- Diabetes therapy: Endo Fellows 2018 has already offered incredible learning, in just one full day of the agenda! Hypoglycemia expert Dr. Elizabeth Seaquist touted the benefits of Novo Nordisk’s next-gen Tresiba (insulin degludec) for hypo risk reduction. She shared data to show that hypoglycemia is equally frequent across a range of A1cs – <7% and >10% – which means relaxing A1c goals is not an effective means of avoiding lows (is ACP listening? The Joslin’s Dr. Medha Munshi also proved this a year ago in Diabetes Care in an already often-cited paper “Liberating A1C goals in older adults may not protect against the risk of hypoglycemia”). Conference co-chair Dr. Irl Hirsch delivered a talk on old and new insulins, admitting that he can’t speak on this topic without mentioning the outrageous skyrocketing of insulin cost. In fact, much of his presentation focused on best practice for prescribing human insulin, since “the number of patients on human insulin is only going to grow in the next few years.” (Well, yes, not just due to pricing but also the sheer volume of people staying older longer and needing insulin plus the high number of patients whose therapy has needed to intensify to insulin for some time!) Dr. Guillermo Umpierrez shared overall positive commentary on the prospect of SGLT-2s in type 1 (we’re getting more and more excited about this, now that AZ has filed dapagliflozin for type 1 in Europe – DKA is manageable and we’d love to see greater education), and Dr. Carla Greenbaum discussed an impending paradigm shift in type 1 diabetes care, a transition from treating the symptoms of hyperglycemia to addressing the underlying autoimmunity.
- Diabetes technology: Dr. Guillermo Umpierrez urged fellows to engage in research investigating diabetes technology use in the hospital setting; 7.2 million patients with diabetes are discharged from US hospitals each year, and yet the prevalence of hypoglycemia in hospitalized type 1 patients is unknown. Dr. Umpierrez sees a “limited future” for CGM use in the ICU, but does remain optimistic regarding the benefits in the non-ICU setting. We also attended a fascinating breakout session on pump therapy led by Dr. Janet McGill, during which we were disappointed to learn that come April, Medicare pump guidelines will become even stricter, demanding two-months of data demonstrating four fingersticks per day. She also shared mixed views on the 670G.
- Big picture: The big picture highlights in this report are truly not-to-miss. On Tuesday evening, author Mr. Jim Hirsch (Dr. Irl Hirsch’s brother) delivered a powerful keynote, detailing his experience living with type 1 diabetes and raising a son with type 1 diabetes. On Wednesday evening, Dr. Robert Eckel and his family (wife Margaret, son Clark, and daughter-in-law Jami) shared their unique story with type 1. Both sessions covered similar and all-important themes – that HCPs must acknowledge and address the complicated psychology that comes with this diagnosis, that patients must be shared decision-makers, that good diabetes care minimizes interference in life (especially for children and adolescents), and that people can live a long and healthy life with type 1 diabetes today.
Hi from Chi-Town! We’re in Chicago this week for the annual Endocrine Fellows meeting on type 1 diabetes, to be followed by ENDO 2018 beginning Friday. This report is our first installment of highlights from these back-to-back conferences. As you scroll down – or click through the table of contents – you’ll find highlights on diabetes therapy, diabetes technology, and big picture talks on the experience living with type 1 (from renowned author Mr. Jim Hirsch and Dr. Robert Eckel & family).
For a glimpse at what’s to come, see our full conference preview. Now, without further ado...
- Diabetes Therapy Highlights
- 1. Hypoglycemia Crash Course with Dr. Seaquist: Hypo Occurs Across Range of A1cs; Tresiba’s Hypo Benefit; 30-Year DCCT Follow-Up Will Elucidate Correlations Between Hypoglycemia/Cognitive Decline
- 2. Dr. Hirsch on Increasing Use of Human Insulin, Offers Practical Tips; Impressed by Tresiba + Afrezza, Less So by Fiasp
- 3. Dr. Umpierrez Cautiously Accepts SGLT-2 Inhibitors for Type 1 Diabetes; Offers Valuable Insight on DKA Causes and Treatment Protocol
- 4. Dr. Greenbaum Shares Hope for Future of Disease-Modifying Immune Therapies in Type 1 Diabetes
- Diabetes Technology Highlights
- Big Picture Highlights
- 1. In Powerful Keynote, Author Jim Hirsch Tells His and His Son’s Type 1 Diabetes Story, Illustrating the Impact of Diabetes on Individuals and Families
- 2. Dr. Robert Eckel and Family on Tips and Tricks from 80+ Collective Years of Type 1 Diabetes Experience; Emphasis on Shared Decision-Making and Meaningful Patient/Provider Interactions (Dr. Hirsch Even Proposes a Study)
- Detailed Discussion and Commentary
Diabetes Therapy Highlights
University of Minnesota’s Dr. Elizabeth Seaquist gave a crash course in hypoglycemia, describing causes, consequences, and evidence-based treatment options for this far-too-common complication of diabetes. According to a 2015 study from Leicester’s Dr. Kamlesh Khunti and colleagues (n=27,585), 14% of type 1s experienced severe hypoglycemia in one month of prospective follow-up, while 83% experienced any hypoglycemia. Among type 2 patients, the rate of severe hypo was 9% and the rate of any hypo was 47%. Dr. Seaquist highlighted the “striking” consistency in frequency of hypoglycemia around the world (the study covered 24 different countries). She also pointed to T1D exchange data showing that ~12% of type 1s in the US had severe hypoglycemia in the past 12 months. Considering these results in sum, Dr. Seaquist asserted, “I think we can say this is an extremely common event in patients with type 1 diabetes.” She emphasized that fear of hypoglycemia is equally pervasive. A recent survey in Japan found that 27% of type 2s had a high measure of fear of hypoglycemia. Dr. Seaquist touched on the “immobilizing distress” that stems from this fear: “All of you have probably talked to patients who would do anything possible to avoid hypoglycemia, even at the expense of good glycemic control and microvascular risk reduction.” Separately, we’ve heard that 79% of type 1 patients and 58% of type 2 patients lower their insulin doses following a severe low, so we can certainly see how this fear leads to suboptimal diabetes management overall. In our view, perhaps the most important slide in Dr. Seaquist’s presentation showed that severe hypoglycemia is just as common for people with high A1c (8%-9% or even ≥10%) as it is for people who reach target A1c 6.5%-7% or ≤6.5%. This corroborates findings from Joslin’s Dr. Medha Munshi that high A1c is not protective against hypoglycemia, but is rather indicative of more time spent out-of-range, and it makes it all the more disappointing that the American College of Physicians (ACP) recently recommended raising A1c goals to 7%-8% for the majority of type 2s as a way to avoid hypoglycemia (as well as weight gain and high cost of treatment). Notably, Dr. Seaquist’s slide used T1D exchange data in type 1s, while Dr. Munshi’s paper and the ACP guidelines apply to type 2, but the same key message holds true across the spectrum of diabetes care – we should not be relaxing glycemic goals for everyone (although this may be appropriate in specific circumstances), because this only perpetuates hyperglycemia and doesn’t necessarily reduce hypoglycemia.
