii) the patient visits the doctor; (iii) the doctor assesses the patient’s symptoms, history, etc.; and (iv) the doctor provides advice based on his or her knowledge and expertise. In the near future, however, Dr. Ferrannini forecasted the patient visit could be replaced by health data generated through sensors (CGM, blood pressure monitors, etc.) and the doctor could be replaced by a clinical decision-making app. Further in the future, he suggested that patients could be replaced by anonymous ID numbers, in order to better collect their information for “big data” repositories. Ultimately, Dr. Ferrannini suggested that the healthcare system will fundamentally change to “feed this black hole of big data.” Further, he pointed out that a key consideration will be who “owns” each big data repository and how they might use and manipulate the data. While Dr. Ferrannini’s concerns are well-taken (and the high value he places on the doctor-patient relationship underscores what an incredible clinician he is), we would love to learn more about his views. At the current time, feel he may have a bit of an extreme, doomsday-scenario view of digital health. In certain cases, telemedicine, clinical decision support, and other tools can help support increasingly busy physicians, expanding their capacity to serve more patients and focus their energies on the most complex cases. Further, the use of sensors and centralized collection and interpretation of individual health data plays an important role in empowering and engaging patients in their diabetes or broader health care. While some thoughtfulness is clearly warranted on how best to use the wealth of data that we now have the ability to collect (so as not to fall prey to information overload), we continue to believe that digital health represents an immense opportunity for the diabetes and healthcare fields.
- Dr. Ferrannini also highlighted pharmacology as a relatively fast area of research, scoring a 7/10 on his scale. Organ- and tissue-level research scored a modest 5/10 for speed, while genome-level research scored a 4 and environment research scored a 3.
Presentation of “Profiles in Progress” Plaques
William Cefalu, MD (ADA, Alexandria, VA)
ADA Chief Scientific and Medical Officer Dr. William Cefalu presented four “profiles in progress” awards to honor those who have made long-lasting contributions to the diabetes field. The first three recipients fit the usual mold of iconic researchers and educators, while the fourth recipient undoubtedly had an enormous personal impact on many adults living with diabetes today. Dr. Richard Rubin was recognized for his ability to incorporate behavioral science into diabetes treatment and his early advocacy of personalized diabetes care. Dr. Harold Lebovitz was honored as a “stalwart of diabetes research, care, and education” and one of the most influential voices on diabetes management strategies. Dr. George Bray was lauded for his substantial contributions on the pathogenesis and mechanisms of obesity and his landmark clinical studies on weight loss with lifestyle interventions. The fourth award was given posthumously to actress Mary Tyler Moore in recognition of her longtime advocacy on behalf of patients with type 1 diabetes like herself. Accepting the award on her behalf, her husband Robert Levine delivered a passionate call for more urgency and creativity in the search for a cure. As he put it, “the reality is that we have yet to deliver on key promises: finding a cure, ending suffering, and protecting futures.”
Symposium: Emerging Therapeutic Targets and Mechanisms of Action
How Should We Think about the Role of the Brain in Glucose Homeostasis and Diabetes?
Michael Schwartz, MD (University of Washington, Seattle, WA)
Dr. Michael Schwartz discussed the role of the brain in glucose homeostasis, emphasizing that the brain is involved in establishing the biologically defended level of glycemia. With this hypothesis, Dr. Schwartz presented data of brain-specific Glut2 KO mice, demonstrating that this phenotype led to impaired CNS glucose sensing with progressive deterioration of both beta cell function and glycemic control. Additionally, he pointed to the data surrounding type 2 diabetes and Alzheimer’s disease, highlighting that the comorbid conditions’ neurodegeneration likely affects glucoregulatory neurocircuits, which raises the defended level of blood glucose. Dr. Schwartz continued by exploring how pancreatic beta cells respond to insulin resistance, noting that beta cell compensation for insulin resistance involves increased responsiveness to glucose rather than elevated blood glucose. He shared that coupling of insulin secretion to insulin sensitivity to meet evolving needs for glucose utilization also appears to contribute to the brain’s effect of establishing a set glycemic level. Thus, looking at the type 2 diabetes pathology as defective neuronal glucose sensing, Dr. Schwartz closed by highlighting that there may be an emerging role for brain-directed therapeutic strategies. Specifically, such therapies can help normalize the defended level of glycemia rather than follow the current therapeutic strategy of simply dropping glucose below its defended level on a day-to-day basis. Over the past several years, we have certainly seen increasing attention to the brain’s role within metabolic health and Dr. Schwartz’ latest work highlights it as a promising and sustainable area regarding therapeutics – please see our interview with Dr. Schwartz and our coverage of his impressive Nature publication for more on his research on the brain within diabetes and obesity.
Questions and Answers
Q: Do you care to postulate why people in the South have higher tendencies to develop diabetes? Is it due to temperature or just due to culture?
A: I don’t think anyone knows. When you become really obese, your hypothalamus undergoes an inflammatory state. There’s a glial response. That type of mechanism could explain why you have an impairment related to blood glucose levels. This is associated with diet and obesity. So we don’t know what causes it. As for whatever’s going on with insulin resistance and islet function, there’s probably also an underlying CNS problem. Are there differences in populations? I’d love to know that.
Q: Exercise is also a potent means of improving glycemic control and increased peripheral insulin sensitivity. Can exercise also improve brain’s ability to sense blood glucose?
A: I don’t think that’s been looked at. The only data I’m aware of is that exercise increases CNS leptin sensitivity. The problem with the field is that we know so little about how blood glucose sensing works and how to measure it. In order to answer your question, we need a sophisticated way to measure these variables.
Q: What are your thoughts on FGF-1 vs. FGF-21?
A: FGF-1 targets all FGF-1 receptors and FGF-21 does not. FGF-21 appears to require a co-factor at the site of the receptor in order to work. FGF-1 does not. My sense is that FGF-1 has a population of targets in brain that are not touched by FGF-21.
