December 2-4, 2016; Atlanta, GA; Full Report – Draft

Executive Highlights

Our team spent the first weekend of December in Atlanta, GA for the ninth World Congress on the Prevention of Diabetes and its Complications (WCPD 2016). Wow was this a great meeting! Speakers from around the world shared their perspectives on primary, secondary, and tertiary prevention, discussing  type 2 diabetes, prediabetes, and obesity in intimate, interactive sessions – we even attended a session on type 1 diabetes prevention. Below we report all of our learnings from this incredibly valuable meeting.

Detailed Discussion and Commentary

Keynote Lectures

Pharmaceutical Interventions for Diabetes Prevention

John Buse, MD (University of North Carolina, Chapel Hill, NC)

Among the many arguments we heard in support of metformin as a prediabetes intervention, Dr. John Buse presented one of the strongest with a compelling economic and evidence-based case for metformin as a population-level prevention strategy. Dr. Buse  reviewed a number of prevention studies – including the ORIGIN trial investigating insulin glargine (Sanofi’s Lantus), the SEQUEL trial investigating phentermine/topiramate extended-release (Vivus’ Qsymia), the SCALE program investigating high-dose liraglutide (Novo Nordisk’s Saxenda), and the EDIT and Diabetes Prevention Program (DPP) trials investigating metformin – ultimately concluding that metformin should be considered as a first line of defense in people with prediabetes. Dr. Buse underscored that “Saxenda is definitely effective” in stimulating weight loss and delaying type 2 diabetes, but turned to economics to show why metformin is the most reasonable approach to prediabetes. It would cost a little over $4 billion to treat the entire US prediabetes population with metformin vs. >$1.2 trillion to treat this group with liraglutide. Meanwhile, we learned in a separate session that intensive lifestyle intervention as provided by the DPP costs ~$100/person/session – treating 86 million Americans with prediabetes would thus run a bill of ~$1.4 trillion. These numbers make it hard to argue against metformin as a population-level solution for type 2 diabetes prevention (although on an individual basis, other pharmacotherapies and particularly liraglutide could confer a substantial benefit to those who can afford it, plus we imagine that lifestyle intervention could play an important supplementary role to metformin in those who can tolerate it). No therapies are yet FDA-approved for the treatment of prediabetes – as this population at risk for type 2 continues to grow, we hope to see metformin indicated for diabetes prevention sometime soon, though this would likely require advocacy with patient, physician, and professional groups. In fact, this is going on, but there actually doesn’t appear to be much enthusiasm at the FDA from what we hear. Although popular believe has it that there is little incentive for pharmaceutical companies to push for a prediabetes indication for a generic medication, we don’t think that is necessarily true. At any rate, while there certainly is professional enthusiasm, that doesn’t appear to be enough to drive regulatory action.

•  “Right now, there’s a clear case to be made for using metformin in 2016.” Dr. Buse wrapped-up his insightful remarks with a suggestion of future preventative therapies – from insulin-sensitizing agents that slow disease progression to novel treatments that affect islet cell biology – but emphasized that metformin is our best option today for the great majority of people who could benefit from a preventative pharmacotherapy.
• Dr. Buse also outlined key characteristics of individuals who will likely benefit most from preventative metformin – namely younger people who are very overweight, with high blood glucose. In studies of the DPP, metformin was just as effective as intensive lifestyle intervention among participants with BMI >35 kg/m² and those in the highest bracket of fasting blood glucose. In contrast, metformin was minimally effective in the oldest participants enrolled and among those with BMI <30 kg/m². Dr. Buse explained that because metformin is a “very effective glucose-lowering agent,” the magnitude of preventative benefit is greatest in people with higher baseline blood sugar. He also mentioned that metformin works particularly well in women with a history of gestational diabetes, now at increased risk for new-onset type 2.
• Regarding alternative therapies for prediabetes: Despite a reduced incidence of new-onset type 2 diabetes associated with insulin glargine, Dr. Buse explained that the weight gain and hypoglycemia risk introduced by this therapy outweigh the potential preventative effects. While Qsymia was “quite effective” in SEQUEL, “on the order of 80% risk reduction,” he pointed out that the overall incidence of diabetes in the studied population in the trial was moderate to low, which impedes conclusive evidence for a large-scale preventative benefit in the general population. Similarly, the rate of diabetes development in the SCALE study population was ~1% per year, suggesting that, despite liraglutide’s potency as a weight loss agent, the preventative benefit has only been demonstrated in a portion of the population that has a low risk of progression to diabetes anyway.

Prevention of Beta Cell Failure: The Changing Face of Type 1 Diabetes

Paolo Pozzilli, MD (University Campus Bio-Medico, Rome, Italy)

Dr. Paolo Pozzilli provided an update on prevention efforts for type 1 diabetes at the primary and secondary levels. For type 1 diabetes, primary prevention entails intervening when two or more type 1-associated islet autoantibodies are present but glycemic control remains normal (stage 1 type 1 diabetes, under the JDRF/ADA staging system). Trials of this kind, which often involve dietary interventions, have had mixed success. For instance, infants with a family history of type 1 diabetes and autoantibody-confirmed risk had decreased incidence of beta cell autoimmunity after several months of drinking formula free of β-casein (Knip et al., 2010) but no such effect was found for infants restricted to a gluten free diet (Beyerlein et al., 2014). Although we are far from having a consensus on viable primary type 1 diabetes prevention efforts, Dr. Pozzilli underscored that large, long-term studies such as the TEDDY trial are underway and may provide important insights on the environmental determinants of type 1 diabetes for children with high genetic risk. Secondary type 1 diabetes prevention entails intervening when an autoimmune response and dysglycemia is detectable but symptoms have not yet appeared (stage 2). Two studies of note have attempted this – the ENDIT trial using nicotinamide and a Finnish study using nasal insulin (Näntö-Salonen et al., 2008) – though neither demonstrated a protective effect versus placebo. Despite the mixed results for type 1 diabetes prevention efforts thus far, TrialNet has a number of ongoing prevention studies enrolling individuals with stage 1, stage 2, and newly-diagnosed type 1 diabetes – we find these very promising.