- What does reduce hypoglycemia? Dr. Seaquist reviewed prevention/treatment strategies in rapid-fire fashion, though there was more discussion of this during Q&A (see below). She highlighted the hypoglycemia benefit of newer basal insulins, particularly Novo Nordisk’s Tresiba (insulin degludec), which demonstrated significant risk reduction for severe hypo vs. Sanofi’s Lantus (insulin glargine) in the SWITCH studies as well as the DEVOTE CVOT. Tresiba received a hypoglycemia claim from EMA in 3Q17, and Novo Nordisk is expecting a decision from FDA on updating the US label by end of 1Q18. Dr. Seaquist praised Tresiba’s flexible dosing, a meaningful advantage for quality of life. “We have better insulins now, and shouldn’t put patients on regimens that require regular eating if we can avoid it. I don’t eat on a regular schedule. Do any of you? Why should we ask our patients to?” Glucagon prescriptions should always come alongside insulin prescriptions for people with type 1, Dr. Seaquist stated – but beyond that, she underscored the importance of educating and re-educating family members and caregivers on administering glucagon from emergency kits, which aren’t easy to use in stressful situations. A loved one experiencing severe hypoglycemia that requires assistance is, by nature, an exceptionally stressful situation. Although not mentioned in this talk, we expect nasal glucagon (from Lilly) and liquid-stable glucagon in pre-filled pens (from Zealand and Xeris) to play a big role here, provided cost and reimbursement are reasonable once these next-gen products reach the market. Dr. Seaquist presented real-world data on Lilly’s nasal glucagon at ADA 2017, and very notably, 98% of caregivers successfully delivered a full dose within two minutes (70% did so within 30 seconds!). For patients who can access/afford it, Dr. Seaquist recommended CGM, since monitoring itself is often sufficient to prevent hypoglycemia; we just saw HypoDE results at ATTD demonstrating that CGM significantly lowers hypoglycemia rate in type 1s with hypo unawareness previously on MDI. Dr. Seaquist shared similar positive commentary on AID with threshold suspend as a means of minimizing hypoglycemia. She listed structured education as another effective risk reduction strategy (briefly discussing DAFNE) and highlighted this 2016 paper by Dr. Michael Rickels et al. on the benefits of islet transplant for type 1s experiencing recurrent, problematic hypoglycemia.
- The 30-year follow-up on DCCT participants includes a battery of cognitive assessments, and Dr. Seaquist suggested that this will be the best data yet on how hypoglycemia affects cognitive function. In the original DCCT, hypoglycemia did not show a significant association with accelerating cognitive decline, but Dr. Seaquist noted that patients starting this study were relatively young, with a mean age of 27. She also called attention to a small study of experimentally-induced overnight hypoglycemia, which enrolled adults with and without diabetes; in both cohorts, nocturnal hypo was associated with poorer performance on a memory recall task. The implication is that perhaps a night of hypoglycemia decreased sleep-associated consolidation of declarative memory. That said, Dr. Seaquist underscored that we need higher-quality data in a larger sample size before we can form conclusions about the hypo/cognition connection. We look forward to 30-year learnings on this topic from the DCCT.
- Dr. Seaquist summarized recent consensus statements on hypoglycemia, sharing hope that more clinical trials of new diabetes drugs will make use of the agreed-upon definitions. This consensus is exciting, Dr. Seaquist explained, in that it should encourage manufacturers to demonstrate hypoglycemia benefit from their advanced therapies. She outlined how hypoglycemia risk reduction should be a priority in clinical practice, and should be an endpoint in clinical trials. We couldn’t agree more, and we add that we’d like to see more CGM in diabetes clinical research, to show benefit on glycemic outcomes beyond A1c – hypoglycemia, time-in-range. As the bar rises for new diabetes therapies, lowering A1c is simply not enough, and the consensus on hypoglycemia (alert level 1 <70 mg/dl, level 2 <54 mg/dl, and level 3 classified as a severe event requiring assistance) opens the door for drugs to show more.
Select Questions and Answers
Dr. Irl Hirsch (University of Washington, Seattle, WA): This may not be relevant to pediatricians in the room, but in my practice, I see so many patients with longer duration of diabetes. Hypoglycemia prevention is actually the no. 1 priority in these patients. Dealing with someone who has been on an insulin pump for 20, 25, 30, 35 years is very different from dealing with someone who’s 15 years-old or 10 years-old on a pump, because of fibrosis under the skin. Maybe we can’t see it, but we know it’s there. The flow from an insulin pump is so variable, and this becomes a major problem. Many of my patients don’t want to go back to MDI. I’m convinced – though I have no formal data on this – that with newer insulins, especially degludec but also U300 glargine, these patients do significant better than they did with their pump because the advanced basal insulin is so consistent day-to-day. I’d like to see this clinical trial.
Dr. Seaquist: I agree. Insulin degludec, in particular, is a really wonderful option for this population.
Dr. Linda Siminerio (University of Pittsburgh, PA): I see with pediatric patients, our tendency is to automatically go glucagon, glucagon, glucagon. But I had a neighbor, and I was going over all the time because he had hypoglycemia unawareness, and he didn’t have glucagon. I’d like to stress to the adult fellows in the room that glucagon is super important.
Dr. Seaquist: There was a study where researchers set up a mannequin with a backpack nearby holding an emergency glucagon kit, and less than half of family members who had been instructed in how to use this were able to use it effectively in the simulation and get a full dose in. These emergency glucagon kits are not easy to use. So, it’s really important to re-educate people, and to update families and caregivers as well.
Insulin therapy is moving in fast-forward and rewind at the same time, according to UW’s Dr. Irl Hirsch. On the one hand, next-generation insulins offer better patient experience and outcomes (Dr. Hirsch mentioned Novo Nordisk’s Tresiba and Fiasp, Sanofi’s Toujeo, MannKind’s inhaled Afrezza). But on the flip side, as insulin prices skyrocket, more patients with diabetes are going back to human insulin. Dr. Hirsch predicted that this number will only increase in the next two-three years, and he thus urged endocrinology fellows to become familiar with best practices for prescribing human insulin. He walked through several “clinical pearls,” starting with injection site for human insulin (the abdomen is preferable to arms, which are preferable to thighs, which are preferable to the buttocks). He explained that snacking may be necessary, especially before bed to avoid nocturnal hypoglycemia, and he recommended consistency of dose timing and carb intake each day. Notably, Dr. Hirsch described patients who can’t afford an insulin analog but who can afford CGM – “how crazy is that?!” The bright side is that CGM can be of great assistance to someone on human insulin, even if only used occasionally or professionally to track glucose patterns and hypoglycemia – this risk is substantially higher with human insulin as opposed to insulin analogs. As Dr. Hirsch put it, “you can use 2018 technology with 1980s insulin” (that’s a quote that will stay with us for quite some time…). Well-known by now for his strong opinions on outrageous insulin prices and his willingness to speak up about them, Dr. Hirsch also co-authored a JAMA viewpoint last year with practical advice on prescribing human insulin in type 2 diabetes. We appreciate the clinical wisdom and the important commentary; we do understand that profitability for insulin has been declining for some time. At the same time, there are manufacturers that are reducing prices for other drugs (for example, Merck/Pfizer and SGLT-2 pricing) and with drugs like Lilly/BI’s Basaglar doing so well, we would expect profitability to continue to decline as we see an urgent need to address the pricing issues throughout healthcare (for example, we’d love to see pricing data on dialysis, etc.), and soon.
- “I don’t like doing this. I don’t even like giving this talk. But I have to, because the number of patients on human insulin is only going to grow in the next few years.” Dr. Hirsh was pleasantly surprised when ~half the people in the room said they had received at least some training on human insulin through their endocrinology fellowship. That said, this percentage should be even higher (it should be all fellows!), especially considering that a majority of conference attendees are adult fellows rather than peds fellows.