Symposium: Global Therapeutic Challenges and Solutions in Diabetes Care
Improving Access to Insulin in Developing Countries
David Beran, PhD (University of Geneva, Geneva, Switzerland)
In a wide-ranging talk, Dr. David Beran addressed the current state of insulin access in developing countries, analyzing how insulin is produced and distributed from a global perspective, and overviewing lessons from other patient movements on how to increase insulin access and change the status quo around insulin prices. Developing countries tend to have low expenditures on health while also facing epidemiological transitions at a dramatic rate. The highest increase in diabetes will be in low and middle-income countries, especially southeast Asia and Africa, with about 200,000 children aged 0-14 years old in these countries being diagnosed with type 1 diabetes. The ACCISS study found that the insulin market in 2012 is $20.8 billion and dominated by three large multinational companies (Eli Lilly, Sanofi, and Novo Nordisk, which hold 99% of the value, 96% volume, and 88% product registrations). There are 39 smaller insulin manufacturers but 23 only sell in one country, and 10 countries make up 98-99% of global value of retail insulin exports from 2004-2013. This asymmetry is not an intellectual property issue, as there are no patents on any formulations for human insulin, and patents on analogue insulins already on the market in the US and Canada have expired or will soon expire. From a global perspective of insulin use, high and upper middle income countries have decent uptake of analogue insulins, where lower middle income and low income have low use of analogues and have used animal insulin for a much longer time. The major question Dr. Beran posed was whether the money being spent on analogue insulin is worthwhile compared to other ways that money could be used. Currently, several programs are working to improve insulin access through company initiatives, IDF Life for a Child, and Insulin for Life by World Health Organization, but none are sustainable or really change the status quo. Dr. Beran applauded the ADA for the Stand Up for Affordable Insulin and discussed ways to learn from the HIV/AIDS movement on how to change the status quo. He identified the need to gain support from civil society, ask national governments to recognize access to insulin, move beyond self interest and change stigma, fund innovation and ensure access to innovations, private sector innovation, and to ask researchers to document challenges and target research to specific needs for underserved populations. The US invested $19 billion for AIDS in low and middle-income countries, which has dramatically increased the number of people treated. Compared to this, Yudhkin estimated in 2000 that the US could invest $3-5 million to provide insulin for children in low and middle-income countries. He ended the presentation with a powerful call to action, pointing to 2021 as the insulin centenary and asking the audience to remember those with type 1 diabetes living in developing countries
Diabetes Care in Resource Constrained Settings
Akihiro Seita, MD (United Nations Relief and Works Agency, Amman, Jordan)
Dr. Akihiro Seita discussed the growing issue of diabetes care in the refugee population. Dr. Seita opened his talk by reminded the audience that refugees are not a number and are merely citizens who have become refugees because of global conflicts outside of their control. There are 26.5 million refugees in the world, with most coming from historical Palestine, Syria, Afghanistan, Somalia, and South Sudan. The top six countries that accept refugees are Jordan, Turkey, Palestine, Pakistan, Lebanon, and Iran, making it fitting that Dr. Seita’s focus is on Palestinian refugees living in vulnerable conditions in Jordan. Diabetes and hypertension have been increasing steadily among Palestinian refugees, and UNRWA’s diabetes care provides NCD clinic for diabetes care in all health centers with diagnosis and treatment provided free of charge and with health education and health information systems available. After a clinical audit, the United Nations Relief and Works Agency (UNRWA) found that diagnosis, treatment, and staff are meeting the necessary standards but there was a lack of widespread A1c testing as well as extensive obesity in the population (90% in women). Dr. Seita worked on e-health to make EMR available at 120 healthcare centers and created more than 3 million patient records. His group also created healthy lifestyle campaigns with cooking classes, education programs, and exercise. The program was successful in providing stable primary health care service delivery, giving integrated and sustainable diabetes care, using committed staff, providing a regular supply of medicines, and creating innovations in family health team and e-health with partnerships, a cookbook and an NCD handbook. However, challenges remain for the program: medication costs continue to increase, as has patient load, and overall costs for diabetes and hypertension alone account for 46% of medicine expenditures. Insulin is the single most costly medicine they provide, and while services are covered, glycemic control is still difficult (only 28% of patients have A1c <7%). Furthermore there is limited care for complicated conditions that require specialists or hospitals and prevention is limited because of factors outside of UNRWA’s control such as the determinants of health (e.g. sale of sugar and tobacco). This was an inspiring but sobering case study on the feasibility of providing comprehensive diabetes care in a refugee setting and an important call to better understand the social determinants of health such as disability, loss of social support, and increased vulnerability due to social change that are seen with refugees. Importantly, diabetes is an important issue to address for 21st century refugees, and there can be no humanitarian assistance without diabetes care.
Symposium: Diabetes Care for Older Adults
Hypoglycemia in the Older Patient with Type 1 Diabetes
Ruth Weinstock, MD (SUNY Upstate Medical University, Syracuse, NY)
Faced with studying hypoglycemia risk in older populations with type 1 diabetes, Dr. Ruth Weinstock admitted that there is very limited data available. Most of her presentation focused on data from the T1D Exchange and smaller trials, and she emphasized how multiple trials have shown that A1c is not the full picture when it comes to evaluating hypoglycemia. Glucose variability may be a better measure for glycemic control in older adults. However, using glycemic variability as a reliable metric will require more accurate CGM data, trials demonstrating the benefit of CGM use in older adults (hopefully coming soon in the WISDM study), and integration of data into the EMR. Dr. Weinstock advocated for CGM in older patients with type 1 diabetes because it can be an effective strategy to minimize the risk of hypoglycemia. Although raising the A1c goal in older adults may help decrease rates of hypoglycemia, it does not prevent the complication, and other strategies are necessary to fully address the dangers of hypoglycemia in the older patient with type 1 diabetes.
- The T1D Exchange Severe Hypoglycemia in Older Adults with Type 1 Diabetes Study suggests that A1c is not a good predictor for hypoglycemia risk. The study featured a case-control design that compared older patients who had experienced severe hypoglycemia in the past 12 months vs. those self-reporting no severe hypoglycemia events in the past three years. The study assessed glucose levels in 201 participants with blinded CGM for 14 days, and found no difference in A1c, mean glucose, or time-in-range between people in the severe hypo vs. no severe hypo arms. Notably, the key difference was glucose variability, where patients experiencing hypoglycemia episodes also had high glucose variability. This cohort also had higher rates of hypoglycemia unawareness, higher scores on the hypoglycemia fear survey, and poorer performance on tests of general mental status, processing speed, and executive functioning.
- The WISDM study, run by the T1D Exchange, the Helmsley Foundation, and JDRF, will be the first randomized trial of CGM use in older type 1 adults. Dr. Weinstock and audience members were massively excited about the potential for CGM use to reduce hypoglycemia. She discussed how older adults with type 1 could benefit from professional CGM to detect unrecognized hypoglycemia, while patients struggling with hypoglycemia unawareness, frequent hypoglycemia, or high glucose variability could find personal CGM helpful. Features such as communication using remote monitors or sharing features are also important tools for older adults.
- Dr. Weinstock suggested several management strategies in older adults with type 1. She called on CGM designers to consider features helpful to an older population – louder alarms, larger fonts, more contrast on displays, minimizing alarm fatigue, and preventing data overload that can feel particularly overwhelming for older adults. She expressed optimism for low glucose threshold suspend and for hybrid systems. Dr. Weinstock also suggested other management strategies like selecting insulin analogs with less risk of hypoglycemia, simplifying regimens when possible, and increasing screening for cognitive, vision, and hearing impairments.
Benefits and Harms of More Aggressive Glycemic Treatment in Older Adults
M. Sue Kirkman, MD (University of North Carolina, Chapel Hill, NC)
Dr. Sue Kirkman presented a talk prepared by Dr. Medha Munshi, which reviewed the pros and cons of intensive glucose control in older adults with diabetes. She discussed current paradigms of management and outlined a treatment algorithm for how to optimize benefits and minimize harm. Older adults with diabetes are a particularly heterogeneous population with different durations of diabetes, functional status, life expectancy, comorbidities, and living situations that impact their optimal treatment plan. In this patient population, Dr. Kirkman argued that many of the benefits of intensive management are given less mental weight, whereas harms seem much more immediate in terms of increased risk for hypoglycemia, higher costs, and greater treatment burden for patients. While there is limited data on the treatment of older populations specifically and much of treatment is based on expert opinion, appropriate goal-setting should focus on a glycemic strategy and not just a numeric goal. A1c is not the complete picture and needs to be supplemented with an understanding of the patient’s social support, hypoglycemia risk, living situation, and life expectancy. Overall, Dr. Kirkman advocated for incorporating these factors into an individualized glycemic strategy for older patients that can minimize the rate of hypoglycemia. She also pushed for using glycemic variability instead of A1c as a better tool to evaluate glucose management, and we love this idea.
- Dr. Kirkman presented a framework of how to think about glycemic goals, with treatment recommendations based on patient characteristics and health status. Patients who benefit the most from intensive control are younger, have a shorter duration of diabetes, have no macrovascular or microvascular complications, have low comorbidities, better health, and a longer life expectancy, while patients most at risk of hypoglycemia and adverse events from intensive control tend to be older and frail, have a long duration of diabetes, already have macrovascular or microvascular complications, have comorbidities, or are unable to follow a more complex regime.
- A1c is an average and should not be used as the only parameter of management, particularly in older adults. A1c is affected by variables like age and race, and by conditions that are more common in older patients like anemia, recent infection, transfusion, hemodialysis, erythropoietin therapy, uremia, or anemia of chronic disease. Moreover, CGM tracings of patients with type 2 diabetes display huge differences in time spent in hypoglycemia even with the same A1c, again pointing to the heterogeneity of the elderly diabetes patient population.
- There are limited data on the benefits of intensive glucose control in older patients with diabetes. DCCT and UKPDS excluded adults >65 years old, so it wasn’t until ACCORD, ADVANCE, and VADT that there was data on elderly patients. These more recent studies all showed increased microvascular benefit with no CV benefit in older adults randomized to intensive control, and ACCORD found increased mortality in the intensive treatment arm. However, these trials still didn’t include frail older patients or those with cognitive impairment. There were higher rates of severe hypoglycemia in older patients in both arms of ACCORD.