• Dr. Pozzilli also discussed the “changing face of type 1 diabetes,” forecasting that tertiary type 1 diabetes prevention may soon become an option for preventing complications and disease progression after symptoms have already become manifest. The main aim of tertiary type 1 diabetes prevention, in Dr. Pozzilli’s view, is not to reverse the disease and stop insulin therapy, but to protect the beta cells from complete destruction. He believes this may be feasible with the use of pharmacotherapies originally developed for type 2 diabetes, such as GLP-1 agonists and SGLT-2 inhibitors. The GLP-1 agonist liraglutide (Novo Nordisk’s Victoza) has been demonstrated to reduce insulin requirements in longstanding type 1 diabetes patients (Kielgast et al. 2011), and exenatide (AZ’s Byetta) administration significantly reduces postprandial blood glucose in people with type 1 diabetes (Sarkar et al. 2014) – that said, Novo Nordisk declined to pursue a type 1 diabetes indication for liraglutide following the phase 3 ADJUNCT ONE and TWO trials that revealed concerning safety signals in terms of hyperglycemia with ketosis and hypoglycemia, coupled with modest A1c reduction efficacy. On the SGLT-2 inhibitor front, EASE-1 trial demonstrated the effectiveness of empagliflozin (Lilly/BI’s Jardiance) to rapidly reduce insulin dose and improve metabolic control in type 1 patients (Pieber et al. 2015).

Prevention Through the Use of the AACE Algorithm and Guidelines

AACE Obesity Guidelines

Timothy Garvey, MD (University of Alabama, Birmingham, AL)

Dr. Timothy Garvey made the powerful argument that effective diabetes prevention must be grounded in meaningful efforts for obesity prevention. One of the original composers of the AACE obesity treatment algorithm, Dr. Garvey overviewed the genetic, biological, and environmental factors that conspire to produce obesity, emphasizing that obesity not a lifestyle choice and its treatment goes far beyond a simple ratio of energy intake and energy expenditure. When obesity is addressed (which is not often the case – as we learned from the ACTION study only 55% of Americans with obesity have received a formal diagnosis, and only 65% perceive obesity as a disease) treatment strategies are typically determined in a BMI-centric framework, whereby an individuals’ BMI determines what type of therapy – lifestyle, medications, and/or surgery – is most appropriate. Dr. Garvey argued for a more complications-centric approach, where instead physicians and patients agree upon a personalized treatment strategy together based on the individual’s unique obesity complications (sleep apnea, cardiovascular disease, diabetes/prediabetes, etc.) and how they impact their daily life. Lifestyle modification is always the cornerstone of this approach, sometimes in combination with pharmacotherapy or surgery according to careful consideration of efficacy, safety, and cost. Dr. Garvey reflected that, as an epidemic that affects two-thirds of our society, obesity endured a long and difficult road to official status as a recognized disease (the AMA only made this designation as of June 2013, thanks to strong encouragement from AACE and ACC), but is finally beginning to be taken seriously. We hope that a complications-centric approach to obesity management can help patients and the public better understand and address the health risks associated with obesity, while also separating these risks from the aesthetic evaluation of body weight – in this way, we hope that obesity stigma can be reduced (we’ve heard heartbreaking stories from patients with obesity at the stigmatization they faced from even the healthcare community from providers who were unable to look past their weight to address underlying health concerns). There is certainly cause for optimism, and we hope this change in perception for obesity foreshadows a similar increasing sense of urgency around prediabetes.

AACE Treatment Algorithms

Alan Garber, MD (Baylor College of Medicine, Houston, TX)

A workshop on the AACE prediabetes and obesity treatment algorithms discussed the multiple meanings of “prevention.” Primary prevention refers to the standard notion of prevention – stopping a disease from occurring. Pursuing this involves interventions that eliminate risk factors: in the context of type 2 diabetes, this means preventing dysglycemia from ever setting in (likely by promoting healthful food and lifestyle choices). Secondary prevention refers to halting the early progression of a disease with interventions that attenuate the onset of complications and worsening of the disease. This translates to preventing prediabetes from progressing into diabetes (again by promoting lifestyle change, perhaps in addition to metformin). Finally, tertiary prevention refers to minimizing the complications of a disease and minimizing further deterioration. This translates to aggressive diabetes management with a combination of lifestyle modification, oral agents, injectable drugs. Minimizing the societal impact of diabetes clearly requires efforts in all three domains of prevention, but a major theme of the meeting was that early primary prevention measures hold perhaps the greatest potential, especially if promoted at a systemic level. Certainly, primary prevention strategies are often the lowest cost and most widely applicable, but also often receive the least funding and attention in the current healthcare paradigm.

Symposium: Diabetic Hypoglycemia - Questions and Controversies

Hypoglycemia Classification

Simon Heller, MD (University of Sheffield, UK)

Dr. Simon Heller of the International Hypoglycemia Study Group made the case for a revised definition of hypoglycemia. He advocated that hypoglycemia needs to be measured in more depth and proposed a third prong in between <70 mg/dl as an “alert value” and <40 mg/dl as a sign of severe impairment requiring external assistance – <54 mg/dl would be added as an indication of clinically-relevant, severe hypoglycemia, creating a more comprehensive schematic of hypoglycemia in clinical trials and diabetes care. The current classification of hypoglycemia “lacks in important areas,” according to Dr. Heller. He pointed out that real-world prevalence of hypoglycemia is five-10x higher than it is in clinical trials, which is especially problematic given that hypoglycemia has a profound effect on a patient’s quality of life. The <70 mg/dl marker doesn’t necessarily need to be measured in clinical trials, since it’s not always relevant to patients and functions more as an alert for people to prevent even lower blood sugar. When glucose falls below 40 mg/dl, patients may already be experiencing severe cognitive impairment, seizure, or coma. Dr. Heller elaborated on evidence for the clinical significance of the <54 mg/dl mark, arguing that this addition would make for a more complete hypoglycemia definition. At this level, children have been shown to have significantly longer reaction time, people’s response and ability to recognize hypoglycemia begins to be impaired (exacerbating their risk for future severe hypoglycemia episodes), and arrhythmias are triggered. In the NICE-SUGAR study, investigators found an association between recurring blood glucose <54 mg/dl and increased mortality. In summarizing this data, Dr. Heller highlighted the “clearly important association between glucose of this level and adverse effects.” He shared that this suggested change to hypoglycemia classification has been accepted by the ADA/EASD as a position statement, and will be published in Diabetes Care and Diabetologia simultaneously in January. We’re glad to see greater discussion and consensus around the definition of severe hypoglycemia. If adopted by the field, this revision could enhance our ability to quantify hypoglycemia in clinical trials and to treat hypoglycemia in real-world clinics.

• That said, there may still be some disagreement regarding the exact blood glucose threshold for severe hypoglycemia – while Dr. Alexander Fleming (formerly of the FDA) forecast a convergence toward a single regulatory definition of severe hypoglycemia with a threshold of 54 mg/dl at WCTD 2016, Dr. Phil Cryer proposed a cut point of 50 mg/dl at Keystone 2016. Overall, we’d like to see greater consensus on this point, particularly from a regulatory standpoint so that new therapies can more concretely demonstrate hypoglycemia benefits – we hope that the ADA/EASD position statement will make strides toward this consensus.