- Dr. Hirsch was quite positive about Tresiba (insulin degludec) and Afrezza, although he was underwhelmed by the data on Fiasp (faster-acting insulin aspart). First, on Novo Nordisk’s next-generation basal, he referred to the SWITCH 1 study which found significant hypoglycemia risk reduction for type 1s who switched from Sanofi’s Lantus (insulin glargine) to degludec vs. those who went from degludec to glargine. SWITCH 2 reported similar results in type 2 diabetes, and the DEVOTE CVOT showed Tresiba’s hypoglycemia benefit vs. Lantus in an even larger sample size of type 2 patients, adding to the robustness of evidence. Dr. Hirsch described very positive feedback from his patients on Afrezza, and he suggested that speed is the key factor leading to this high treatment satisfaction. “They love it because it’s fast,” he said, referring to Afrezza’s rapid onset/rapid offset, which leads to tighter glucose control and less uncertainty around meals. FDA granted Afrezza an ultra-rapid-acting designation late last year, specifically displaying faster onset/offset vs. Lilly’s Humalog (insulin lispro). We note that sales of the inhaled insulin product have been sluggish to-date (comprising <1% of the $1.6 billion/quarter rapid-acting insulin market), though this more so reflects commercial challenges at MannKind vs. safety/efficacy of the drug. Lastly, Dr. Hirsch shared his view that Fiasp data has “not been as impressive as we would have liked.” He claimed that faster aspart is “not nearly as fast as Afrezza.” He referred to Onset 5 results presented recently at ATTD, calling out that Fiasp only showed non-inferior A1c reductions vs. NovoLog (insulin aspart) over 16 weeks for type 1s on an insulin pump. We’d add that Fiasp did show significant benefit vs. NovoLog on one-hour postprandial glucose (p=0.001), but we’re certainly familiar with this perspective that Fiasp offers marginal rather than disruptive improvements over earlier mealtime insulins. We continue to believe that Fiasp represents an important option for type 1 and type 2 diabetes patients (even incremental improvements in speed can be meaningful for people taking bolus insulin, one of the most complicated drugs in existence), we were thrilled to hear Dr. Hirsch advocate for a study of Fiasp with CGM or Medtronic’s 670G hybrid closed loop. Improved time-in-range could be the most meaningful benefit of Fiasp over pre-existing rapid-acting analogs, and this has yet to be documented. Like Dr. Hirsch, we too can’t wait for these clinical trials to be done.
In a practical session on DKA management, Emory’s Dr. Guillermo Umpierrez expressed less concern over the use of SGLT-2s in type 1 diabetes than we’ve previously heard from him, which parallels the overall shift in commentary that we noticed in 2017. Dr. Umpierrez seemed particularly reassured by DEPICT 1 results, which did not demonstrate an increased risk of DKA with dapagliflozin (AZ’s Farxiga) vs. placebo. In the study, dapagliflozin also offered additional A1c-lowering, promoted weight loss, and showed an impressive benefit on time-in-range (two-three extra hours in range vs. placebo). Dr. Umpierrez acknowledged that these benefits outweigh DKA risk overall, and indeed, we’ve picked up on growing consensus in the field on this point. We very much agree with Dr. Umpierrez that SGLT-2 inhibitors should be used with great care in type 1 diabetes, and that DKA risk can be minimized with patient education and resources; this applies to Sanofi/Lexicon’s SGLT-1/2 dual inhibitor sotagliflozin as well (remarkable time-in-range benefits that outweigh DKA risk). We were happy to hear this assessment of DEPICT 1 from Dr. Umpierrez; he’s certainly an expert on inpatient management of diabetes and its complications, and we take this as an encouraging sign for the future of SGLT inhibitors in type 1 diabetes. Dr. Umpierrez referenced much of the same data he has in the past, including phase 2 data on canagliflozin (J&J’s Invokana) in type 1 diabetes that showed a small but concerning increase in DKA. He additionally mentioned case reports of euglycemic DKA from Drs. Anne Peters and John Buse published in Diabetes Care. That said, he noted that DEPICT 1 (n=833) found no imbalance in DKA between the dapagliflozin and placebo groups. Our understanding is that this was largely due to a study protocol limiting insulin dose reduction to 20% of total daily dose (in phase 2, larger dose reductions were associated with higher frequency of DKA). DEPICT 1 participants were also given glucose/ketone meters and were instructed on how to check beta-hydroxybuyrate at signs of illness, independent of SMBG results. This is very important, as Dr. Buse has articulated how absence of hyperglycemia makes it harder for patient/provider to identify – and then swiftly treat – DKA in the euglycemic condition. Dr. Umpierrez thinks this term is a misnomer – “euglycemic DKA” is technically anything under 250 mg/dl, though he has seen patients in DKA at 180 mg/dl. It’s worth noting a recent response in NEJM by Dr. Satish Garg and Lexicon’s Dr. Paul Strumph, in which they show that DKA would have been more frequent in DEPICT 1 had investigators counted “possible” instances as well; as it were, only “definite” events were positively adjudicated. Our main takeaway from this NEJM response is that differences in study design across the DEPICT and inTandem (for sotagliflozin) programs make cross-trial comparisons impossible, and above all, we think both these agents could be valuable adjunct treatments for people with type 1. With both dapagliflozin and sotagliflozin, we believe DKA risk should be manageable in the real world. As off-label use of SGLT-2 inhibitors in type 1 diabetes has become more common, and as more trials in this area have initiated and reported, the field certainly seems to have gained critical know-how on avoiding DKA with these agents, resulting in more favorable risk/benefit profiles in phase 3. Indeed, we don’t think canagliflozin inherently causes more DKA than dapagliflozin, though Dr. Umpierrez did suggest this possibility; rather, as Dr. Robert Henry pointed out in presenting those phase 2 canagliflozin results in type 1, more extensive education was likely necessary to minimize DKA risk.
- Of note, AZ recently filed dapagliflozin for type 1 diabetes with EMA (decision expected 1Q19), and Sanofi/Lexicon are expected to file sotagliflozin with FDA/EMA by the end of this month (March 2018). Finally, Lilly’s phase 3 EASE 2 and EASE 3 trials of empagliflozin in type 1 diabetes should read out this year, and we’re quite eager to see those results. To our knowledge, J&J isn’t currently pursuing phase 3 studies of canagliflozin in type 1; we suspect the company may be waiting to see how regulators respond, and might also be waiting for Invokana’s sales in type 2 to return to growth.
- Dr. Umpierrez presented T1D Exchange data showing low rates of ketone monitoring among people with type 1 diabetes in the real world – this reinforces data from dQ&A from a couple of years ago. He highlighted the urgent need for improved patient education on how and when to test for DKA. These data indicate poor adherence to ketone testing when patients are experiencing nausea or vomiting: While ketone testing practices are good for those <6 years-old (68% always test – or rather, their parents do), the numbers get worse with age. Only 23% of those 18-26 years-old always check (an equal number never do). A striking 54% and 62% of those 26-50 and >50 years-old never check their ketones in the midst of nausea/vomiting. Admittedly (and unfortunately), these numbers don’t really surprise us, but they do show that most people with type 1 diabetes just don’t test regularly for ketones. This will be such an incredibly important part of patient education if/when SGLT-2 inhibitors become an approved adjunct therapy for type 1 diabetes. In fact, since so many type 1s are already taking these drugs off-label, this education is past due – we’re hopeful that manufacturers can collaborate and lead the charge for stronger patient education on this front, which will make adjunct SGLT-2 use safer all around. Moreover, access to and coverage of ketone meters could be a big hurdle. Our impression is that most patients haven’t used anything beyond urine ketone strips, and even those probably aren’t as common as they should be.