- There is evidence that older patients are currently being over-treated in their diabetes management. Dr. Kirkman presented several studies that examined older patients in complex or poor health who were still being managed intensively, where ~50% had an A1c <7% and 60% were on sulfonylureas or insulin, which suggests overtreatment and the risk of hypoglycemia without additional benefit. An Optum study in the US also found that only ~24% of frail patients with an A1c <6% had their treatment de-intensified. This intensive regime is still used despite Medicare data that shows hypoglycemia in type 1 and type 2 diabetes is a huge harm that causes more emergency department admissions than hyperglycemia. In our view, this seems like a cry for better patient education on managing hypoglycemia risk, since we don’t want to discourage anyone from reaching their A1c goal out of fear of hypoglycemia.
Symposium: Cognitive Functioning and Decision-Making in Diabetes
Long-Term Impact of a Lifestyle Intervention on Cognitive Outcomes among Individuals with Diabetes – Findings from Look AHEAD
Mark Espeland, PhD (Wake Forest School of Medicine, Winstom-Salem, NC)
Dr. Mark Espeland presented cognitive outcomes data of Look AHEAD participants, demonstrating that intensive lifestyle intervention in “mid-life” may result in less cerebrovascular disease and brain atrophy as well as better late-life cognitive function in certain populations. Dr. Espeland opened by walking attendees through the design and methods of the Look AHEAD trial and prefaced the discussion by noting the increased risk of dementia associated with type 2 diabetes and obesity. Turning to the results, he showed that, compared to a control condition, 10-years of lifestyle intervention in individuals with BMIs <30 kg/m2 was associated with better cognitive function, while for those with BMI ≥30 kg/m2 it was associated with slightly worse cognitive function. While the intervention had no overall impact on the prevalence of cognitive impairment (p=0.93), there was a similar trend for reductions among individuals who were not obese, but increased prevalence among those who were most heavy. Notably across BMI groups, intensive lifestyle intervention was associated with significant benefits on markers of brain atrophy and cerebrovascular disease. Compared to the control group, the lifestyle group had less ischemic lesion volume (1.86 cc vs. 2.49 cc, p<0.03) and greater cerebral blood flow. Exploring mechanisms for these differences, Dr. Espeland mentioned the possibility of that the intervention altered neurovascular response, cardiac output, or brain energy metabolism. In conclusion, Dr. Espeland highlighted the various benefits (i.e. cognitive function, cerebral blood flow) shown in patient populations who are “not too heavy” but noted that those that are “very heavy” can interestingly experience slightly worse late-life cognitive function with intensive lifestyle interventions – an area of personalized medicine that we believe will certainly prompt further research. As discussion of neurodegenerative disorders in the context of diabetes and obesity grows, we see the brain’s role and cognitive outcomes becoming an increasingly hot topic in the field.
Questions and Answers
Q: I would guess that the heavier group has a higher likelihood of having sleep apnea. Did you check if the groups had a difference in that comorbidity? So with more sleep apnea, you’d expect more dementia?
A: An ancillary study to Look AHEAD showed that the lifestyle intervention reduced the prevalence of sleep apnea. This might be expected to benefit cognitive function, but we haven’t yet examined how the sleep data correlate with the cognitive data, so that’s a great area to explore.
Q: I’m wondering about the legacy effects of cardiovascular disease – if the heavier participants didn’t benefit as much due to their lifetime exposure to excess body weight? If you’ve had a BMI of 40, you were likely overweight at an earlier time in life.
A: What you’re pointing out is that there may be a window of opportunity for lifestyle intervention to prevent cognitive decline. It’s very possible that some of these individuals might have been too far down the neurodegenerative pathway for lifestyle intervention to provide benefit.
What Is Shared Decision Making and How Can It Improve Diabetes Care?
Kellie Rodriguez (UT Southwestern Medical Center, Dallas, TX)
Ms. Kellie Rodriguez (UT Southwestern Medical Center, TX) shared compelling evidence encouraging healthcare providers to engage their patients in shared decision making. She defined shared decision making as closely discussing clinical decisions, medication, and management, with a focus on extending the conversation way beyond risks and benefits to more important considerations such as patient preferences and values. She also detailed the need to keep patients' lived worlds in mind, highlighting that sometimes the best patient decision is sometimes different than what would be the best decision on purely clinical terms. From her perspective, optimal diabetes management is driven by an interdisciplinary team with the patient as the captain. In order for patients to become equal players on this team, education will be critical. Shared decision making tools offer a promising solution: the latest Cochrane review analyzed 105 studies comprised of 31,043 patients and determined that implementation of decision aids can lead to improved knowledge, more informed choices, higher participation in decision making, and, most importantly, greater satisfaction. However, employment of shared decision making is not without its challenges. While the review indicated that more research is needed to address efficacy with lower literacy populations, Ms. Rodriguez discussed one study conducted in 2013 showing improved decisional, but not clinical, outcomes in nonacademic and rural communities when decision aids were provided. Still, Ms. Rodriguez reported several barriers, including limited research evidence for clinical effectiveness, a lack of providers with the necessary skills and/or interest, and difficulties meeting diverse cultural needs – not to mention the additional cost and time. At this point, the tools have been developed and the greatest opportunity and responsibility, Ms. Rodriguez claims, lies in establishing the support required to effectively implement these chosen decisions. We hope that research continues to probe these problem areas, addressing the ways in which we can improve both patient and provider engagement moving forward.
Cognitive Functioning in Youth with Diabetes – Implications for Improving Diabetes Management
Cynthia Berg, PhD (University of Utah, Salt Lake City, UT)
Dr. Cynthia Berg stressed the importance of high executive functioning in diabetes management, especially in children and adolescents with type 1 diabetes. Diabetes puts a lot of responsibility on patients every day: dosing insulin, monitoring blood glucose, being wary of hyper or hypoglycemia, scheduling regular checkups with an endocrinologist or diabetes care provider, etc. For youth and adolescents, these tasks may be especially difficult. Cognitive functioning during transitional stages of life (before puberty, between high school and college, etc.) can be compromised in diabetes. Executive functioning is critical to maintain patient engagement. Studies indicate that lower IQ correlates with higher A1c. Youth with limited or compromised executive functioning are more prone to error in medication planning, following up with their provider, or other aspects of diabetes management. At the core of her talk, Dr. Berg emphasized that changes should be made in the treatment plan for these patients to offer additional support in chronic disease management.
Symposium: Pediatric Diabetes and Associated Comorbidities
Mental Health Comorbidities in Type 2 Diabetes—The Not-So Hidden Iceberg
Diana Naranjo, PhD (Stanford University, Stanford, CA)
Dr. Diana Naranjo of Stanford University discussed how mental health problems often accompany type 2 diabetes in youth, suggesting that these must be anticipated and managed from the onset of diabetes diagnosis. Youth with type 2 diabetes are at increased risk (relative to both youth with type 1 diabetes and counterparts without chronic disease) for depressed mood, concerns of isolation, and bullying. Psychosocial risks include psychological and behavioral risks like depression and disordered eating, family risks like conflict and miscarried helping, as well as environmental and systems disparities like poverty and lower socioeconomic status, race, insurance, and access to healthcare. Obesity and binge eating are also associated with type 2 diabetes and challenges with managing this can additionally lead to feelings of inadequacy. These considerations are especially significant in light of the dramatically increasing prevalence of type 2 diabetes in youth – the SEARCH for Diabetes in Youth Study projects up to a 4-fold increase in youth-onset type 2 diabetes by 2050. Dr. Naranjo closed with a case study about a 16-year-old Latino boy struggling to manage his type 2 diabetes, using this as a backdrop to highlight strategies to overcome barriers and reinforce healthy habits.
- Binge eating in youth is an important predictor of type 2 diabetes. Youth with clinical binge eating disorder are more likely to develop obesity and depression in addition to type 2 diabetes, and tend to have lower quality of life. Dr. Naranjo believes that reported binge eating might represent an early behavioral marker upon which to focus interventions for obesity and metabolic syndrome, especially since these behaviors in youth are associated with higher risk for other health complications including kidney disease, nerve disease, eye disease, and heart disease, hypertension, and retinopathy.