Impaired Awareness of hypoglycemia

Stephanie Amiel, MD (King’s College London, UK)

Approximately 40% of people entering the DAFNE (Dose Adjustment for Normal Eating) structured education program in the UK are hypo unaware, according to the great Dr. Stephanie Amiel (King’s College London, UK). The DAFNE program is able to restore awareness to some. For others, pumps, glucose sensing technology, and other devices help correct for the unawareness. Still, Dr. Amiel commented that we’re left with ~10% of the adult type 1 diabetes population who cannot avoid hypoglycemia or regain their awareness. She discussed three “thinking traps” that perpetuate hypo unawareness for this group: (i) the feeling that low blood sugar won’t happen again; (ii) the compulsion to avoid hyperglycemia at any cost (otherwise “I’ll ruin my diabetes control”); and (iii) the desire “not to make a fuss” or let lows affect one’s life. Dr. Amiel expressed disappointment over these thinking traps, but emphasized that they are not unaddressable – cognitive behavioral therapy could be a particularly powerful tool in addressing these barriers to hypoglycemia avoidance. She reminded the audience that once patients break the habit of repeated lows, or blood glucose <54 mg/dl, their hypo unawareness does dissipate. She also presented pilot data on hypoglycemia awareness restoration training from the DAFNE HART study – unawareness effectively disappeared in 20 patients, and three years later most of these patients remained hypoglycemia-free. A larger, randomized controlled trial of this training method is in the works. Dr. Amiel highlighted the urgent need to confront hypoglycemia in all people with diabetes, even and especially those with stubborn cases of hypo unawareness.

Fear of Hypoglycemia

Linda Gonder-Frederick, MD (University of Virginia, Charlottesville, VA)

Continuing on the theme of the psychology underlying diabetes, Dr. Linda Gonder-Frederick (University of Virginia, Charlottesville, VA) discussed the universal problem of hypoglycemia fear. She shared that the Hypoglycemia Fear Survey, developed at the University of Virginia, has been translated to >60 languages, which goes to show the ubiquity of this problem worldwide. Fear of hypoglycemia stems from numerous factors – Dr. Gonder-Frederick touched upon the impact of hypoglycemia history (even one traumatic episode involving injury can produce significant fear) as well as general anxiety, which predisposes some individuals to hypoglycemia fear more than others. While a small amount of fear can be adaptive – helping people avoid repeat instances of blood glucose <54 mg/dl – she also outlined the adverse effects on quality of life. Hypoglycemia fear has been linked to anxiety, depression, a dampened sense of diabetes self-efficacy, restrictions on normal activities such as travel, and relationship tensions.

Panel Discussion

Simon Heller, MD (University of Sheffield, UK); Stephanie Amiel, MD (King’s College London, UK); Linda Gonder-Frederick, MD (University of Virginia, Charlottesville, VA)

Q: When should we treat hypoglycemia? Should we wait for symptoms, wait till blood sugar <70 mg/dl, or wait till blood sugar <54 mg/dl?

Dr. Heller: If somebody is symptomatic, they should be treated, as long as you confirm that they are in fact hypoglycemic. The alert value of 70 mg/dl is a test, but it really depends on how glucose is trending. Is it going up or going down? Are they about to eat a meal? I don’t think you can establish a hard and fast rule. Patients should be educated to recognize their symptoms and take action, but there’s no guarantee that the same solution will work every time.

Dr. Amiel: I agree with what’s just been said. The identification of <70 mg/dl as an alert to the patient to prevent hypoglycemia is crucial. What we teach our patients with blood glucose monitoring is that they should take action at <70 mg/dl. Patients are more likely to over-treat if they’re away from supportive family and friends, so we also teach people what action to take and help them gain confidence. We also teach that treating hypoglycemia at <70 mg/dl is important, otherwise you may stop feeling symptoms and lose awareness. On the flip side, if you can prevent low blood sugars <54 mg/dl, you can regain your awareness.

Dr. Gonder-Frederick: The only thing I’d add is that behavioral context also needs to be considered. If someone is about to drive a car, maybe treat even >70 mg/dl if there’s a chance that glucose is trending down. We’ve unfortunately seen tragic results from parents with type 1 diabetes having hypoglycemia-related accidents when they’re caring for small infants.

Q: What additional hypoglycemia education would you provide other than sharing signs and symptoms and explaining the <54 mg/dl marker?

Dr. Amiel: Patients are taught to recognize their personal hypoglycemia symptoms and to think about themselves so they can pick up on extra cues of what works for them. Teaching people the consequences of not treating hypoglycemia is very important, but if people aren’t taking swift action, shouting out them louder doesn’t work. Think about the psychological barriers to treating hypoglycemia that Linda and I have alluded to this morning. In the HART program, the most common thing people with impaired awareness do is delay – so, perhaps the most important message is “don’t wait.” Tell patients they have a right to look after themselves and they should exercise that right.

Dr. Gonder-Frederick: Patients aren’t taught adequately about the window of opportunity for self-treatment – if they miss that window, they could get themselves into real trouble. Neuroglycopenia is another important topic for family members to understand. I’ve worked with families where the parents are troubled by behaviors their children exhibit during a hypoglycemic episode, and they simply don’t understand that the patient was unable to control behavior during that time.

Dr. Amiel: One thing parents too-often do is over-treat hypoglycemia. It’s best to teach avoidance strategies (especially situational ones – after exercise, for instance) and to teach what causes hypoglycemia so that people can more successfully prevent it.

Novel Therapies for Type 1 Diabetes

Is There Any Role for SGLT-2 Inhibitors in Type 1 Diabetes?

Kathleen Wyne, MD (Ohio State, Columbus, OH) & Mick Kumwenda, MD (NHS Trust, North Wales, UK)