- While the pathogenesis of SGLT-2 inhibitor-induced DKA is not very well understood, Dr. Umpierrez reviewed the dominant hypothesis. He explained that decreases in insulin dose and transient (i.e. normalizing after a few months) increases in glucagon can lead to increased hepatic ketogenesis. Alternatively, the mechanism that increases glucosuria also decreases sodium reabsorption, which can lead to increased ketone body reabsorption. More generally, he identified (i) insulin deficiency and (ii) counter-regulatory hormones (glucagon, cortisol, catecholamines) as the two typical, fundamental causes of DKA; we have heard that not having enough insulin on board to meet physiological needs (beyond just blood glucose regulation) is a major risk factor for DKA with SGLT inhibitors. Moreover, Dr. John Buse has suggested that those on low-carb diets or who are taking <40 insulin units/day may not be good candidates for SGLT-2 inhibitors. From these fundamental mechanisms arise secondary, exacerbating effects – for example, dehydration inhibits ability to flush glucose from the kidneys, causing increased hyperglycemia. Beyond newly-diagnosed diabetes, a lack of adherence to insulin and infection are typically precipitating causes of DKA. Events like alcohol use, endurance exercise, and stress have also been associated with DKA in people with type 1 diabetes on SGLT-2 inhibitors. Making sure patients know about these “precipitating events” will be another vital aspect of risk management. Euglycemic DKA is another hurdle for education: Patients need to know that they can have dangerously high ketone levels even at a blood glucose that would typically seem normal.
4. Dr. Greenbaum Shares Hope for Future of Disease-Modifying Immune Therapies in Type 1 Diabetes
TrialNet Chair Dr. Carla Greenbaum spoke to an impending paradigm shift in type 1 diabetes care, from treating the symptoms to addressing the underlying pathophysiology. She described how management of type 1 has largely focused on controlling symptoms – since the discovery of insulin in 1922, there have been meaningful improvements in insulin analogs, insulin delivery, and glucose monitoring technology, and yet the core approach to treatment hasn’t changed. That said, Dr. Greenbaum expressed confidence that we’re nearing this transition toward truly disease-modifying drugs. Several immunotherapies have shown efficacy in type 1 diabetes (Dr. Greenbaum listed teplizumab, rituximab, and the rheumatoid arthritis drug abatacept, among others). Moreover, a host of TrialNet studies are ongoing to investigate various immunotherapies to sustain insulin secretion over the long term in people at different stages of disease (pre-symptomatic, newly-diagnosed, longstanding, etc.). Dr. Greenbaum called for a change in endocrine education and training to embrace the notion of immunotherapy in diabetes, as many endocrine fellows today are not adequately trained in immunology. To underscore this point, she remarked that of the 80+ autoimmune disorders, the only four that are not currently treated with immunotherapy are the four that are managed by endocrinologists. When many fellows in the audience expressed hesitation about the clinical complexity of immune therapies, Dr. Greenbaum suggested that this actually pales in comparison to insulin – which is, after all, a lethal drug! In anticipation of a changing paradigm in type 1 diabetes management, she advised fellows to review “immunology 101,” spend time with colleagues in rheumatology (which has firmly embraced the use of immune therapies), and gain direct clinical experience in using immunotherapies in type 1 diabetes by engaging with ongoing clinical trials.
- Dr. Greenbaum outlined lingering questions on the cause of type 1 diabetes, but ultimately emphasized that “it doesn’t matter!” for clinical care, though better understanding the pathophysiology will be important in advancing novel type 1 therapies. In the vast majority of cases, she pointed out, clinicians don’t understand the true cause of the condition they’re treating (unless, she quipped, it’s a broken leg). Regardless of how type 1 diabetes is initiated, it’s clear that the disease runs in families, and Dr. Greenbaum emphasized that endocrinologists have a responsibility to educate patients and their families about the ~15-fold increase in risk for those with a primary or secondary relative who has type 1 diabetes. What are some of the lingering questions on pathogenesis? Dr. Greenbaum explained that the relative contributions of beta cell homicide (i.e. an autoimmune response that targets the beta cell) vs. beta cell suicide (i.e. intrinsic properties of the beta cell that cause dysfunction) remain unclear. Furthermore, as type 1 diabetes incidence continues to climb 3%-5% each year, it’s unclear what environmental factors are driving this and how.
- In the ensuing Q&A discussion, Dr. Irl Hirsch mentioned the possibility of GLP-1 agonists as a disease-modifying therapy for type 1 diabetes. He drew from experience with a patient in his clinic who has maintained near-normal levels of endogenous insulin secretion for the past six years using a combination of low-dose basal insulin and liraglutide (Novo Nordisk’s Victoza). While we’re intrigued by the prospect of yet another application for GLP-1 agonists (in addition to type 2 diabetes, obesity, and maybe Alzheimer’s), we note that Novo Nordisk opted not to pursue a type 1 indication for Victoza in 2015, based on variable efficacy in different patients in the phase 3 ADJUNCT program (we question whether the optimal doses were used). Perhaps interest in a type 1 indication will resurface following positive data from the Lira Pump Trial (presented at ADA 2017), in which liraglutide significantly increased time-in range vs. placebo. But we’re not holding our breath in the near term. Dr. Greenbaum was quick to point out that an ongoing study (sponsored by Novo Nordisk) investigating liraglutide in new-onset type 1 diabetes is expected to complete in the next one-two years. The trial is evaluating preservation of beta cell function. She underscored that prior studies of GLP-1s for type 1 were conducted in patients with longer duration of disease at baseline.
Diabetes Technology Highlights
1. Dr. Umpierrez Advocates for RCTs Investigating Technology Use in the Hospital Setting; Sees “Limited Future” for CGM Use in the ICU
Emory’s Dr. Guillermo Umpierrez called for randomized controlled trials investigating pump and CGM use in the hospital setting, characterizing this area as an “open field.” In fact, even the prevalence of hypoglycemia in hospitalized type 1 diabetes patients is unknown – a “simple project” for a type 1 diabetes fellow to take on. While data in this sector may be limited, the population at stake is far from it: there are 7.2 million patients with diabetes discharged from hospitals in the US every year, comprising 23% of all hospital discharges. Diabetes contributes to 14.2 million emergency room visits per year accounting for $124 billion in healthcare expenditure in 2012. While Dr. Umpierrez touched on both pumps and CGM in his presentation, he highlighted a particular need for improved insulin control in the hospital setting. According to Dr. Umpierrez, insulin use is among the top five medications associated with medication errors in the hospital – a sobering, but not all that surprising statistic. We continue to hope CGM expands to keep patients out of the hospital, but if they do end up there, that real-time sensors can inform safer dosing and more time-in-range. Read on for Dr. Umpierrez’s cautiously optimistic perspective below.
- As for CGMs, Dr. Umpierrez believes “the future of CGM in the ICU is very limited” but has a bit more faith in the potential of non-ICU CGM use in the hospital setting. He emphasized the need to learn more – as he pointed out, how might sensor compression from bed-bound patients affect accuracy? Although he acknowledged the OptiScanner, the first inpatient CGM cleared by the FDA for surgical intensive care unit (SICU) use, he cited a recent systematic review showing no improvement in outcomes with ICU CGM use as compared to hourly fingersticks. As he argued, “Why buy the OptiScanner if you can prick patients’ fingers every hour?” We’d point out that reducing the need for hourly fingersticks would significantly reduce nurse burden, not to mention patient pain. Indeed, Dr. Umpierrez acknowledged these advantages when describing the FreeStyle Libre for non-ICU use, citing the lack of fingersticks as beneficial for nurses. Dr. Umpierrez noted that in the non-ICU setting, CGM has been shown to improve hypoglycemia and hyperglycemia recognition, but not overall patient outcomes. He acknowledged that CGM has been proven to be safe in the hospital, adding that more research is needed to determine which patients will benefit the most. He expressed enthusiasm regarding implantable CGMs, characterizing Eversense as “very cool,” but stipulated that there currently lacks data supporting its use in the hospital. Dr. Umpierrez incorrectly stated that Eversense is FDA approved, when in fact an FDA Advisory Committee meeting to review its PMA submission is scheduled for March 29.