- Dr. Naranjo elucidated challenges to type 2 diabetes management that can lead to feelings of frustration and loss of control, as well as worries for the future. These barriers to managing type 2 diabetes include very demanding treatment regimes, stigma and shame, psychological distress, intergenerational burden of type 2 diabetes, financial barriers minimizing access to diabetes care, sharing of insulin prescriptions, and cross-cultural considerations.
- Though few effective treatments for type 2 diabetes and depression in youth currently exist, Dr. Naranjo is optimistic about prevention efforts in this space. She expressed particular enthusiasm for the potential of cognitive behavior therapy approaches to improve mindset, and we hope to see more data on this in the future. Indeed, the unmet need for the care of psychological comorbidities of diabetes is particularly stark in young people, and we are appreciative that it is finally beginning to receive some attention.
Symposium: DA Diabetes Symposium – Emerging Therapeutic Targets and Mechanisms of Action
Mining the Genome for Therapeutic Targets
Jose Florez, MD (Massachusetts General Hospital, Boston, MA)
Dr. Jose Florez argued that an increased understanding of genetics will eventually allow clinicians to make more targeted decisions about drugs and therapies to pursue for the treatment of diabetes. He explained that diabetes, type 2 in particular, is a heterogeneous disease best understood as a syndrome encapsulating multiple forms of insulin resistance – a topic he elaborated on more broadly at last year's ADA. Dr. Florez believes the next era of diabetes treatment will involve a personalized approach that addresses the subtypes of the patients’ diagnosis, in a manner similar to how oncologists treat patients with cancer. He then shifted to an encompassing discussion of how researchers can use genetic markers to help target their research by: stratifying populations to target, implicating metabolic pathways, identifying molecular targets, clarifying the direction of the effect, establishing causal inference and exploring off target consequences earlier in the development process. As part of this, he highlighted the Accelerating Medicines Partnership Type 2 Diabetes Knowledge Portal, a database of data around human genetic information linked to type 2 diabetes and related traits, as a resource for researchers to understand existing research on a then ask if a particular gene they are interested in.
- Stratifying patients by population is a broad way to predict risk for type 2 diabetes and select more targeted treatments. Dr. Florez cited the example of a high-risk variant of the TBC1D4 gene, which is present in about one fifth of the Inuit population in Greenland. Individuals with this genetic variant tend to have higher concentrations of plasma glucose and serum insulin two hours after oral glucose and lower concentrations of fasting plasma glucose when compared to individuals with other genotypes. Based on this information, Dr. Florez noted that clinicians caring for patients from the Inuit population may want to use an oral glucose tolerance test OGTT for diagnosis, and insulin sensitizers for therapy.
- Dr. Florez also argued that a deeper genetics understanding will not only help identify future drug targets, but will also help build a deeper sense of the nuances and exceptions within those new drug classes. He used the example of SLC30A8, a gene that encodes the zinc transporter ZnT8, which is needed for proper insulin processing, storage and secretions. While a common missense variant in SLC30A8 is known to raise type 2 diabetes risk, further research has also uncovered a less common loss-of function variant which has been proved to protect against the development of type 2 diabetes.
Symposium: Can “Omic” and Genome-Wide Association Studies (GWAS) Reveal Therapeutic Links between Type 1 and Type 2 Diabetes?
Metabolomic Links between Type 1 and Type 2 Diabetes
Flemming Pociot, MD (Herlev-Gentofte Hospital, Hellerup, Denmark)
Dr. Flemming Pociot highlighted the metabolomic links between type 1 and type 2 diabetes, underscoring the potential of this field to reveal the contribution of genetic and environmental factors to the development of complex diseases. People with type 1 diabetes tend to have lower levels of phospholipids at birth, as well as increased triglycerides and decreased methionine levels. Certain signatures in the microbiome are also characteristic of type 1 diabetes. On the type 2 diabetes front, the characteristic metabolomic factors include branched chain amino acids, more acyl-carnitines (known to cause greater insulin resistance), tyrosine alterations, and an excess of short chain fatty acids. People with type 2 diabetes also have low amounts of butyrate-producing bacteria in their microbiomes. Clearly this research remains very early-stage, but metabolomics has great potential in eventually helping us parse the genetic and environmental risk factors for type 1 and type 2 diabetes, ultimately informingprevention and treatment strategies.
Symposium: If You Build It, They Will Come – But Will They Stay? Recruitment and Retention in Diabetes Trials
Leveraging Technology in Lifestyle Intervention
Sherry Pagoto, PhD (University of Massachusetts Medical Center, Worcester, MA)
Dr. Sherry Pagoto presented a successful strategy of using technology to maximize reach, retention, and adherence in clinical trials. Through the use of social media platforms like Twitter and Facebook, the Habits app was used to engage individuals online in a study that tracked, monitored, and incentivized people to exercise, eat, and sleep in healthier ways. Online engagement saw no drop-off during the duration of the study. Participants were divided into users and super-users, and would post updates regarding their daily exercise routine, caloric intake, and sleep hours. All study participants benefitted from the exchange that occurred in these private social media groups, but the super-users experienced significantly more weight loss and better sleeping patterns than the users. Dr. Pagoto suggested that in a world where technology is rapidly expanding and evolving, investigators should use it to their advantage and develop studies through this engaging platform.
Financial Incentives for Patient Engagement
Robert Jeffery, PhD (University of Minnesota, Minneapolis, MN)
Drawing from a wide variety of studies targeting weight loss, smoking cessation, survey completion, and substance abuse recovery, Dr. Robert Jeffrey analyzed the effectiveness of different financial strategies to encourage positive health behaviors. Financial incentives were shown to be beneficial in the short term, with monetary amount, frequency, pattern, and social context all contributing to outcome. Dr. Jeffery commented that effective incentives for long-term maintenance of behavior warrant further study, since current data indicates that the influence of financial incentives wanes over time.
- Financial incentives generally have more substantial effects on patient health behaviors when they are larger (in monetary amount) and more frequent. Dr. Jeffery established a dose-dependent relationship between incentive size and magnitude of weight loss, where people on average are able to lose more weight if their monetary prize is of higher value. Payment schedule can also invoke changes in overall weight loss. In one study, participants lost more weight if they received award money irregularly vs. in a constant payment schedule.
- Specific target outcomes are better than those that target intermediate behaviors. Direct rewards for weight loss result in greater decreases in body weight vs. incentive plans that award participants for behaviors that may lead to weight loss, such as attending nutrition classes or meeting daily calories goals. Dr. Jeffrey showed that offering a $50 lottery for attending exercise classes increased participation (61% attendance with incentive vs. 52% attendance without incentive), but there was no significant difference in weight loss between the groups.
- Social group dynamics can be leveraged. Structuring rewards based on the mean weight loss of a group results in greater weight loss for each member of the group vs. incentive structures based on individual weight loss alone.
- Financial incentives are more powerful than material incentives. Responses to rewards such as coffee mugs, cookbooks, and t-shirts are weaker than those to pure financial gain, confirming the power of money.
Questions and Answers
Q: I have one observation and a question. We did a review on financial incentives a few years ago, which supported that financial incentives are most effective for specific periods of time when individuals care about a behavior – for example, smoking during pregnancy. You can invoke change during these periods, but it is very difficult once they end. I was also struck that in many of the studies you discussed, the incentives worked for initial weight loss but not for maintenance. What do you think is happening here?
A: Habituation. If you are paying people to change their behavior, at first it is fun, but then it gets boring. That’s when you lose people.
Q: I’m interested in the finding that social incentives for weight loss were more effective. What do you make of this? Are there possible cultural differences?
A: I’m not sure if there are cultural differences. I did think it was a fascinating finding. It seemed that this incentive did not improve the performance of those at the head of the class, but was most effective for those who were struggling because of the fear of bringing the performance of the group down. It also highlights the question of whether rewards are more effective for those of low socioeconomic standing. Most of our studies were done on people with relatively high socioeconomic means, but my guess would be that the effect could be greater for people who really need the money.