In an engaging debate on the use of SGLT-2 inhibitors in type 1 diabetes, Dr. Kathleen Wyne pointed to the profound weight loss, decrease in blood pressure, and opportunity to educate patients on euglycemic DKA (arguing pro) while Dr. Mick Kumwenda underscored the DKA risks and lack of sufficient evidence on SGLT-2 inhibitors in type 1 patients (arguing against). Dr. Wyne’s position centered around the notion that with proper education – in particular, on managing DKA risk and staying hydrated to avoid genital mycotic infections – a patient with type 1 diabetes can reap major benefits from an SGLT-2 inhibitor, namely A1c reductions, weight loss (which is becoming even more important with the growing prevalence of “double diabetes”), decreased blood pressure, less hypoglycemia, and a lower required dose of insulin. Notably, we’ve heard this opinion from other leading diabetes thought leaders as well, including Drs. Jeremy Pettus and Anne Peters at ADA 2016. Dr. Kumwenda pointed out, however, that few of these improvements on health markers have been empirically-supported for a type 1 patient population – that is, a large majority of our data on SGLT-2 inhibitors is limited to type 2 diabetes. He cited a study published in Diabetes Care showing a significant risk for DKA adverse effects associated with canagliflozin (J&J’s Invokana) treatment in participants with type 1 diabetes. Besides, Dr. Kumwenda added, we don’t have sufficient high-quality diabetes education as it is, so we can’t necessarily rely on this in endorsing SGLT-2 inhibitor use in type 1 diabetes care. To this last point, we only hope that diabetes education continues to improve, as we view it a disservice to patients to restrict prescriptions of potentially helpful drugs based on a distrust in the education component. To date, we’re not sure how euglycemic DKA is being reported in studies, so we also look forward to more information on this. Above all, we’re excited to see continued conversation on this new class of agents. Dr. Wyne expressed excitement as well over Lexicon’s investigations of SGLT-1/SGLT-2 dual inhibitor sotagliflozin in type 1 diabetes, which we agree holds promise based on results from the inTandem clinical development program so far.

Lifestyle and Diabetes

Changing the Behavior

Martha Funnell (University of Michigan, Ann Arbor, MI)

Ms. Martha Funnell discussed some of the major behavioral challenges relevant to diabetes care and presented strategies to boost patient engagement. Like other diabetes thought leaders, Ms. Funnell was very negative about the term “noncompliance.” “Keep in mind that this is not a problem, it’s a symptom of a problem,” she stated, suggesting that one key piece of high-quality diabetes care is identifying the problem underlying the low patient engagement. She acknowledged the difficulty that endocrinologists and primary care physicians face when their patients don’t seem to be improving, which can make even the most confident healthcare provider feel like a failure. Overcoming this obstacle requires a change in mindset, recognizing that patients do want to lead a healthy life and reorienting one’s responsibility as the healthcare provider to find ways to ease the patient’s struggle. We’re always appreciative of commentary on the immense psychosocial support that’s necessary in optimal diabetes care, which is too-often overlooked in discussions of “noncompliance.” Ms. Funnell detailed many useful approaches to better communicating with patients, starting with a change in vocabulary to eliminate this antagonizing term (that change can’t come soon enough!). Her additional key points for communicating with patients to boost engagement are described below:

• Providers should adopt patient-centric communication that asks more questions and makes fewer declarative statements. Ms. Funnell suggested open-ended questions that pave the way for collaborative decision-making, so that patients and providers are coming up with a treatment plan together. Positive questions are just as important as negative ones – ask “what’s going well for you?” before “what do you hate the most about your diabetes?”.
• Providers tend to get excited about a path too early. Instead, they should remain solution-neutral to reinforce the patient’s participation in collaborative decision-making. The key message here, according to Ms. Funnell, is that the patient and provider are “in this together.” Patients feel more supported and develop a greater sense of self-efficacy when they’re given an active role in designing their care plan.
• Patients care more about how diabetes impacts their everyday life, and less about beta cell biology. While there’s a place for an explanation of beta cells in diabetes education, Ms. Funnell argued that the first priority in communicating with patients should be problem-solving for real-world situations. What are you going to do the next time there’s cake at a birthday party, or next Thanksgiving? On a similar note, she articulated the need to avoid medical jargon in talking to patients and their families.
• Compliance and adherence are not outcomes. Providers must recognize the complexity of the emotional and behavioral aspects of diabetes that influence decision-making, engagement, and self-management.
• Providers should communicate that diabetes management is NOT easy, but it IS worth it. “If we act like it’s easy, a patient’s struggle feels like a failure, and that’s immediately disheartening.” As Ms. Funnell put it, we’ve all started an exercise plan that doesn’t quite last, and members of the diabetes care team should use this to empathize with patients and offer psychosocial support.
• “The patient is an expert on his/her own life; I’m just an expert in diabetes. I value the patient’s expertise.” We especially appreciated this sentiment from Dr. Funnell, which underscores the fact that diabetes is just one components of patients’ lives and it’s important to make.

Nutrition and Diabetes Prevention

Jaakko Tuomilehto, MD, PhD (Dasman Diabetes Institute, Kuwait City, Kuwait), Amy Fisher (Montefiore Medical Center, New York, NY), and Anne Wolf (Anne Wolf & Associates, Charlottesville, VA)

A lively symposium on nutrition convincingly demonstrated the value of dieting in a macronutrient-selective (rather than macronutrient-eliminating) manner. All of the speakers converged on the notion that opting for unprocessed over processed carbohydrates (that is, whole grain, fruits, and vegetables instead of sugar) and unsaturated over saturated fats (that is, olive oil, nuts, and legumes instead of animal fat and butter) is equally effective – not to mention simpler – than rigorously restricting carbohydrates or fat altogether. Nutritionist Ms. Amy Fisher pointed out that popular diet strategies (low carb, low fat, vegetarian, vegan, paleo, etc.) are actually not as distinct as they appear, sharing a majority of crucial elements in common: limited refined starches, little added sugar, and no processed foods. She surmised her view on the ideal diet with a reference to author Michael Pollan’s famed mantra: “eat right, not too much, mostly plants.” On a similar note, leading dietician Ms. Anne Wolf (Anne Wolf & Associates, Charlottesville, VA) emphasized the importance of simply eating less, outlining evidence that dietary approaches such as low carb and low fat are essentially equivalent so long as caloric restriction is present. We are reminded of Dr. Donna Ryan’s (Pennington Biomedical Institute, Baton Rouge, LA) recommendation that the best diet is simply the one to which someone can best adhere.

• Perhaps the most surprising information to arise from this symposium came from Dr. Jaakko Tuomilehto’s (Dasman Diabetes Institute, Kuwait City, Kuwait) discussion of the Nordic diet. To parallel the famed Mediterranean diet, the lesser-known Nordic diet (heavy in root vegetables, cabbage, apples, berries, oats, barley, fish, and coffee) is associated with protection against cardiovascular disease and weight gain in RCTs. Dr. Tuomilehto attributes this in part to the high antioxidant and omega-3 content of these foods native to the northern European regions surrounding the Baltic Sea. Accompanied by an image of his own berry farm in his home country of Finland, Dr. Tuomilehto presented a JAMA article of his own to support the protective effects of coffee against type 2 diabetes. To the audible gasps of everyone in the audience, Dr. Tuomilehto revealed that women from Finland (the nation with the highest per capita coffee consumption) who drink >10 cups of coffee per day (!) have a 79% reduced risk of developing type 2 diabetes (HR 0.21; p<0.001; controlled for age, physical activity, BMI, smoking, education, and alcohol consumption). Less prolific coffee-drinkers also benefit from a type 2 diabetes risk reduction: 58% for women who drink 7-9 cups/day, 60% for those who drink 5-6 cups/day, and 27% for those who drink 3-4 cups/day. We’re glad to see evidence-based support for our own coffee habits!