- Dr. Umpierrez briefly mentioned a pilot study investigating the Glucose Telemetry System, claiming “this is the future.” The paper, recently published in the Journal of Diabetes Science Technology, lists Dr. Umpierrez as an author and includes data from five type 2 patients in the general hospital wards whose Dexcom CGM values were transmitted to a central nursing station monitoring system. CGM alarms were set up for glucose readings <85 mg/dl. Over the four days of CGM observation, patients spent 65% of the time in-range (“70-179 mg/dl”) and only 0.3% of the time <70 mg/dl. No patients had a CGM glucose value <54 mg/dl. This is terrific data and far better than type 2s generally do in the general ward. We’ll be excited to see CGM move into the hospital setting and we hope to see at least one of the players move forward on this. Who will be brave enough to do it? Dexcom’s G6 was long-ago positioned for use in the hospital, but we haven’t heard an update in a long while.
- When it comes to continuing pump therapy in the hospital, Dr. Umpierrez emphasized careful patient selection. The bottom line, according to Dr. Umpierez, is that pumps have been shown to be as safe and effective as MDI in hospitals, but that one third of patients on pumps reveal knowledge deficits upon arriving to the hospital, underscoring the importance of assessing patient education. While retrospective studies have shown that most patients can safely transition pump therapy to inpatient use, randomized controlled trials haven’t happened. Current hospital guidelines recommend continuous variable insulin infusion for ICU patients and either subcutaneous pump or MDI in non-ICU patients. Dr. Umpierrez proposed contraindications for continuing pump use in the hospital including: (i) impaired patient level of consciousness; (ii) inability of the patient to correctly demonstrate appropriate settings; (iii) any interference with patient self-management; and (iv) lack of sufficient administrative support and/or trained healthcare professionals. If any of these conditions are met, Dr. Umpierrez recommends putting patients on a “pump vacation;” however, he noted that there is a lack of supporting evidence and a clear need for randomized controlled trials comparing pumps vs. pump holiday regimens.
- Dr. Umpierrez lamented the recent reduction of pump options in the US, mentioning the Animas exit. He also surprisingly cited rumors that Tandem is not on the market anymore; obviously given its strong 4Q17 results, 17,061 pumps shipped in 2017, and enough cash to reach breakeven (expected in 2H19), this is not the case. Still, it’s a sign of what respected HCPs are hearing about Tandem, something the company will need to address in the coming months as it prepares for PLGS to launch this summer (currently under FDA review).
2. Stricter Medicare Pump Guidelines Requiring 2 Months of Fingerstick Data Initiate in April; Visual Impairment Adaptations Lacking in Pumps/CGM
In a breakout session on pumps led by Dr. Janet McGill (Washington University in St. Louis) the message was clear: determining the right pump for the right patient is a central part of a physician’s role, as is understanding the various CGM and pump integrations and reimbursement structures. We were disappointed to hear that Medicare guidelines for pumps are “getting more stringent” come April 1. Providers must now document four fingersticks/day for two months prior to initiating a new pump or upgrade; in the future, Dr. McGill believes the same strict testing and documentation requirements may even be applied to ordering supplies. To this end, she emphasized the importance of detailed documentation, highlighting that the transition to Medicare can be a major patient satisfaction problem if coverage for pump, CGM or supplies is not attained. Dr. Irl Hirsch described, to horrified gasps from the audience, how Medicare once rounded down 3.8 fingersticks/day to 3 fingersticks, denying a patient coverage. As Dr. McGill noted: “this is going to be painful.” Dr. McGill also provided a valuable overview of the various pumps on the market, claiming that she finds the Omnipod patch pump particularly useful for children or visually impaired patients with a readily available seeing spouse. Visual impairment came up several times throughout the talk – Dr. McGill emphasized that adaptations for the visually impaired are “really lacking” in pumps and CGM devices in general. At least for pens, patients can use the clicks as an auditory guide. Dr. McGill also mentioned V-Go, Valeritas’s 24-hour basal-bolus patch insulin delivery device, as a strong option for patients who are uncertain about initiating pump therapy for a variety of reasons. As expected, she characterized V-Go as more useful in type 2 rather than type 1, though she has some type 1 patients using it successfully. Dr. McGill nicely summarized the discussion by referencing the multiple hats worn by diabetes healthcare professionals, including that of the occupational therapist, psychologist, financial counselor, and support person. As technology continues to advance, more work will certainly be demanded of both patients and providers, with the ultimate goal of reducing both patient and provider burden and improving outcomes.
- Dr. McGill highlighted that despite many success stories of patients on the Medtronic MiniMed 670G, the hybrid closed loop system can also be a major source of frustration and confusion for those constantly getting kicked out of auto-mode. She advised providers to review basic diabetes management skills like carb counting and blousing before meals prior to starting patients on the 670G. She also cited <50% of time in auto-mode and requests for frequent calibrations as a red flag for uncertain diabetes management habits. Dr. Hirsch chimed in, mentioning that teaching patients “carb lying” is especially important for the 670G – in other words, falsely informing the 670G that carbs are going to be eaten to account for up arrows on the Guardian CGM. (This is actually a great reminder for Medtronic and the FDA that making a system so conservative that patients cheat it also carries risk.) Echoing others, Dr. McGill highlighted that overnight time-in-range is improved in almost every patient on 670G.
- Surprisingly, Dr McGill expects a “fully closed loop” system within five years. This timing seems ambitious to us, unless she characterizes a system with automatic correction boluses (e.g., Tandem/TypeZero/Dexcom) as “fully closed loop.” Even still, it won’t be “fully closed loop” unless someone is eating pretty low-carb.
Big Picture Highlights
In an opening keynote address, “Cheating Destiny,” author Mr. Jim Hirsch (brother to conference organizer Dr. Irl Hirsch) reminded endocrine fellows of the highs and lows (literal and figurative) of living with diabetes – “all of your failures are public and all your successes are private.” Mr. Hirsch told the story of his own 1977 diagnosis with type 1 diabetes, at a time when accurate home BGM was just becoming a reality. He referenced a CBS evening news story by Walter Cronkite around that time, in which the anchor presented this statistic: If you have diabetes, you have a 50/50 chance of reaching age 40. Mr. Hirsch knew his chances were better, however. For one, he had access to good care (unfortunately, so many patients even today lack access to high-quality medical care, and cost of care still determines outcomes in diabetes multiple decades later. He also explained that he was lucky to have diabetes at a time when insulin therapy was available. While science and technology have brought diabetes care quite far since the 70s, the impact of type 1 diabetes on individuals and families remains significant – and this is an important message for endo fellows to hear. Indeed, for Mr. Hirsch, ~40 years of living with type 1 diabetes seems to pale in comparison to his son’s diagnosis with type 1 at age three (Garrett is now a junior in high school). With this diagnosis, and with Garrett saying “I have diabetes” for the first time, Mr. Hirsch thought his son’s childhood was over. He enumerated challenges that Garrett and his family have faced: Garrett liked to eat carbs but not really vegetables or protein, and he hated insulin injections. The family met these challenges with solutions: They’d run wind sprints or play games to keep blood glucose down after dinner, and Garrett would get to pick where he received his injections. When Garrett was in third grade, a man who used a wheelchair visited his school during National Disability Month, and Garrett asked the school nurse if he himself was disabled. Through a series of stories like this, anecdotes about Garrett that seemed to diverge from popular notions of “childhood,” Mr. Hirsch highlighted a key theme about the patient experience with type 1 diabetes, particularly for youth. As Mr. Hirsch put it, diabetes isn’t a chronic disease to a kid or teenager – diabetes happens when it intervenes in your life. Thus, he tried to minimize the extent to which diabetes intervened in Garrett’s life – a goal requiring equal parts ingenuity, persistence, and teamwork. Mr. Hirsch described his approach as thinking about what diabetes doesn’t allow you to do, and then finding a way to do it. When things go well, Mr. Hirsch said, you have to know to take credit, but when you have a bad day, you also need to know to blame the disease and resolve to do better tomorrow. On the importance of person-first, non-stigmatizing language, Mr. Hirsch spoke out against the idea that diabetes makes you “unhealthy” or “diseased.” He mentioned the recent ADA/AADE position statement, published in Diabetes Care and The Diabetes Educator in October 2017. In his final story of the night, Mr. Hirsch shared a comment that Garrett made about not knowing whether he would want a type 1 cure if one was developed. “I’ve heard teenagers with type 1 diabetes say that it made them more resilient, self-sufficient, or a better person,” Mr. Hirsch explained. “I don’t think Garrett was saying that: I think he was saying it made him who he is today, and he was okay with that.” Always a great speaker, Mr. Hirsch set the perfect tone for the rest of Endo Fellows, reminding healthcare providers that people with diabetes exist almost entirely outside of the clinic, and that diabetes has to be approached as just one component of an individual’s full life.