Recruiting and Retaining Rural, Minority, and Underserved Populations in Behavior Change Intervention
Doyle Cummings, PharmD (East Carolina University, Greenville, NC)
Given that the African American community is underserved and underrepresented in clinical research, Dr. Doyle Cummings presented a compelling set of strategies to enhance inclusion of this demographic in clinical trials. He captured the urgent need for this inclusion, remarking that the areas in the US with the highest rates of diabetes prevalence are also those with the highest proportion of African Americans. Dr. Cummings established that rural African American communities face the most challenges in diabetes management, pointing to higher A1cs, higher rates of comorbidities, and greater self-reported stress and depression symptoms vs. Caucasian patients. He then showed a dearth of ClinicalTrials.gov search results for “rural,” “African Americans,” and “diabetes.” Detailing the long history of legalized discrimination and poor treatment of this demographic group in the medical sector specifically, Dr. Cummings asserted that many of the issues surrounding the recruitment and retention of rural African Americans boil down to a mistrust of the medical community (he cited examples such as the Tuskeegee Experiment). He argued that the medical/research community should take a more direct approach to regaining this trust by building teams with integrity and character, spending time in the target community to better understand how they perceive diabetes, and engaging with the target community. He warned against simply creating committees and suggested using more direct communication strategies to understand the perspective of the community. As an example, Dr. Cummings explained that his team hired six members of the rural African American community in North Carolina, and using their suggestions, switched to recruiting for clinical trials in churches, resulting in 100% recruitment and 82% retention. His team made a concerted effort to understand the daily difficulties of patients in this particular population and designed “a better study” that brought research components to the community and to primary care offices. Dr. Cummings urged diabetes researchers to look to other disease areas, explaining that cancer drug trials have found that there are higher retention and completion rates when researchers employ patient navigators.
Maximizing Recruitment and Retention in Pediatric Randomized Control Trials (RCTs)
Randi Streisand, PhD (Children’s National Medical Center, Washington, DC)
Given that 45% of pediatric RCTs do not meet recruitment goals, Dr. Randi Streissand suggests that the most important way to increase enrollment in such trials is to engage the young participants themselves. Retention is also an issue with these trials, as only 70-80% of type 1 diabetes youth trial participants come back for follow-up. When investigators design trials, Dr. Streisand suggests using informed consent, managing expectations of parents, and increasing amounts for incentives. She advised that principal investigators keep in mind travel distance, cultural relevance, out of pocket costs, and children’s indifference with regards to participation and follow up in RCTs. According to Dr. Streisand, investigators should also consider having an Advisory Board to receive feedback from current and past trial participants periodically and use their suggestions to modify and build new trials. With all these suggested changes, randomized control trials may be met with more success.
Symposium: Cognitive Decline – Recognizing and Adapting Diabetes Care Strategies
Adapting Diabetes Self-Management Efforts to Maximize Success
Deborah Hinnen (University of Colorado, Colorado Springs, CO)
In this practical talk on adapting diabetes care strategies for patients undergoing cognitive decline, Ms. Deborah Hinnen emphasized the importance of early, careful, and continual cognitive assessments for aging patients. She pointed out that diabetes places extreme financial and cognitive demands on every patient, and the difficulty of fulfilling those demands only increases as a patient ages, both mentally and physically. Cognitive decline is insidious and often masked by the patient for many reasons, but a HCP needs to assess for memory loss and the maintenance of diabetes-related skills to ensure the safety of the patient. That assessment should make it easy for the patient to bring up any trouble they’ve been having, and it should occur early and often—early detection is essential to maintaining quality of life and of treatment regimen. The conversation about potentially receiving daily living assistance in the future should also begin early, and it should involve and engage the patient as much as possible. There are a variety of personal and technology-based resources available to aging patients, and they should be implemented to promote safety and independence.
- Ms. Hinnen reviewed all the factors that make diabetes challenging, from financial constraints to cognitive demands. She used a case study to illustrate the practical barriers to optimizing a diabetes treatment plan. She recalls discussing a variety of medications with lower hypoglycemia risks with a patient, but none of these (GLP-1 agonist, SGLT-2 inhibitors, and basal insulin/GLP-1 agonist coformulations) would qualify under the patient’s insurance, and all insulins available on this patient’s plan would cost more than $100 out of pocket. As a result this patient didn’t take insulin, and was afraid to each lunch because he feared high BG readings. Against this backdrop, Ms. Hinnen underscored that managing diabetes can be overwhelming: on a daily basis, patients have to plan and follow meal plans, monitor glucose, follow medicine regimens, engage in physical activity, recognize and treat highs and lows, engage in daily foot care, manage stress, and handle a number of doctor and lab appointments.
- Cognitive assessment is now required as part of Medicare’s annual wellness visit algorithm, but more work needs to be done in proactive evaluation. The Behavioral Risk Factor Surveillance System includes questions such as “During the past 12 months have you experienced confusion or memory loss that is happening more often or is getting worse?” However, Ms. Hinnen argued that the most important thing HCPs can ask patients is, “During the past 7 days, did you need help from others to take care of things such as laundry, housekeeping, bathing, shopping, using the telephone, food prep, transportation, or taking your own medications?” This question targets the cognitive functions and physical coordination needed for taking care of diabetes, and is easy to add to any assessment. Additionally, it provides an opportunity for patients to bring up any problems they might be having. Then, they can be referred for more extensive evaluation by geriatricians, geriatric psychiatrists, or neurologists.
- Early detection of cognitive decline is crucial to maintaining quality of life and treatment; equally important is beginning the conversation about assistance early. Early detection may help maintain independence, improve quality of care, lessen caregiver stress and depression, and provide opportunity to plan for the future while affected individuals can still participate. The CARES program of Colorado Springs brings together the fire department and two hospitals: as 911 calls from a residence increase, paramedics proactively call on people to ask them to sign up for the program. A HIPPA waiver allows officials to contact PCPs, and the primary diagnoses in the program are diabetes and CV problems. Motivational interviewing is used to help patients identify their own issues, and a navigation team bridges them with formal services. Additionally, beginning the conversation surrounding cognitive decline early on provides the opportunity to plan for the future while the affected individual can still participate. It should be explained that cognitive disease progresses and put into common terms, such as “dementia” if appropriate. Patients should be asked what services can help them at the moment, if they have thought about how their lives will look in the near future, and how they can envision receiving assistance.
- Support systems and strategies can be personal or technology-based, and there are different strategies caregivers and HCPs can utilize to maximize the safety of a patients. Personal support can come from family, friends, and outside caregivers, and the level of involvement should be determined with the patient if possible. Often, it is helpful to escalate the time and extent of support to allow trust and comfort between caregiver and patient to build; eventually, many patients will move into skilled nursing facilities. Relevant assistive devices include CGMs with sharing capabilities, GPS tracking and emergency alert devices, and insulin pens with time and dose memory—there are even outlet devices to help make sure that appliances like stoves get turned off. HCPs should also verify knowledge and basic skills with their patients; rather than just asking if a patient is having trouble, they should be asked to mimic injections or other medication administration, explain what types of food they should be eating, and show how they check their BG and explain what their goals are.
Symposium: Personalized Nutrition by Prediction of Glycemic Responses
Personalized Nutrition by Prediction of Glycemic Responses
Hagit Shapiro, PhD (Weizmann Institute, Rehovot, Israel)
Summarizing some of her research, Dr. Hagit Shapiro explained that in studies done with standard meals of varying types – bread, bread with butter, or glucose – patients showed varied responses in postprandial glucose. She attributed these varying responses to the microbiome, explaining that different microbiota phyla show different responses to different diets. No other independent variable corresponded to the differing responses. This insight led Dr. Shapiro to design a learning machine that would predict postprandial glucose response based on the microbiome. While the correlation between increased carbohydrate consumption and postprandial glucose response is only r=0.38, this learning machine showed a correlation of r=0.68 between predicted response and actual postprandial glucose response. Another study using a further refined version of the learning machine resulted in a correlation of r=0.70. Dr. Shapiro advocated that this learning machine could help patients/providers develop a personalized diet plan that optimizes outcomes. She explained her group’s efforts to use the microbiome to address failure to maintain weight loss: Microbiome changes in previously obese mice that lose weight show an intermediate microbiome composition compared to the composition of obese or lean mice. Mice that cycle back to obesity again show no change in microbiome composition and appear similar to obese mice in terms of microbiome composition. Dr. Shapiro shared that her learning machine was used to predict obesity-based microbiome composition, with a resulting correlation of r=0.72 between predicted and measured obesity levels. She concluded by proposing that microbiota metabolites – particularly flavonoids – could be used to alter the microbiome and ameliorate obesity relapse. We’re intrigued by the learning machine and its potential to personalize diet/lifestyle interventions for type 2 diabetes and obesity. The microbiome is certainly a buzzword these days, and we’re excited to note so much passion for microbiome-based approaches to diabetes and obesity – that said, our enthusiasm is tempered somewhat by the fact that all this research remains very early-stage and has yet to yield a new, concrete therapeutic option. But, this is an area of research that we will continue to watch closely, with high hopes down the line near and far.