Current Technology and Diabetes Prevention

Mobile Health Strategies to Promote Healthy Lifestyles

Ben Gerber, MD (University of Illinois, Chicago, IL)

Dr. Ben Gerber presented a skeptical view of mobile health solutions, pointing to the mixed evidence on effectiveness and the lack of empirical evidence on health outcomes (such as CV events). For example, the TEXT ME trial conducted in Australia (n=710) reported that with just four texts/week for six months, patients experienced statistically significant reductions in major risk factors for CV disease including LDL, blood pressure, physical activity, smoking, and BMI. However, similarly-designed studies of text messaging in the US and elsewhere have reported negative results, which leaves a question mark in the literature. Notably, Dr. Gerber mentioned that some pilot studies of text messaging were not as large as TEXT ME, explaining that further research could very well show convincing health benefits, especially when complemented by co-interventions. He maintained an optimistic opinion on the potential for mobile health strategies to enhance diabetes prevention and care, but suggested that we still have a ways to go in identifying optimal evidence-based approaches. Attrition is a common problem in mobile health studies – the recently-published TRIPPA trial found a dramatic decline in Fitbit wear post-intervention, with only 10-15% of participants still wearing the device one year out. Mobile health strategies have to find a way to circumvent attrition and maintain engagement. Dr. Gerber went on to list additional lessons learned from studies of mobile health: Text messages and equivalent alerts should be random rather than predictable to maximize impact on behavior change, and should ideally be relevant to personal context (though this greatly increases the complexity and cost of the approach). For certain desired behavior changes, such as healthier eating, mobile health alerts might incite craving, and should thus be carefully crafted to encourage mindful eating. Dr. Gerber ended his presentation on a positive note, referring to exciting work going on at Omada Health to bring evidence-based elements into new mobile health platforms. He reiterated that these DPP-related platforms could be effective tools for weight management, but that we should wait for long-term data on health outcomes before touting mobile health as a scientifically-grounded healthcare solution.

Social Media and Health Promotion

Deborah Greenwood, MD (Sutter Health, Sacramento, CA)

“A person with diabetes engages with her healthcare team only 0.007% of the time – that’s even less for someone with prediabetes.” Emphasizing that a majority of diabetes management is self-management, immediate past AADE president Dr. Deborah Greenwood presented social media as a powerful tool for the diabetes community. Foremost, Dr. Greenwood pointed out that social media is 24/7 – no matter the time of day or night, a patient can ask questions, receive feedback, and connect with others in the Diabetes Online Community (DOC). Since most patients spend a fraction of a percent of time with a healthcare provider, it’s important for them to have other reliable sources of psychosocial support, which is absolutely critical in diabetes self-management. This is only one on a list of many benefits to social media – Dr. Greenwood also discussed relationship-building (“diabetes can be lonely”), the sharing of ideas, motivation to cope, shared experiences to combat fear and stigma, culturally-appropriate support regardless of where you are in the world, and spreading health literacy. She acknowledged that social media use is currently more common in the type 1 community vs. the type 2 community and attributed this to greater stigma associated with the latter, though more research is ongoing on this front. As part of the iDOCr (International Diabetes Online Community Research Council), Dr. Greenwood and colleagues are developing research questions with the end goal of optimizing social networking conversations. This program will hopefully address many of the challenges associated with social media for the diabetes community as well – Dr. Greenwood mentioned privacy issues, ensuring the quality and validity of information shared, the current lack of models to evaluate social media platforms, and the digital divide that exists for elderly and minority populations. We look forward to seeing what comes out of the iDOCr, as we agree that more research into optimizing social media would be extremely beneficial for global diabetes care. We so applaud Dr. Greenwood herself for her incredible social media interaction.

• Dr. Greenwood urged WCPD attendees to engage with social media platforms as well. She reminded everyone of the official conference hashtag – #WCPD9 – and suggested that if you’re new to social media, conferences are a great place to start!

Prevention of Diabetes Complications

Late-Breaking Clinical Trials

Dr. Abraham Thomas (New York University Langone, New York, NY)

In a highly-anticipated WCPD tradition, Dr. Abraham Thomas presented a rapid-fire overview of the very latest clinical trial results in the field of diabetes prevention. These trials, all published within the past few months, covered a diverse range of topics, from studies of type 2 diabetes genetic risk to an examination of how city design affects diabetes and obesity rates in its citizens. Below are a few of the most notable from our view:

• A recent Lancet article determined that PCSK9 genetic variants known for their association with lower LDL cholesterol are also associated with an increased risk of type 2 diabetes, in addition to higher FPG and increased body weight and waist-to-hip ratio. No association exists between these PCSK9 variants and A1c, fasting insulin, or BMI. Many people with type 2 diabetes use PCSK9 inhibitors to reduce their cholesterol – a potential cause for concern if PCSK9 has diabetes-promoting effects. That said, statins are associated with a known increased risk for development of type 2 diabetes, but the benefits of their cholesterol reduction are widely considered to outweigh the risks. If the cardiovascular outcomes associated with PCSK9 inhibitors match their incredible LDL cholesterol reduction potency, we expect that risk-benefit ratio of the class will look good – that said, their use has been hugely limited to date even with those with FH. Furthermore, an increased risk demonstrated those with PCSK9 loss-of-function mutations does not necessarily predict an increased risk with PCSK9 inhibitor therapies. We hope the FOURIER CVOT for Amgen’s Repatha (evolocumab) will shed some light on the long-term effects of this PCSK9 inhibitor, although we recognize that the trial is not powered for diabetes outcomes.  We learned in an earlier talk by Dr. Robert Eckel (University of Colorado, Aurora, CO) that FOURIER’s results will likely be presented at ACC in March 2017. We remain hopeful that PCSK9 inhibitor may address some of the residual cardiovascular risk associated with diabetes.
• An analysis of the EMPA-REG OUTCOME published in NEJM , also presented simultaneously at ADA 2016, provided more insight into the renal protective effects of empagliflozin. Empagliflozin produced a 44% relative risk reduction in doubling of serum creatinine and a 55% relative risk reduction in incident renal replacement therapy. There was no significant difference in the rate of incident albuminuria between the empagliflozin (n=4124) and placebo (n=2061) groups.
• A JAMA study revealed that residents of more walkable neighborhoods had a significantly decreased ten-year incidence of both obesity and type 2 diabetes. Researchers scored nearly 9,000 Canadian neighborhoods with a validated index of walkability and tracked the citizens’ BMIs and diabetes incidence from 2001-2012. People’s leisure-time physical activity, diet, and smoking patterns were unrelated to their neighborhood’s walkability, but rates of walking and cycling were far higher in more walkable cities. These findings pointing to the importance of the built environment in mediating a certain degree of diabetes and obesity risk, underscoring the importance of efforts like Novo Nordisk’s Cities Changing Diabetes to confront the obesogenic environment that characterizes so many urban areas.
• Another JAMA study dissected the interaction between genetic and lifestyle risk factors for coronary artery disease. Rather expectedly, the combination of unfavorable genes and lifestyle produced the highest risk profile and the combination of favorable genes and lifestyle produced the lowest risk profile. Interestingly the combination of unfavorable genes and favorable lifestyle produced nearly the same risk profile as the combination of favorable genes and unfavorable lifestyle. In fact, lifestyle was so powerful to minimize the effects of genetic risk that among participants at the highest genetic risk, a favorable lifestyle produced a nearly 50% lower relative risk of coronary artery disease.