During an emotional dinner symposium, Dr. Robert Eckel and his wife Margaret, alongside their son Clark and daughter-in-law Jami, discussed their family’s journey with type 1 diabetes – this session is an annual favorite of the Endo Fellows agenda, and this year’s panel certainly did not disappoint. Dr. Eckel has had type 1 diabetes for 65 years. He is a former president of the American Heart Association (AHA) and is a leading diabetes and cardiology expert, focusing on lipid and lipoprotein research. He and Margaret have raised five children, two of whom, Peter and Clark, also have type 1 diabetes and were diagnosed as teenagers within one month of each other. Both Peter and Clark are professional cyclists for Team Novo Nordisk; being athletes has been a key piece of their diabetes stories. The hour-long conversation offered several useful tips and tricks on type 1 diabetes management, though the dinner as a whole is perhaps best captured by this quote from Clark: “At the end of the day, I’m a patient and my body is my own. To convince a patient to change, you have to get them to truly believe for themselves that what you’re suggesting is the best option.” In our view, this is excellent advice for endo fellows and others who treat diabetes, and it reinforces that patients have to be engaged in shared decision-making. Margaret’s only exposure to diabetes before marrying Dr. Eckel was her cat with diabetes. She shared that rubbing honey, syrup, or molasses on an individual’s gums can be incredibly effective during severe hypoglycemia. This hack came into play for Margaret during a particularly challenging night when Clark was having a seizure. To make matters even more complicated, both Dr. Eckel and Peter were very low themselves, but were still trying to help Clark. There was no glucagon in the house. Margaret recounted the evening in vivid detail, describing how Peter attempted to get Clark to drink Gatorade, ultimately dumping the drink all over Clark’s bed. Eventually, Margaret was able to use the honey trick on Clark; it worked within 10 minutes, at least as a temporary fix, until he could also engage. Then, Peter and Dr. Eckel accepted Gatorade themselves and recovered from their hypoglycemia. This story served as a reminder of the massive responsibility incurred by caregivers of those with diabetes, not to mention the degree of spontaneity and creative thinking demanded. As Dr. Eckel put it, “Margaret has been to the medical school of experience.” Jami acknowledged that diabetes is certainly a stressor on her marriage with Clark, requiring strength on her part to deal with the pressure of making critical judgment calls. Family support was a major theme throughout the discussion, with Clark referencing an intervention by his father, Margaret, and Jami to encourage his transition to CGM. Even before that, Margaret and Dr. Eckel took an active approach in shaping Clark’s and Peter’s perspective regarding their diagnosis. Margaret described at length how she wanted to avoid fostering an environment of fear; instead, soon after Clark and Peter were diagnosed, the entire family went on a week-long camping trip to demonstrate that if certain precautions are taken, diabetes should not interfere with the activities and experiences they enjoy. As Dr. Eckel stated, “I don’t call type 1 diabetes a disease. I call it a life.” Still, Margaret was careful to acknowledge Dr. Eckel’s expertise, which made their family’s experience with diabetes different from that of many others. To help instill the same mentality in patients who don’t have a renowned endocrinologist in the family, she and Clark urged providers in the room to encourage their pediatric patients to attend diabetes camps. See our detailed discussion and commentary section below for a full transcript of this event.
- More than anything, Clark emphasized the importance of providers building strong relationships with their patients, even prioritizing this connection over actual medical advice. He noted that a meaningful relationship is particularly crucial during adolescence and transition to adult care. During his own journey toward beginning CGM, he cited the reduced fingersticks and trend arrows as particularly enticing. In an important reminder of the limitations of A1c, Clark had a very low A1c of 6.5% prior to CGM, all while experiencing a total of seven seizures. Now on CGM, his diabetes “has never been the same since,” improving substantially despite his A1c being a little higher.
- Dr. Irl Hirsch (who moderated) proposed two future diabetes studies resulting from the conversation. In response to Clark’s positive experience taking Afrezza (MannKind), NovoLog (Novo Nordisk), and Tresiba (Novo Nordisk) as an athlete, Dr. Hirsch noted a lack of studies evaluating intermediary metabolites in athletes who take Afrezza. As he acknowledged, most diabetes studies just measure glucose, when in fact the reality is “much more complicated than that.” Following one question referencing the limited time providers have with their patients, Dr. Hirsch called for a study investigating an association between time spent with patients and outcomes. He noted an informal survey he conducted with 200 endocrinologists in Seattle – two-thirds reported spending 20 minutes or less with their patients, a finding he described as “very alarming.”
Detailed Discussion and Commentary
Patient Engagement Panel: Full Transcript
Irl Hirsch, MD (University of Washington, Seattle, WA); Robert Eckel, MD (University of Colorado, Aurora, CO); Margaret Eckel; Clark Eckel; Jami Eckel
Dr. Irl Hirsch: A lot of people in the audience have type 1 diabetes, or have a family member or spouse who does (I’ve heard a lot of names for this, including “type 3 diabetes”). If you have a close family member or especially a spouse with diabetes, you know things we can’t teach you from PowerPoint presentations, but this session is intended to give a window into the patient experience. To begin, why don’t you all introduce yourselves.
Dr. Robert Eckel: I developed type 1 diabetes when I was five, and I have no memory of life before diagnosis. I’ve now had diabetes for 65 years, and I’ve never felt better in my life than I do now.
I grew up in Cincinnati, went to high school and college there, and ultimately went on to medical school. I came from a single mother household, and my older brother and basically served as a father figure to me. I decided to specialize in internal medicine because my mother wanted me to be like my late father, a PCP, who came back from World War II and died shortly after of colon cancer at age 35. I went to University of Wisconsin for training, but I felt there was more to life than internal medicine, so I next went to Seattle because of the program’s emphasis on diabetes alongside CV disease and nutrition. I had a tremendous training experience there, and eventually landed in Colorado 39 years ago. Colorado is a tough place to leave, and we’ve been there ever since.
I met my first wife, Clark’s mother, in junior high. She died in 1994 of breast cancer, and all of a sudden I was a single father to five children. Margaret was dating a friend of mine – I actually attended her wedding with my first wife! They eventually divorced, and after my wife passed away we started hanging out. She was willing to marry a guy with five kids.
At this point in my career I do a lot of basic science, mostly in lipids and lipoproteins in the context of multiple sclerosis and Alzheimer’s disease. My clinical work is in cardiology and I deal with preventive cardiology from a metabolic perspective.