Symposium: Patient-Reported Outcomes (PROs) – Using Clinic-Based Screening and Intervention to Inform Diabetes Care
To Screen or Not to Screen – Is That the Question?
Jeffrey Gonzalez, PhD (Yeshiva University, New York City, NY)
Dr. Jeffrey Gonzalez made a case for not routinely screening patients with diabetes for depression, arguing that screening everyone has not been proven to yield better results to treatment, creates a high number of false positive results, taxes the resources of mental health providers who are already stretched thin, and ultimately distracts from addressing the patients more pressing issues. Dr. Gonzalez began by noting that the US is one of the few countries to recommend screening patients regularly for depression, pointing out that Canada and many western European countries do not do so. He then traced the causes of the high number of false positives when patients with diabetes are screened for depression, observing that the standard Patient Health Questionaire-9 (PHQ-9), which is used to screen patients for major depressive disorder (MDD), is not able to distinguish between localized distress and MDD. The standard response for a healthcare provider with patients whose answers to this questionnaire indicate they are at risk for MDD is to refer them to a mental-health resource for initial screening and diagnosis, which Dr. Gonzalez believes risks placing an undo strain on mental-health workers. Instead, he recommends screening on an as-needed basis, focusing on those who are already diagnosed with MDD and other mental-health issues, and advocated health care providers talk to their patients about what’s going on in their lives to help inform their decisions to screen or not. We value this practical opinion and continue to hope for more resources in mental healthcare, for people with diabetes and in general. Specifically, there is a pressing need for improved diagnostic methods that avoid false positives, and a system which has adequate resources and capacity to provide support for those in need of help.
- Dr. Gonzalez argued that standardized questionnaires yield a high number of false positives for MDD. He rapidly worked through a number of studies showing the number of patients whose answers to two common depression screening instruments, the PCHQ-9 and CES-D, fell in the depressive range, but in general only around 30% of those in this range were found to have MDD when diagnosed again in a clinical setting. This translates to a troubling average false positive of 70% across studies.
- He also argued that semantics matter when discussing screening patients: stating that questionnaires that focus on diagnosing MDD risk mislabeling what would be better identified as Diabetes Distress. In particular, somatic symptoms such as trouble sleeping and loss of appetite are all listed on these questionnaires, but are also highly likely to be associated with poor adherence to diabetes treatment.
Questions and Answers
Q: In one of your other talks it sounded like you recommend screening. Can you clarify?
A: I said consider screening. I think if you have a system in place and a psychologist integrated with the staff/resources available, in other words the resources for it are in-house, I think it is reasonable to screen. My fear is that how this is being rolled out is give the PHQ-9 to everyone and then subsequently we over-diagnose and over-treat.
Adult Psychosocial Screening and Intervention – What Providers Need to Know
Paul Ciechanowski, MD (University of Washington, Seattle, WA)
Dr. Paul Ciechanowski emphasized the positive impact on health outcomes associated with integrating screening for psychosocial measures during health visits. Psychosocial screening can help identify which of two styles of human interaction a patient prefers – interactive style and independent style. Different behavioral styles may affect outcomes for people living with diabetes. Dr. Ciechanowski explained that both type 1 and type 2 diabetes patients who belonged to the independent style group often had higher A1c levels. Independent style individuals also missed more appointments, had less satisfaction with care, less treatment adherence, and a 33% increase in mortality in 5 years. As a result, there is a great need to understand what interventions might work best for individuals by understanding individual behavioral styles. Dr. Ciechanowski concluded that integrating an understanding of psychosocial measures into diabetes care will help to foster patient-provider connection and improve medication adherence and outcomes.
- Dr. Ciechanowski explained the difference between interactive style and independent style. He described interactive individuals as those who are comfortable with getting emotionally close to others, find it easy to depend on other individuals, and enjoy emotional intimacy. On the contrary, independent individuals are uncomfortable sharing their emotions, do not easily depend on others, and worry that they will be hurt if they get too close to another individual.
- Dr. Ciechanowski identified several behavioral tests that may be helpful for better understanding patients and identifying which behavioral style they may best align with. He mentioned the Diabetes Distress Scale, the Problem Areas is Diabetes (PAID) test, PHQ-9, which measures depression, and the Summary of Diabetes Self-care Activities (SDSCA) Measure. Incorporating these behavioral evaluations into healthcare systems may allow providers to better understand and help their patients.
Symposium: Overtreatment in Diabetes Management
Supporting Personalized Patient-Centered Care Through Shared Decision-Making
Elbert Huang, MD (University of Chicago, IL)
Dr. Elbert Huang discussed a number of reasons we, as a community, have failed to personalize diabetes care in practice despite the recent increase in discourse on this topic. He touched on a number of explanations from psychological phenomena such as ego bias (“I’m doing well but others suck”) and status quo bias (“it’s difficult changing anything when you’ve been doing it a certain way”) to the perpetuation of old recommendations (e.g., it takes a long time to re-teach an entire generation of providers) to the simple fact that clinicians are tremendously busy and that weighing the risks and benefits of treatments is cognitively challenging and time consuming. With that in mind, he concluded that digital tools are going to be key in facilitating a true personalized decision-making revolution, noting that one big challenge is developing a system that is true to the latest evidence-based reasoning and that takes into account individual patient preferences. He drew a line as well between “shared decision-making” and “decision support” software – noting that the later actually nudges patients and providers in a certain direction – and encouraged attendees (both manufacturers and clinicians) to consider this difference when designing and using such tools.
Symposium: The Neglected Delta Cell
The Difference Delta Cells Make in Glucose Control
Mark Huising, PhD (University of California, Davis, CA)
Dr. Mark Huising presented a compilation of several studies on the pancreatic delta cell, demonstrating that it plays a vital role in human islets by maintaining the homeostatic set-point for glucose. Dr. Huising began by placing the delta cell in context with human islet function: it is the third most common cell type in the islet after the better-known glucose-secreting alpha cells and insulin-secreting beta cells, and is responsible for the release of somatostatin, which maintains glucose homeostasis by coordinating glucagon and insulin release from the alpha and beta cells. The release of somatostatin from delta cells is triggered by urocortin3 (Unc3) from the beta cells and ghrelin from the GI tract. Dr. Huising believes that further study of delta cell function will help pre-empt what he called “vicious cycle of hyperinsulinamia and hyperglucagonemia,” for people with diabetes, noting that even those with good glycemic control will experience far more variation in glucose levels than those with fully functioning islets.
Questions and Answers
Q: Can you rescue SST secretion with ghrelin?
A: We haven’t done it, I would guess you can.
Q: Do you think Unc3 is a necessary part of insulin secretion or just has a role in feedback loop?
A: It is not required for beta cells to secrete insulin, but does regulate the levels of insulin.