The Status of Diabetes Prevention in the United States

The Epidemiologic Case and Landscape of Diabetes Prevention

Edward Gregg, MD (CDC, Atlanta, GA)

The CDC’s Dr. Edward Gregg pushed for risk stratification within the prediabetes population, so that intervention occurs more swiftly and aggressively in subsets at high-risk for type 2 diabetes vs. subsets at lower-risk. “Diabetes is a big enough problem that it really calls for a multi-tiered response,” Dr. Gregg asserted, presenting risk stratification as an important step to making prevention cost-effective and feasible on a large scale. This matches a recurring message we heard at this meeting: 86 million Americans with prediabetes is simply too many people to treat haphazardly – the prevention question must be approached systematically, with cost-effectiveness in mind (see our coverage of Dr. John Buse’s presentation from WCPD day #1). The top decile of individuals with prediabetes have an A1c between 5.8-6.5%, and this top 10% accounts for ~29% of new type 2 diabetes cases over 10 years. The top 20% of the prediabetes population, with A1c between 5.6-6.5%, accounts for a little over half of all new type 2 diabetes cases over 10 years. Therefore, treating this tier of the prediabetes population – at high risk for type 2 diabetes – is most pertinent because it will have maximum impact in lowering diabetes prevalence. According to Dr. Gregg, this high-risk cohort should be enrolled in the Diabetes Prevention Program (DPP) or a similar evidence-based lifestyle intervention to delay or prevent new-onset type 2. Meanwhile, the middle- and low-risk tiers of the prediabetes population should be targeted with a broader-reach, lower-intensity (and in effect, less expensive) intervention – telephone counseling, for instance, or a more hands-off educational platform that encourages lifestyle changes to mitigate type 2 diabetes risk factors. On a related note, Dr. Gregg spoke to the cost-effectiveness and overall efficacy of metformin as a prediabetes intervention (reducing type 2 diabetes incidence by 31%), again echoing Dr. Buse’s view. However, he remarked that a disappointingly-low 3-7% of individuals with prediabetes are taking metformin. While he has observed a noticeable increase in the practice of lifestyle intervention as a preventative strategy, the same increase is not being seen for metformin – perhaps a prediabetes indication from the FDA would sway this?

Lessons from the Field on the Efficacy and Cost of Primary Prevention

Mohammed Ali, MD (CDC and Emory University, Atlanta, GA)

Dr. Mohammed Ali discussed the effectiveness and economics of translating the Diabetes Prevention Program (DPP), pointing to opportunities for wide impact even if resources are limited. Based on the empirical evidence, there’s no doubt that the DPP is effective, but Dr. Ali explained that various aspects of the original trial intervention program might be considered too costly, especially in under-resourced areas. The expenses associated with paying the salary of a healthcare professional administering the 16 sessions of the program and delivering the program in-person, to individuals rather than groups are two examples. Showcasing data from a recent meta-analysis, which pooled data from 44 heterogeneous implementations of the DPP (n=8,995 individual participants) in US settings, Dr. Ali argued that group-based delivery  for the program was just as effective as individual delivery. Despite a smaller number of sessions offered (12.6 on average) vs. the traditional DPP (offering 16), and despite mean attendance being only 11 sessions, mean weight loss was ~4 kg across all studies analyzed and A1c dropped an average -0.2%, both of which could be clinically-meaningful for an individual with prediabetes. Other risk factors also showed meaningful improvement: fasting blood glucose declined by a mean 2.4 mg/dl, systolic blood pressure decreased ~4 mmHg, HDL levels rose ~1 mg/dl, and total cholesterol fell ~5 mg/dl. Above all, these adaptations of the DPP demonstrated efficacy at a quarter of the cost: whereas the traditional DPP costs $100 per participant per session, the mean cost of delivering the intervention in translation studies was $25 per participant per session. Based on these results, Dr. Ali emphasized that lower-cost iterations of the DPP can indeed be effective in lowering diabetes risk factors. He acknowledged the limitation that this analysis could not evaluate whether type 2 diabetes incidence would be reduced, but the proof of principle that lifestyle modification delays diabetes onset in high-risk individuals has already been demonstrated in the DPP, DPS, and other large efficacy trials.

• To create a prevention program on a budget, Dr. Ali suggested training laypeople to administer lifestyle intervention sessions, group-based interventions, and exploring alternate channels such as an online DPP platform. We certainly appreciate the need for cost-effectiveness analysis in a conversation on population-level diabetes prevention, and we’d be interested to see more data on DPP translations. We note that the traditional DPP itself has been shown to be cost-saving over time. That said, we think it’s so important to have a variety of effective prevention solutions for different areas with different base resources, and we were glad to learn Mr. Ali’s perspective on feasible, still-effective, quality-controlled, low-cost prevention strategies.