Dr. Hirsch: I’ll just say that I’ve known Bob for years. We were once on the Board of Internal Medicine together; he was in charge of lipid questions and I was responsible for diabetes questions. We became allies because we were always defending the issues in diabetes.
Ms. Margaret Eckel (Dr. Eckel’s wife): Bob and I married in 1995, and within two months of that Clark and his brother Peter, who is 18 months older, were both diagnosed with type 1 diabetes. Many years ago I had a diabetic cat, so I had some experience. When Bob and I were dating I’d say “you’re low” and he’d say “how do you know?”. Well, my cat couldn’t tell me when he was low and I had to learn his body language; it turns out that Bob had the same body language – the same tilt of the head, everything. He never could believe I could recognize it so well. Anyway, Bob was my initial experience with type 1 diabetes in humans, but once our two boys were diagnosed we ended up spending a lot of time at the Barbara Davis Center.
Mr. Clark Eckel (Dr. Eckel’s son): I’m the youngest of five, and I was diagnosed with type 1 diabetes at age 11. That was an interesting part of my life – trying to fit in during middle school but having just lost my mom to cancer and getting used to a new stepmom. I was in a unique situation having my dad as both an endocrinologist and a person with type 1 diabetes himself – I had a bit more coaching than most kids.
Going through high school I wasn’t as preoccupied by fitting in and learned to see diabetes as part of my life. I started riding bikes at age 14 and later went pro. I returned to college at age 26, and now I’m 34 and own my own business. In the last few years I’ve been racing again professionally as part of an all-T1D cycling team. My wife Jami and I live in Denver. Diabetes taught me a lot of life lessons… It’s been my life, and not a horrible one at that – especially with the right coaching and help.
Ms. Jami Eckel (Clark Eckel’s wife): I’m just a normal person that happened to marry into this family – without previously having any friends or relatives (or a cat) with diabetes. It’s been a 10 year journey getting to know the disease and how it impacts Clark’s life and mine.
Dr. Eckel: Let me make sure the audience understands that both Irl and his brother Jim have type 1 diabetes. I’ve encouraged Irl for years that he should let me interview his family next year!
Dr. Hirsch: I want to start with Margaret, since spouses often have the most interesting and colorful stories to share! So, Margaret, if you go back and think of all of the different experiences you and your family have had together with diabetes, what stands out the most as something the fellows should hear?
Margaret: As I mentioned before, both boys were diagnosed with type 1 diabetes within two months me marrying Bob, in October and November of 1995. Bob and I felt it was important to show the boys that the fact they have diabetes doesn’t preclude them from skiing, biking, spending the night out, or otherwise just being normal kids. I saw a lot of terrified parents in the waiting room of the Barbara Davis Center, and we were from a different mindset because of Bob’s experience managing his diabetes. We didn’t want any limitations for our boys. So we planned a major backpacking trip for the summer of 1996, carrying all our own food and water, in order to show the boys that if they were prepared they’d be able to do anything. After a week in the backcountry, they realized that they don’t have to be afraid of diabetes.
The boys were comfortable taking their own injections from the very beginning because they grew up watching their dad. At Barbara Davis Center they’d ask Clark to show them how he takes a shot: He’d inject right through his shirt and they’d say “oh no, that’s not correct!” and he’d say “but that’s how my dad does it.” The nurses were terrified. They’d also ask “how long until you change a needle?” and Clark would tell them “oh, until it bends.”
Dr. Eckel: When I was a fellow in the 1970’s a paper came out showing that injecting through clothing is just fine.
Dr. Hirsch: Note that this is not on the FDA label!
Margaret: There was one time within a year or two after the boys’ diagnoses that we had a pretty bad experience at home, and this is the kind of thing your patients will experience too.
One night I was awakened by a wailing noise that sounded like a mountain lion outside in the woods. But it kept going on and on so I got up and wandered around the house to find out what was happening. I finally end up near the boys’ bedrooms. I open Clark’s door and he’s having a severe low – he’s seizing and the wailing noise is coming from him. Because Clark is seizing I can’t give him anything to drink, and we didn’t have any glucagon in the house. So I wake up his brother Peter, but Peter is just as low as Clark but still coherent. Peter tries to help Clark and is pouring Gatorade all over him and all over the bed – he couldn’t understand what was happening.
I run upstairs to get Bob, but he’s also low! Both Bob and Peter are trying to help me with Clark but they’re so low they can’t function at all. I couldn’t do anything to help Clark until I could get Bob and Peter to leave him alone, so I got them something to drink. Then for Clark I put honey on his gums. It’s like glucagon and will work within 10 minutes for someone’s who’s seizing if you can get it in without the person biting off your finger!
So Bob and Peter with Gatorade and Clark with honey. I was like a maniac running up and down the stairs between them. I could have called 911 but to be honest I was too occupied to even try to call at the moment.
Q: How did you think to use honey?
Margaret: My cat! I learned with him that honey or molasses or syrup on the gums works very quickly. I’ve done it before with Bob on another occasion.
Dr. Eckel: To be clear, we do have glucagon now!
Margaret: We have glucagon, and you know a lot of people get it and then don’t use it because they’re nervous that it will go bad. Now I’ve been doing this for 20 years: I premix it, write the date on the vial, and leave it unrefrigerated. Yes, in a few months it’s maybe not as efficacious in premixed and unrefrigerated form, but it works! I usually just administer 10 units of glucagon, let Bob’s blood sugar rise to the point that he’s able to communicate, and then give him something to drink. If you give an entire glucagon dose the person will begin to vomit and it’s not an ideal situation.
Dr. Eckel: Margaret has been to the medical school of experience! Keep in mind that glucagon does work in much lower doses than you’d expect. I’m not endorsing what she says about living it premixed and unrefrigerated, but it does still work to some degree under those conditions.
Dr. Hirsch: There are a lot of pediatric endocrinologists in the audience, dealing with kids transitioning to the adult side of diabetes management. Clark, thinking back to this point in your life, how did this go with your physicians and what advice would you give these doctors in training?
Clark: When I growing up and evolving through high school, diabetes was something I hid from people and was embarrassed by. That’s something any teenager probably goes through. But as a mature adult you don’t really care anymore, and diabetes becomes just a part of what you do. The structured environment and support you have at home and in doctor’s office is so vital, and that relationship you build with the endocrinologist is more applicable than anything else. I’d say that the relationship you build is more important than medical advice you give.
Dr. Hirsch: Your endocrinologist might know that you’d do so much better with an insulin pump or with CGM, but you say you don’t want to go there. So from the patient perspective, how should we physicians react when you push back against advice?
Clark: That’s a loaded question! At the end of the day, I’m a patient and my body is my own. If I decide to ride a bike and quit taking insulin, that’s my choice and you can’t stop me. To convince a patient to change, you have to get them to truly believe for themselves that what you’re suggesting is the best option.
Priorities change as you grow. At the end of the day, diabetes comes into view as a major thing you focus on throughout the day. Certain things are more enticing to help with diabetes management, and CGM was that for me. In my opinion it’s more important than a pump – after all you dose insulin depending on glucose level and not the other way around.
I started CGM about seven years ago. I was training a lot and my diet was pretty light because I was trying to lose weight. I was still on the same insulin regimen and started having frequent severe hypos and seizures. I’ve had seven in total, and besides the one Margaret mentioned, all have been post 21 years of age. After the fourth seizure, everyone realized something needed to change – these are near-death experiences. After my second ambulance ride, something had to change. Dad, Margaret, and Jami took me to my endocrinologist and we decided to get me on a CGM. My diabetes hasn’t been the same since.
My A1c has always been really low, which signals to the physician that management is good. But behind that 6.5% A1c is a lot of frequent lows.