Symposium: The Stigma of Diabetes – An Underappreciated Reality
Susan Guzman, PhD (Behavioral Diabetes Institute, San Diego, CA); Lindsay Jaacks, PhD (Harvard University, Boston, MA)
ADA 2017 kicked off with a morning symposium on a critical but under-recognized and under-researched topic: the stigma of diabetes. Dr. Susan Guzman, a clinical psychologist at the Behavioral Diabetes Institute (founded by the great Dr. William Polonsky and the only nonprofit dedicated to psychological issues of diabetes) led with a discussion of the feelings of guilt, shame, blame, embarrassment, isolation that too often accompany living with diabetes. Drawing largely on data from diabetes market research firm dQ&A (outlined in detail at AADE 2016 by our very own Mr. Adam Brown), Dr. Guzman described how these negative emotions are exacerbated in people with more intense therapeutic regimens, higher BMI, higher A1c, and poorer self-reported “control” – in other words, those most in need of help are also the most negatively impacted by diabetes stigma. She powerfully illustrated the judgment and misunderstanding surrounding diabetes with a timely allusion to a statement made a month ago by Budget Director Mr. Mick Mulvaney, who, when asked about how healthcare policy should handle pre-existing conditions, remarked that the US government shouldn’t have to “take care of the person who sits at home, eats poorly and gets diabetes” in future iterations of healthcare reform. Against this troubling backdrop, Dr. Guzman reminded the audience that diabetes is not a choice, and managing this disease is very hard work, underscoring the crucial role healthcare professionals can play in replacing society’s negative messaging surrounding diabetes with facts and empathy. We’re so glad that Dr. Guzman is drawing attention to this very important topic. Further, we were impressed by the primetime positioning for psychosocial issues related to diabetes care at ADA 2017.
- Harvard University’s Dr. Lindsay Jaacks continued the discussion, delving into the arguably even more severe diabetes stigma that exists in low- and middle-income countries (where the majority of people with diabetes live). Her research on the experiences of living with diabetes in China and India reveals a widespread phenomenon of people hiding their diabetes from friends, family, and co-workers and uncovered several key structural issues that people with diabetes face in emerging countries, such as difficulty finding a spouse due to extreme stigma, and a lack of institutional policies to prevent the discrimination of people with diabetes.
- Though diabetes stigma is experienced differently across cultures, Dr. Jaacks argued for a universal underlying framework: stigma leads to mutually reinforcing cycle of distress/depression and suboptimal self-management practices, ultimately giving way to poor glycemic control and elevated risk of diabetes complications. Thus, anywhere in the world, educating the general public about diabetes could not only reduce the stigma that people with diabetes experience, but also potentially improve self-management and health outcomes.
Special Lectures and Addresses: President, Medicine & Science Address and Banting Medal for Scientific Achievement
Banting Medal for Scientific Achievement – The New Biology of Diabetes
Domenico Accili, MD (Columbia University, New York, NY)
In this year’s inspiring Banting Medal for Scientific Achievement lecture, Columbia’s Dr. Domenico Accili presented his vision of a revamped toolkit for diabetes care in 2021, 100 years after the discovery of insulin: Prevention of beta cell de-differentiation, a gut-targeted Foxo1 inhibitor to coax gut cells into producing insulin in a glucose-dependent manner, and selective insulin sensitizers. These sound like ambitious goals, but Dr. Accili conveyed confidence-inspiring narratives around each. The meat of his talk focused on dispelling the perception that beta cell failure is a consequence of beta cell death. His data seem to suggest that beta cell dedifferentiation, not necessarily death, is actually to blame. In the islets of individuals with diabetes, beta cells are still alive, but they lose their expression of insulin and other beta cell-typical hormones and come to resemble progenitors – in fact, the number of hormone-negative cells in human islets can be as high as 30%, and the process of dedifferentiation is consistent with the clinical features of type 2 diabetes. Eventually, some of these even convert to glucagon-producing alpha-like cells. Dr. Accili sees a big opportunity here: If beta cells are not dead, but just quiescent as dedifferentiated of converted cells, then there’s a chance to restore beta cell health even after the onset of hyperglycemia. For type 1 diabetes, Dr. Accili’s lab has set sights on coaxing gut cells into producing insulin in a glucose-dependent fashion. Early studies found that knocking out FOX1 yields insulin positive cells in the gut, which exhibit glucose-dependent insulin secretion ex vivo. The strategy of converting intestinal cells into insulin-producing cells may be better suited to treat type 1 diabetes than stem cell-derived beta cells because the gut has “immune privilege” (the cells are less likely to be targeted as invaders), endocrine cells have a short half life in the gut, and so escape destruction, and gut cells continually regenerate, ensuring a renewable reservoir. In Dr. Accili’s opinion, “there’s no reason why this should not work.” Lastly, for type 2 diabetes, Dr. Accili explained that it is possible to modulate critical nodes of insulin signaling to dial up/down individual bio-responses, enabling selective reversal of insulin resistance – any therapeutic agent in this vein could reduce the burden on overwhelmed beta cells and preserve glycemia for extended periods of time. With a portfolio this lengthy and deep, we can’t think of anyone more deserving of this award than Dr. Accili – our only hope is that he sticks with it and delivers 2021: A Diabetes Odyssey.
Special Lectures and Addresses: President, Health Care & Education Address and Outstanding Educator in Diabetes Award Lecture
A Toast to Our History
Davida Kruger, MSN (Henry Ford Medical Group, Detroit, MI)
Upon receiving the Outstanding Educator in Diabetes Award, a humbled and passionate Ms. Davida Kruger shared her work in diabetes over the past 35 years, as she provided insights on her role in the DCCT, as a nurse practitioner in diabetes, and as an ADA volunteer. In an emotional opening, Ms. Kruger shared her personal reasons for working in diabetes, as she touched on the diabetes diagnoses and complications she watched her mother and other family members experience. Moving into the beginnings of her career, she discussed her role in the DCCT, emphasizing the development and evolution of the role of trial coordinators during this time and the emergence of different team member roles throughout the process. Notably, Ms. Kruger continued by stressing the increasingly important role of the nurse practitioner, as diabetes prevalence increases and the clinical endocrinologist workforce declines. Along these lines, she presented data showing that nurse practitioners make equally accurate diagnoses as physicians and are also more likely than physicians to provide health education and promotion, adapt medical regimens to the patient’s preferences, and listen more to the patient. Lastly, Ms. Kruger touched on her work as an ADA volunteer, specifically pointing to the importance of fundraising for the Association’s research foundation. In conclusion, Ms. Kruger expressed appreciation for her family, mentors, and colleagues, as she closed by stating that the field “must remain open to all team members” and keep the patient at the “head of the team.” Ms. Kruger left the podium with a standing ovation and our team joins the diabetes world in our deepest gratitude and admiration for Ms. Kruger’s incredible leadership and service to the field.
The Pillars of Prevention – Discover, Advocate, and Educate
Brenda Montgomery, RN (AstraZeneca, Bellevue, WA)
Ms. Brenda Montgomery, ADA President of Health Care & Education, discussed the ADA’s efforts in the fight against diabetes with a particular eye toward prevention. She organized her remarks in accordance with the ADA’s three strategic imperatives: (i) Drive Discovery, through research, partnership, and innovation; (ii) Raise Voice, to intensify the urgency around the diabetes epidemic and mobilize action; and (iii) Support People, to continually develop new and effective resources for people affected by diabetes. On the prevention front, the ADA has driven discovery through its support of the original DPP trial and its subsequent iterations in real world settings and in various international locations. In terms of raising voice, Ms. Montgomery pointed out that the ADA has tirelessly advocated for the passage of the Diabetes Prevention Act, legistlation to establish a national diabetes prevention at the CDC, and has worked with the YMCA to advocate for the establishment and funding of the NDPP. Finally, in supporting people the ADA has worked to broaden access to diabetes prevention services through Medicare coverage and has facilitated the national scaling of prevention. All in all, Ms. Montgomery surmised the ADA’s work in the prevention space as a story of “small steps leading to big rewards.” To illustrate this, she pointed out the immense progress the field has made since 1993 when the DPP was first initiated: indeed, diabetes prevention is now a field all its own.