International Prevention Programs

Moving Forward with Tobacco Prevention in Finland

Mervi Hara (Suomen ASH, Helsinki, Finland)

We heard fascinating insights from Ms. Mervi Hara, executive director of Finland’s Suomen ASH (Action on Smoking and Health) smoking prevention program, on lessons learned from the successful implementation of a prevention-centered public health campaign. Smoking doubles the risk of type 2 diabetes and increases the risk of diabetes complications, so anti-tobacco campaigns function as indirect diabetes prevention initiatives. Beyond that, the success of smoking prevention campaigns around the world provides a model for how diabetes prevention campaigns should be designed. At the very least, we might gather important tips from anti-smoking efforts on what works and what pitfalls to avoid. Finland’s smoking prevention campaign is a paradigm – nearly 80% of Finnish men smoked in the 1950’s, and now Finland has the lowest smoking rate in Europe. Below are some of Ms. Hara’s major pieces of advice on what made Suomen ASH so successful, and what should be gleaned for diabetes prevention efforts:

• The goal of a prevention program is not to restrict unhealthy behavior, but to foster an environment where people do not want to engage in unhealthy behavior. Ms. Hara emphasized that achieving the “endgame” of zero tobacco use was not matter of prohibition, but of behavior change. The tobacco prevention movement in Finland took decades of gradual change in public knowledge, attitude, and policy, and a successful nationwide diabetes prevention effort will likely require a similar collaboration between forces.
• A successful prevention programs operates at both the individual and population level. Individuals should have easy access to educational resources on heathy behaviors and to workshops or coaches for behavior maintenance. These facets work best when complemented by policy and regulation at the population level to guide people toward healthy choices (for instance, taxation on tobacco or soda).
• An effective way to win over policy-makers is to frame prevention as an investment that reduces avoidable health expenses. Suomen ASH relied on the message that tobacco control is an investment in Finland’s future, as consequential and important as technological development, infrastructure, or education. Ms. Hara recalled that calculations of the economic costs of smoking were quite convincing to Finnish politicians, and the same would likely be true for diabetes. As she put it, “money is a good consultant.”
• In the Finnish smoking prevention campaign, arguments against tobacco companies were more compelling to the public than were arguments about the health consequences of smoking. Despite the abundance of evidence to support the adverse health effects of tobacco, Ms. Hara explained that the Finnish population responded much more fervently to messaging about the tobacco industry’s tactics to manipulate consumers into buying harmful products. Instead of “don’t smoke, it’s unhealthy” (a message that is perhaps too commanding and contains information that people already know), Suomen ASH flipped the script to instead warn Finns that they were being unknowingly manipulated into buying tobacco products via pervasive advertising campaigns and prominent presence in stores. We can envision a parallel situation in the US – instead of commanding people to eat more healthy food, perhaps we should be alerting people to the toxic food environment perpetuated by the food and beverage industries.

Finnish Diabetes Prevention Program Update

Jaakko Tuomilehto, MD, PhD (Dasman Diabetes Institute, Kuwait)

The esteemed Dr. Jaakko Tuomilehto (Dasman Diabetes Institute, Kuwait) provided an update on the Finnish Diabetes Prevention Study (FIN DPS) that showed a 58% diabetes risk reduction. Largely in parallel to the well-known DPP in the US, FIN DPS randomized middle-aged Finnish individuals at high-risk for diabetes (n=522) to receive either usual care (general dietary and exercise advice) or an intensive lifestyle intervention in the form of individualized nutrition counseling and exercise training. In support of the effectiveness of diabetes prevention programs, the intensive lifestyle intervention reduced the risk of diabetes by 58% (the same risk reduction seen with DPP). At a more granular level, the lifestyle intervention program produced long-term benefits in weight reduction and a variety of glycemic measures. At one- and three-year follow-ups, the intervention group showed an average weight reduction of 4.5 kg and 3.5 kg, respectively (compared to 1.0 kg and 0.9 kg in the control group). Similarly, A1c in the intervention group fell 0.1% in the first year and 0.2% in the third year (versus +0.1% and 0% in the control groups, respectively). This study was prematurely terminated in 2000 since the effectiveness of the intervention was so overwhelmingly apparent – if that isn’t a resounding endorsement for intensive lifestyle intervention as a type 2 diabetes prevention tactic, we don’t know what is!

• Several FIN DPS follow-up analyses have examined whether the effect of lifestyle intervention was modified by an individual’s genotype. Polymorphisms in the FTO gene (associated with increased fat mass and obesity risk) do not modify the effect of lifestyle intervention: Although individuals with the high-risk AA genotype at SNP rs9939609 entered the study with a higher BMI than participants with the lower-risk AT and TT genotypes (p=0.006), all groups experienced a similar magnitude of weight reduction. Encouragingly, this implies that even individuals with obesogenic genetic profiles can very effectively improve outcomes with lifestyle modification. Moreover, a separate study investigating general family history of diabetes (encompassing 19 known genetic risk loci) determined that the lifestyle intervention was similarly effective at preventing diabetes in those with a family history of diabetes and those without.

US National Diabetes Prevention Programs

Lawrence Philips, MD (Emory University, Atlanta, GA)

Local expert Dr. Lawrence Philips (Emory University, Atlanta, GA) argued for a more rigorous approach to glucose control in prediabetes and early diabetes. Pointing out the well-known evidence that better glucose control sustains beta cell mass and function, supports the delay and prevention of diabetes progression, and produces a “legacy effect” of years of sustained better control, Dr. Philips questioned why we are not treating prediabetes and early diabetes more aggressively, to mitigate the severity of diabetes later on. He presented a simple framework for how our practice should change: (i) more routine screening to recognize prediabetes earlier and more reliably; and (ii) rigorously strive to keep glucose levels in the normal range, using a combination of lifestyle modifications, metformin, and even other agents such as DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, or alpha-glucosidase inhibitors, along with early initiation of long-acting insulin, if needed. Effective prediabetes management represents an opportunity to change the natural history of diabetes, and Dr. Philips’ message comes as both a wakeup call for taking prediabetes and early diabetes more seriously and as a cause for optimism that the progression of diabetes can be dramatically mitigated.

Panel Discussion

Sudhirsen Kowlessur, MD (Ministry of Health and Quality of Life, Port Louis, Mauritius); Lawrence Philips, MD (Emory University, Atlanta, GA); Jaakko Tuomilehto, MD (Dasman Diabetes Institute, Kuwait); Mervi Hara (Suomen ASH, Helsinki, Finland)

Q: How do you scale the population approach to prevention in the real world?

Dr. Tuomilehto: We need to have political will. Clinical trials give us proof, but the second step is to convince the political agent of this and make real plans. I’m not saying it is unnecessary to have prevention clinics and coaches, but this is an impossible way to tackle the problem in the long term. Imagine trying to end the smoking epidemic with only clinics! Who will start the leadership to scale our prevention efforts? We need examples like tobacco legislation to get started.

Q: What was involved politically in the plan to end tobacco? What did it take (and what is it taking) to get political will behind this?

Ms. Hara: It took tears and sweat. You have to find key people. You don’t need all the politicians behind you, but you do need the help of leading and charismatic politicians. In Finland we contacted people in the government and in the Ministry of Health. Our calculations about the costs of smoking were quite convincing to them. Money is a good consultant.

Q: What is the common denominator for change?

Ms. Hara: The critical element is that we could ruin the tobacco industry’s reputation by showing how they lie and manipulate consumers. The media was on our side with this, and then the politicians realized it was a popular position to take.

Q: Was there opposition to the Finnish anti-tobacco campaign?

Ms. Hara: The tobacco industry and their allies. And they are very clever.