Dr. Hirsch: What do you do now for diabetes management?
Clark: I’m on CGM and take insulin injections. I’ve always strayed away from the pump because I’m really clumsy and nervous that the tubing would get caught and rip out. Also, I was dating Jami and having a pump attached to me didn’t sound very attractive either. The CGM is wireless and I like that.
Dr. Hirsch: What about the Omnipod?
Clark: It was recommended to me as an option but it just sounded like too much stuff to worry about. I take NovoLog and Tresiba. I also take Afrezza sometimes; I recently went through a study comparing NovoLog and Afrezza and it was phenomenal. As an athlete Afrezza absolutely changed the way I manage my diabetes. I race short events at 30mph; it’s an insane environment, talk about adrenaline! As you exercise you lose strength and dump glucose. The Afrezza really affects way you ride because takes away the peak glucose regardless of what I’m eating. I’d see an effect in 12 minutes according to my CGM. Using all three insulins is the best for me.
If you have an opportunity to work with your patients in a practical way, it’s so helpful to apply these different techniques so they find what’s best for them at a personal level. We’re all different, and even for one person things are different from day to day.
Dr. Hirsch: I hadn’t thought about that until just now – looking at intermediary metabolites in athletes who take Afrezza! We just measure glucose but obviously much more complicated than that. Jami, what did you marry into? Did you have any idea what this would be like?
Jami: For the longest time, Clarke actually hid his diabetes. It was an interesting dynamic when he finally told me. It’s concerning when you’re not used to needles and have no idea what it feels like to be high or low. To some degree it can put stress on the relationship, but we’ve taken the time to learn what works best. Margaret has certain tips and tricks and I’ve learned some of my own too. I’m fortunate that I’ve never had to administer glucagon!
Dr. Hirsch: I’ve had patients come to my office and we give the spouse insulin so they can feel what hypoglycemia is like. Have you ever done that?
Jami: Taking a fingerstick is the closest I’ve gotten!
Dr. Hirsch: Did this have any impact on your relationship when you were dating?
Jami: It was definitely a stressor, and I had to evaluate whether I would be strong enough to deal with it. I sometimes worry that he is going to have a seizure and die, and I’m the one who has to make the judgement call of whether to call 911. We don’t have those super crazy lows anymore, so in the last several years I have a sense of relief.
Dr. Hirsch: Clark, I assume you wear a Dexcom CGM… Do you share your data with Jami?
Clark: I do share, but that was a mistake!
Jami: We finally agreed with what the low alarm should sound like (there are some really bad ones out there!).
Dr. Eckel: Thinking back to the hypoglycemic events we’ve experienced… I don’t call type 1 diabetes a disease, I call it a life. For the six people in the audience with type 1 diabetes, you know what I’m talking about: Where’s my glucose now? Where has it been? Where is it going? How much insulin do I have on board? This requires constant management, but I’ve never complained.
I used U40 globin insulin until age 30 – this was once-daily, 18-hour, dirty insulin. And there was no fingerstick monitoring! To think, for 25 years of my diabetes I had no idea what was going on with my blood sugar. I feel so fortunate. When I was diagnosed my outlook with type 1 diabetes was gruesome. People with type 1 diabetes now are living almost normal lives in terms of longevity. In this era the prognosis is anything but grim. It’s been a life and I’m fortunate to be alive. I’m thankful every day.
Dr. Hirsch: I’m at 54 years with diabetes, and I don’t think I’ll ever catch up to you – in so many ways.
Q: Clark, since it took you a while to get CGM, was there something your endocrinologist could have said to convince you earlier?
Clark: My endocrinologist is a straight shooter, he’s all about the data. Sometimes that can be paralysis by analysis. At some point I needed him to talk less about the numbers and emphasize instead what it means for my life. In the case of CGM the message that sold me was that it was two or three finger sticks per day instead of 1o. That plus the ability to see the trends in your blood sugar and how insulin influences this. That’s especially enticing to someone who’s very active.
Q: You have this amazing support system in your family, but in terms of me managing a patient who doesn’t have that support system and I only have 20 minutes to talk to them, if I find out that they may be going through slump and need a lift, what is something that will really hit that nerve? What’s something I could say to help lift them up?
Clark: I think you’ve hit on a very interesting point. I’ve grown up in a unique family. Most patients don’t have diabetes in the family. I didn’t go to a diabetes camps because I had my father, but I really believe in diabetes camps now. It’s a clique in a different environment where you’re getting to know these kids who deal with the same disease. It’s really something to become a part of. They can relate to each other. There are a lot of resources out there but you have to look for them. As a physician, you have to really push them to look for other outlets. The 20 minutes you have with patients is not all the time they deserve. It’s essential they look for other resources. This is especially important for parents of kids with type 1 diabetes – if 20 minutes with a doctor is the only experience they have with diabetes it shuts down the opportunity of having a normal life.
Jami: Being someone who doesn’t have diabetes, trying to build comradery and engaging with patients is so helpful. Try to help your patients’ friends and family build a support system. Advise your patient that if you go to an outreach event, bring those people with you so they can lift you up. If they’re not scared of your disease because they understand it’s your life that’s key.
Dr. Eckel: I insist on having a CDE come with me. It’s important for the whole team to be on the same page. If you only have 20 minutes, the CDE may have 25 or 30.
Dr. Hirsch: In every community there are resources and you need to know what they are. ConnecT1d.org is a great online resource in Seattle. When I get a patient and I can tell things aren’t going right, what I like to do is bring in a family member, usually a spouse or significant other, because that person knows more about everything else going on in the patient’s life that impacts diabetes. It has served me so well. Just meeting them gives my patients and me a place to talk. Patients can appreciate that. I did an informal survey and it was very alarming. Among 200 private practice endos, two thirds of them get 20 minutes or less for patient interaction whether it’s Hashimoto’s or type 1 diabetes. The system is what it is, but I actually think that if someone would do a study, how much time physicians spend with their patients and the associated outcomes would be so important. The problem with where we are now is that that part of medicine, just talking with patients, has been taken away from us. For type 1 diabetes it really matters.
Q: Dr. Eckel mentioned getting confrontational at times. We get a lot of teen patients who don’t want to be micromanaged. Do you have any advice we might give to their parents?
Margaret: When Bob is confrontational it’s when he’s severely low, same with Clark. Clark and Peter grew up seeing their father managing his diabetes every day, so when they were diagnosed from day one they were pretty much managing their diabetes because they thought this was normal. The confrontation we experience is when they’re having severe lows. I’ve learned I have to not get upset or raise my voice during those times. I have to be calm and try to convince them to get something to drink. Sometimes it’s not simple.
Dr. Eckel: Margaret’s feline experience is useful. She noticed the pupillary response when her cat would go low and it’s the same with me. She’s right nine out of 10 times and sometimes I’ll go to my mirror and look at my eyes and check.
Jami: Our confrontation is when they’re low, and in that situation it’s important to educate parents on allowing teens to be responsible for themselves. If parents are so afraid and consumed, you’re always going to have that confrontation. You have to convince the parents to allow their children to be responsible for themselves. Maybe you use a sharing app so that you can come intervene for emergencies, but you have to build children up to be able to deal with diabetes themselves.
Margaret: We’ve been very fortunate because we hike and ski and we encouraged the boys to do all those things and take responsibility for their diabetes. But the camps are so good not only for kids but to empower parents. They can volunteer and be part of it, but more importantly they can finally see their child is actually going to take responsibility for their diabetes. Get those kids to diabetes camp. It’s the best thing going to get them to be accountable.
-- by Ann Carracher, Abigail Dove, Payal Marathe, Maeve Serino, Adam Brown, and Kelly Close