Special Lectures and Addresses: Kelly West Award for Outstanding Achievement in Epidemiology (Sponsored by Merck)
Diabetes in Youth – Looking Backwards to Inform the Future
Dana Dabelea, MD (University of Colorado, Denver, CO)
Dr. Dana Dabelea underscored the need to look backwards to see the developmental origins of diabetes before making decisions on how to treat it (and on a population level, how to prevent it). These developmental origins include stress, nutrition, smoking, pollution, social environment, maternal condition, and toxins. Dr. Dabelea highlighted gestational diabetes, reporting that exposure to diabetes in utero is the strongest risk factor for type 2 diabetes in youth. She discussed the Healthy Start Study’s findings that increased gestational weight gain and maternal high-fat diet are associated with increased neonatal adiposity. This same study also demonstrated that higher levels of late-pregnancy total energy expenditure are associated with decreased neonatal adiposity, and that neonatal adiposity but not birth weight significantly predicts obesity at age three. This and other studies highlight the need to focus on diabetes prevention earlier in life. As Dr. Dabelea put it, the vicious cycle of diabetes and obesity needs to be broken in several places.
Special Lectures and Addresses: National Scientific & Health Care Achievement Awards Presentation and Outstanding Scientific Achievement Award Lecture
Energy Sensing and Metabolism – Implications for Treating Diabetes
Gregory Steinberg, MD (McMaster University, Ontario, Canada)
In a fascinating summary of his award-winning basic science research, Dr. Gregory Steinberg shared how his work on energy sensing and metabolic regulation could create exciting, novel therapies for diabetes treatment. Steinberg centered his talk around AMPK, a ubiquitous protein that is activated by metformin, and explained that this protein kinase is like a fuel gauge that tells the cell when to fill up with energy. He continued by explaining that increased AMPK levels may increase insulin sensitivity and tolerance and reduce lipid sensitivity. Simultaneously metformin also increases levels of GDF15, a protein that works in similar ways to AMPK and is another cellular ‘fuel gauge.’ Steinberg explained that his most recent work has been in finding pharmacological agents that could activate these fuel gauges. He further suggested that AMPK can activate transformation of white adipose tissue into brown adipose tissue (BAT), based on evidence in mice lacking AMPK demonstrating that they are not able to regulate their own body temperature and develop insulin resistance despite eating the same diet as wild type mice. While there is no established method for restoring BAT, Steinberg explained that norepinephrine can activate transformation of BAT and also can inhibit serotonin production through a series of intermediary, rate-limiting enzymes. He noted that reduction of peripheral serotonin protects against obesity in mice. Dr. Steinberg concluded his talk by circling back to his research’s relevancy to patients with type 2 diabetes, arguing that further examination of how to manipulate these cellular fuel gauges could lead to important, groundbreaking therapies in the treatment of type 2 diabetes.
Professional Interest Group Session: Joint Consensus Statement on the Use of Language in Diabetes – Why Language Matters
Jane Dickinson, PhD (Teachers College, Columbia University, New York, NY)
Dr. Dickinson gave an intensely personal talk on the power of language and the role that it plays in diabetes. She opened with a story about an adolescent girl at diabetes camp with blood glucose above 200 mg/dl who hid in her cabin because she was too ashamed to tell anyone. These types of responses and stigma are a product of negative messaging and language around diabetes care. Dr. Dickinson also spoke about her experiences in a clinic where patients were referred to by their disease (i.e. diabetics), which puts the disease before the person in the eyes of the healthcare provider. One powerful way she suggested to combat this type of thinking was asking patients the question “What do you want me to know about you?” to humanize them. Dr. Dickinson addressed the widespread use of the word “control” in diabetes. One of the patients she worked with put his head in his arms and sobbed when he found out his cannula had not delivered his insulin, saying “I work so hard on this and I never get it right.” In the past, he had received a lot of criticism for being “poorly controlled” and it made him hesitant to seek education and support. Another young man she worked with as an inpatient had PTS and had blood glucose numbers in the 400-500 mg/dl range for years. He was proud that he had brought his numbers down to 200 mg/dl but then still received a lot of derision from healthcare providers and was extremely discouraged from continuing. These stories so deeply communicate how the language and messages we send to patients are important from the very first encounter because we might not get another chance with that person.
- Dr. Dickinson dedicated a lot of attention to the word “non-compliant,” which unfortunately still persists among healthcare providers. “Non-adherent,” she argued, is just a cousin of “non-compliant” that implies people are not doing what providers want them to do. Instead, Dr. Dickinson urged providers to focus on what people are doing rather than judging them and understand that words can be helpful or hurtful. As an example, a provider once asked Dr. Dickinson, “How long have you suffered from diabetes?” She answered, “I’ve had diabetes for 20 years but I don’t suffer.” Providers have an opportunity to examine our language and make changes so that we can help people live well with diabetes without stigma and misunderstanding.
Support from the Research
Susan Guzman, PhD (Behavioral Diabetes Institute, San Diego, CA)
Dr. Susan Guzman shared a more academic perspective of how language conveys and perpetuates stigma. She shared her experience as a clinical post-doc, watching providers talking about their patients but not talking to them. There are a lot of reasons that people struggle with diabetes, and calling the behavior noncompliant does not make sense for why people decide to act certain ways. Providers can go into rooms with expectations and not listen to their patients. Dr. Guzman discussed research that encourages health care professionals to consider howlanguage influences expectationsthat can affect how people think about themselves andtheir experience with diabetes. Expectancy theory can apply to diabetes as well; for instance, when patients who are labeled as uncontrolled are less likely to be prescribed insulin. Dr. Guzman highlighted a recent study by Dr. Bill Polonsky, which demonstrated that positive messages improved the quality of communication between patients and providers and had a positive impact on health behaviors. Importantly, language conveys meaning that can determine expectations that lead to bias, and messages that convey stigma can lead to distress and disengagement. Healthcare providers have an important role in defining this experience by communicating supportive and collaborative messages.
- In a study of words that negatively affect patients, Dr. Dickinson found that six themes emerged: (i) Judgment (noncompliant, uncontrolled, don’t care, failure); (ii) Fear/Anxiety (complications, blindness, death, DKA); (iii) Labels/Assumptions (diabetic, all people with diabetes are fat, suffering); (iv) Oversimplifications/Directives (lose weight, you should, you’ll get used to it, at least it’s not…); (v) Misunderstanding/Misinformation/Disconnection (cure, reverse, bad kind, you’re fine); and (vi) Body Language and Tone (no eye contact, accusatory tone). If these words were not used, patients said that they would feel respected and listened to, and reassured that their providers care.
- The way we talk about diabetes also reflects diabetes stigma by reflecting the idea that people with diabetes have done something wrong or that people with diabetes are perceived as having a character flaw or a failure of personal responsibility, being a burden on the healthcare system, or being weak, fat, lazy/slothful, overeaters, poor, bad, or not intelligent. Dr. Guzman pointed out that this can lead to feelings of guilt, shame, blame, fear, and embarrassment and negative health outcomes from disengagement, isolation, and depression.
Recommendations for Practice
Melinda Maryniuk (Joslin Diabetes Center, Boston, MA)
Ms. Melinda Maryniuk presented recommendations from an upcoming formal paper from the AADE and ADA on the use of language in diabetes care and education. The paper’s guiding principles are that (i) diabetes is complex; (ii) stigma has been historically attached to diabetes diagnosis; (iii) the healthcare team can serve people with diabetes more effectively through a respectful, inclusive, and person-centered approach; and (iv) that better language can enhance motivation and health. She emphasized that the paper is not about banning words, but more about becoming aware of and changing words. Some examples include using “people living with diabetes” instead of “diabetics,” using “check” or “monitor” blood sugar instead of “test,” “managing” diabetes instead of “controlling” it, emphasizing “safe” or “target” goals instead of labeling patients or their diabetes management as “good,” “bad,” or “poor,” and using descriptions such as “a patient who takes medicine about half of the time” instead of a label like “nonadherent” or ‘noncompliant.” Overall, the paper is a call to action to have more open and honest discussions between patients and providers. We eagerly await the paper’s full publication and are optimistic that it will be especially influential in making the next generation of health care professionals more sensitive to the use of helpful language and effective communication in diabetes.
-- by Ann Carracher, Abigail Dove, John Erdman, Helen Gao, Varun Iyengar, Brian Levine, Nancy Liu, Marissa Lynn, Payal Marathe, Emily Regier, Maeve Serino, Pearl Subramanian, Lisa Vance, Emily Yang, Yrenly Yuan, and Kelly Close