Q: What did you do to get politicians on board with the diabetes prevention efforts in Mauritius?

Dr. Kowlessur: The government and Ministry of Health and Quality of Life is putting a lot of emphasis on non-communicable disease prevention, especially diabetes. The way we achieved this was by showing politicians that good health is a huge investment. Our main resource in Mauritius is our people.

Q: In the US (and probably a lot of other places) people tend to blame type 2 diabetes on individual choices. I imagine something could happen with lung cancer as well (“you gave this to yourself by smoking”). What can we learn from the anti-tobacco movement about not blaming the individual and instead blaming industry advertising, etc.?

Dr. Philips: There are no easy answers. There will always be individual choices, but money has a lot to do with the opposition. For example, we want to get healthier foods into our schools, but schools get money from the soda machines. There is pervasive advertising in every aspect of the media, and the food industry is very good at making foods that we will like and continue to eat and drink. Money, especially in the US, has a lot to do with political will. I think to solve this you have to follow the money and find out the fabric of the opposition. 

Q: Is it possible to tax tobacco or unhealthy food out of existence? Would a black market develop? The US stopped prohibition because there was so much criminal activity associated with black market alcohol products. The cure was worse than the disease. What is Finland learning in the attempt to politically prohibit all tobacco products?

Ms. Hara: We are not going for prohibition; and it is important that people understand that. Our goal is to create an environment where people do not want to make the choice to smoke. Nothing in terms of a tobacco black market has appeared so far in Finland.

Debate Session

The Best Medication to Prevent Type 2 Diabetes

Guillermo Umpierrez, MD (Emory University, Atlanta, GA), Simon Heller, MD (University of Sheffield, UK), and Jason Baker (Weill Cornell Medicine, New York, NY)

The highly-regarded Drs. Guillermo Umpierrez, Simon Heller, and Jason Baker took the stage during a debate session to argue for metformin, GLP-1 agonists, and alpha glucosidase inhibitors as the best medication to prevent type 2 diabetes, respectively. Dr. Umpierrez focused on the trifecta of efficacy, safety, and cost, suggesting that metformin is the only drug that currently checks all three boxes. While data shows that metformin therapy lowers the risk of new-onset type 2 diabetes by 31% compared to a 58% relative risk reduction with intensive lifestyle intervention, he pointed out that diabetes incidence in these two groups becomes highly similar with a longer-term view: At 10 years, 47% of metformin participants have type 2 diabetes vs. 42% of lifestyle participants; at 15 years, 56% of metformin participants have type 2 diabetes vs. 55% of lifestyle participants. Importantly, Dr. Umpierrez underscored the cost effectiveness of metformin: by his calculations, metformin costs ~$50 vs. ~$1,500 for a standard 16 sessions of intensive lifestyle intervention and ~$1,100-$3,200 for GLP-1 agonist therapy. Dr. Heller had to concede on the cost argument: “It’s certainly hard to argue that a drug so expensive is the best option,” he admitted, “but in terms of efficaciousness, nothing else comes close to GLP-1 agonists.” He highlighted SCALE data on the efficacy of high-dose liraglutide (Novo Nordisk’s Saxenda) in preventing type 2 diabetes. He also discussed the importance of cardiovascular (CV) outcomes data, particularly from the LEADER trial, which demonstrated that liraglutide (Novo Nordisk’s Victoza) reduces risk for CV events including stroke, MI, and death by 13% (p=0.01 for superiority). We appreciated Dr. Heller’s commentary that we should be thinking about CV protection early on over the course of diabetes management, perhaps even as early as a prediabetes diagnosis. We’ve noticed movements in the field toward a greater emphasis on CV outcomes – in fact, we think a new diabetes drug would be hard-pressed to find success without demonstrated cardioprotection at this point. We were happy to hear that J&J has a CVOT planned to investigate SGLT-2 inhibitor Invokana (canagliflozin) in a prediabetes population, which matches Dr. Heller’s suggestion that we consider CV outcomes earlier on. Candidly, we were swayed by both arguments. Short-term, we hope to see metformin more widely-used as a prediabetes intervention given its low cost and proven efficacy. Longer-term, we’ll be waiting eagerly for CV outcomes data on GLP-1 agonists in people with prediabetes, and we’d love to see more cost-effectiveness analysis on GLP-1 agonists for prediabetes as well – these advanced agents are surely effective in promoting weight loss and glycemic control, so we only hope that patient access barriers are overcome and that more people can benefit from their preventative effects.

• Dr. Baker discussed the “overlooked” preventative benefits of alpha glucosidase inhibitors, though Dr. Umpierrez rebutted that low adherence to these agents makes them less effective than metformin. We heard commentary to the same effect at CMHC 2016, when ADA’s Dr. Robert Ratner pointed out the low prescription volume of alpha glucosidase inhibitors in the US, attributing the phenomenon to unwanted GI side-effects such as flatulence, which hold more weight in patients’ minds than the possible long-term health benefits. From our view, it certainly seems like lifestyle intervention, metformin, and GLP-1 agonists will remain at the center of prevention conversations.

Women with Diabetes and Prediabetes

Babies of Diabetic Women, Are They at Higher Risk for Future Diabetes?

Jason Baker, MD (Weill Cornell Medicine, New York, NY)

Dr. Jason Baker discussed the increasing incidence of gestational diabetes and the additional risk of diabetes that this confers to babies. Worldwide, ~16% of pregnancies involve a mother with diabetes, and gestational diabetes accounts for 85% of this. Dr. Baker pointed to two worrisome findings: (i) the incidence of gestational diabetes is steadily rising; and (ii) children of mothers with gestational diabetes are more likely to develop type 2 diabetes. Evidence for this second point comes from a longitudinal study of the Pima Indian community in Arizona, the society with the world’s highest prevalence of type 2 diabetes. Researchers followed 911 Pima mothers and 1,436 of their children from age 0-39. For every ~23 mg/dl increase in maternal glucose, the child’s birth weight increased by 56 g (p=0.0002) and the child’s risk of diabetes increased by 60% (p<0.0001). This finding supports the notion that diabetes begets diabetes – mothers with diabetes or gestational diabetes tend to have children who also develop diabetes, spurring a vicious cycle. Dr. Baker pointed out that the rise of gestational diabetes is likely due to a combination of increasing obesity prevalence, older gestational age, and more frequent gestational diabetes screening. However, the reasons underlying the increased type 2 diabetes incidence in the offspring of mothers with gestational diabetes are less clear. Dr. Baker hypothesizes that the in-utero environment may pre-program these children for beta cell dysfunction – an idea currently under investigation.

-- by Abigail Dove, Payal Marathe, Helen Gao, and Kelly Close