Diabetes news

ADVANCED TECHNOLOGIES AND TREATMENTS FOR DIABETES 2019

The Advanced Technologies and Treatments for Diabetes (ATTD) 2019 meeting took place in Berlin, Germany, from February 20 to 23. There, Dr Chantal Mathieu (Katholieke Universiteit Leuven, Leuven, Belgium) reviewed available Phase 3 data on sodium-glucose cotransporter (SGLT) inhibitors in type 1 diabetes (T1D) and took a conservative stance by framing these agents as “promising adjunct therapies” while cautioning that “we have to strike the right balance between benefits and side effects”. She also underscored that SGLT inhibitors should be used carefully in T1D patients, in whom weight loss is undesirable. She presented this as a safety consideration, because preventing undesired weight loss could also decrease risk for diabetic ketoacidosis (DKA) and unpredictable glucose fluctuations, perhaps by maintaining insulin requirements.

Conference co-chair Dr Tadej Battelino (University of Ljubljana, Ljubljana, Slovenia) was critical of the European Medicines Agency's (EMA) potential new indication for SGLT-2 inhibitor dapagliflozin, which recommends use in T1D patients only if they have a body mass index (BMI) above 27 kg/m². He argued that the entire T1D population could benefit from an adjunct therapy that offers additional HbA1c lowering, improved time in range, and weight loss. Dr Battelino also outlined one hypothesis in which these drugs reduce glucose variability, thereby alleviating oxidative stress and endothelial dysfunction, which brings down cardiovascular event rates. He added explicitly that glucose variability is not correlated with obesity, so limiting dapagliflozin's use to T1D patients with a BMI above 27 kg/m² is an oversight of the most meaningful benefit SGLT inhibitors could have for T1D patients (cardiovascular risk reduction). Dr Battelino acknowledged the uncertainty around mechanisms of cardiovascular benefit, but focused attention on what is certain: “If you ask about the SGLT's cardiovascular mechanism, the honest answer is ‘we don't know’, but we do know that people with T1D are only getting worse with metabolic control and consequently CV outcomes.”

Dr Robert Ritzel (Klinikum Bogenhausen, Munich, Germany) discussed a hypothesis for the difference in hypoglycemia rates observed during the titration period of the BRIGHT study.1 The BRIGHT data (n = 929) showed that, during the 24-week study's 12-week titration period, insulin glargine U300 was associated with a 26% lower risk of hypoglycemia <70 mg/dL (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.57-0.97, P = 0.03) and a 37% lower risk of hypoglycemia <54 mg/dL (OR 0.63, 95% CI 0.40-0.99, P = 0.004) compared with insulin degludec.1 Dr Ritzel offered a possible explanation that highlights the importance of individual characteristics of each insulin: given that hourly data from the titration period show the hypoglycemia differences occurred between approximately 4 am and approximately 12 pm, Dr Ritzel hypothesized, in conjunction with published pharmacokinetic and pharmacodynamic (PD) data, that insulin degludec may have a slightly stronger effect on fasting glucose. In support of this hypothesis, he pointed out that both insulins were injected in the evening and have only small differences in their PD profiles, reasoning that the “highly dynamic” period of titration may allow each insulin to exhibit some different, inherent characteristics more readily.

NETWORK FOR PANCREATIC ORGAN DONORS WITH DIABETES 11TH ANNUAL SCIENTIFIC MEETING

The Network for Pancreatic Organ Donors (nPOD) 11th Annual Scientific Meeting took place in Hollywood, Florida, from February 19 to 22, 2019. There, Dr Mark Atkinson (University of Florida, Gainesville, Florida) provided an overview of the state of nPOD, calling the organization “the biggest T1D project in the world”. Dr Atkinson noted that nPOD now has 238 projects in 21 countries and has collected over 50 000 stored samples. In addition, nPOD has supported over 24 000 histology images that are now available online, and directly supported over 200 publications, many of which are in the highest-impact journals in the field. Dr Atkinson also remarked that nPOD has been “absolutely at the essence” of addressing many of the common shortcomings in developing preventative measures for T1D (namely suboptimal trial designs, limited interest from the pharmaceutical interest in the disease, a lack of informative biomarkers, a failure to appreciate disease heterogeneity, and others).

Dr Emily Sims (University of Indiana, Bloomington, Indiana) presented data from a recently published Diabetes Care study indicating that, in individuals with long-duration T1D, the ability to secrete proinsulin persists even in those with undetectable serum C-peptide levels.2 The study measured C-peptide and proinsulin levels in 319 subjects with T1D in both fasting and stimulated serum. Patients were binned into three categories of stimulated C-peptide levels: (a) C-peptide positive, with high stimulated values >0.2 nM; (b) C-peptide positive, with low stimulated values between 0.017 and 0.2 nM; and (c) C-peptide levels below 0.017 nM. Very notably, 96% of subjects were observed to have detectable proinsulin levels and nearly 90% of subjects without detectable C-peptide levels were found to have measurable proinsulin levels. Interestingly, fasting proinsulin levels were nearly identical across all patients, regardless of stimulated C-peptide values. Dr Sims and colleagues conclude from these data that “the vast majority of subjects with long-standing T1D retain the ability to initiate preproinsulin production and secrete proinsulin”.2

AMERICAN DIABETES ASSOCIATION 66TH ADVANCED POSTGRADUATE COURSE

The 66th Advanced Postgraduate Course for the American Diabetes Association (ADA) took place in New York, New York, from February 22 to 24, 2019. There, the ADA's Dr Will Cefalu moderated a panel that brought together representatives from the ADA, American College of Physicians (ACP), American Clinical Endocrinologists (ACE), and The Endocrine Society to compare and contrast treatment guidelines from each. Notably, guidelines from each organization do not agree when it comes to HbA1c targets, which emerged as a major source of discussion for the panel. Dr Silvio Inzucchi (Yale University, New Haven, Connecticut) noted that ADA guidelines3 generally target an HbA1c <7%, but this target should be individualized based on a variety of patient and disease factors. Dr Devan Kansagara (Oregon Health Science University, Portland, Oregon) explained that ACP guidelines4 recommend an HbA1c target of between 7% and 8% in most patients; the rationale behind this relatively high target is that the ACP sees little consistent evidence for a benefit with further HbA1c lowering, whereas the evidence of hypoglycemia risk is consistent and worrisome. Speaking for the ACE, Dr Guillermo Umpierrez (Emory University, Atlanta, Georgia) explained that the organization has an individualized HbA1c target: for patients without concurrent serious illness and at low risk of hypoglycemia, a target of below 6.5% is desired. Conversely, for patients with a concurrent illness and/or at risk of hypoglycemia, an HbA1c target of above 6.5% is allowable. Dr Rita Kalyani (Johns Hopkins University School of Medicine, Baltimore, Maryland), speaking for The Endocrine Society, shared that the organization has not developed any specific guidelines or glycemic targets yet, but they are currently being drafted and will hopefully be released soon.