Reasons for Increases in Complications of Diabetes

To the Editor Dr Gregg and colleagues identified a resurgence in diabetes complications in the United States beginning in 2010 and analyzed potential underlying contributors and policy implications. However, there may be another underlying mediator of the effect that the authors did not consider

Further rise’ing to the challenge of type 2 diabetes in youth

Despite three decades of increasing prevalence of type 2 diabetes (T2D) in adolescents, the diabetes community continues to grapple with the pathophysiology of youth-onset T2D. Accumulating evidence indicates that when compared with T2D in adults, T2D in youth follows a more aggressive course. Adolescents are therefore entering adulthood with an advanced and perhaps misunderstood disease that puts them at risk for morbidity from micro- and macrovascular complications. Moreover, as the susceptibility of individuals with diabetes to poor outcomes during the coronavirus pandemic became increasingly apparent, the urgency to address the health crisis of T2D in youth has been amplified

The war is not yet won

In this issue of Diabetes Care, Selvin and Ali have done a masterful job of exploring and explaining both the rise in the incidence of diabetes over 20 years and the fall in the incidence of diabetes over the last 5 years in the U.S. You may want to skip this and just read their article. The bottom line is that we as clinicians can confirm that they, as epidemiologists, have almost certainly gotten it right. Importantly, their analysis has critical implications for policy makers

A new class of drug in the diabetes toolbox

For nearly three decades, scientists have searched for an orally active small-molecule activator of glucokinase (GK) for the treatment of diabetes, because of its central role in glucose homeostasis in the pancreas and the liver1. The first report of a potential glucokinase activator (GKA) was published in 2003, and was followed by more than 150 patents and considerable attention by the pharmaceutical industry. Progress has been hampered by predictable adverse effects that were noted in early clinical studies; however, some have persevered, leveraging medicinal chemistry to engineer away adverse features. In this issue of Nature Medicine, Zhu et al. and Yang et al. report results of the SEED and DAWN studies, respectively — two phase 3 trials evaluating the GKA dorzagliatin in patients with type 2 diabete

Maria gordon buse, MD: A family affair through six decades of diabetes discovery

Maria Gordon Buse, MD, is a product of wartime Europe. She completed her professional education in four languages on three continents and continues a nearly 60-year career as an investigator, educator, and practicing endocrinologist. This brief reprisal is written collabora-tively by her biological offspring and in-tellectual progeny, an appropriate reflection of a career where family and work were joyfully intertwined in an irresolvable way

Initial injectable therapy in type 2 diabetes: Key considerations when choosing between glucagon-like peptide 1 receptor agonists and insulin

Managing type 2 diabetes is complex and necessitates careful consideration of patient factors such as engagement in self-care, comorbidities and costs. Since type 2 diabetes is a progressive disease, many patients will require injectable agents, usually insulin. Recent ADA-EASD guidelines recommend glucagon-like peptide 1 receptor agonists (GLP-1 RAs) as first injectable therapy in most cases. The basis for this recommendation is the similar glycemic efficacy of GLP-1 RAs and insulin, but with GLP-1 RAs promoting weight loss instead of weight gain, at lower hypoglycemia risk, and with cardiovascular benefits in patients with pre-existing cardiovascular disease. GLP-1 RAs also reduce burden of glucose self-monitoring. However, tolerability and costs are important considerations, and notably, rates of drug discontinuation are often higher for GLP-1 RAs than basal insulin. To minimize risk of gastrointestinal symptoms patients should be started on lowest doses of GLP-1 RAs and up-titrated slowly. Overall healthcare costs may be lower with GLP-1 RAs compared to insulin. Though patient-level costs may still be prohibitive, GLP-1 RAs can replace 50–80 units of insulin daily and reduce costs associated with glucose self-monitoring. Decisions regarding initiating injectable therapy should be individualized. This review provides a framework to guide decision-making in the real-world setting

Experimental increase of blood glucose alters resting state EEG measures of excitation–inhibition balance

New Findings: What is the central question of this study? Glucose is the dominant energy source for the brain. However, little is known about how glucose metabolism impacts the coordination of network activity in the brain in healthy adults. What is the main finding and its importance? We demonstrate that both α oscillations and the aperiodic signal components of the resting EEG are modulated by experimentally elevated blood glucose concentrations. Our findings suggest that glucose increases measures associated with excitation–inhibition (E:I) balance, but that the effect on α oscillations might plateau. Understanding the relationship between glucose consumption and E:I balance is crucial to developing our understanding of how metabolism shapes human brain activity. Abstract: Brain network oscillations can be divided broadly into periodic and aperiodic signal components, which are sensitive to state-dependent changes in network coordination and excitation–inhibition (E:I) balance. We sought to address whether the dominant energy source of the brain, glucose, is implicated in the regulation of network activity and excitability. We conducted an experimenter-blind, crossover study of the effect of blood glucose level (BGL) on the resting EEG frequency spectrum. Participants consumed a glucose drink (75 g glucose) or an equivalent volume of water on two separate visits. EEG data were sampled before and ≤3 h after the drink. We found that the experimentally induced changes in BGL exhibited an inverted U-shaped relationship, with changes in the individual α frequency peak, whereas the slope of the aperiodic signal component of the frequency spectrum showed a positive linear association suggestive of greater excitation. In contrast, peak α power, which is typically associated with top-down inhibitory processes, was negatively associated with changes in BGL. Collectively, these results suggest that high BGL alters brain network coordination in the form of α oscillations and measures associated with E:I balance

Real-world evidence: the devil is in the detail

Much has been written about real-world evidence (RWE), a concept that offers an understanding of the effects of healthcare interventions using routine clinical data. The reflection of diverse real-world practices is a double-edged sword that makes RWE attractive but also opens doors to several biases that need to be minimised both in the design and analytical phases of non-experimental studies. Additionally, it is critical to ensure that researchers who conduct these studies possess adequate methodological expertise and ability to accurately implement these methods. Critical design elements to be considered should include a clearly defined research question using a causal inference framework, choice of a fit-for-purpose data source, inclusion of new users of a treatment with comparators that are as similar as possible to that group, accurately classifying person-time and deciding censoring approaches. Having taken measures to minimise bias ‘by design’, the next step is to implement appropriate analytical techniques (for example propensity scores) to minimise the remnant potential biases. A clear protocol should be provided at the beginning of the study and a report of the results after, including caveats to consider. We also point the readers to readings on some novel analytical methods as well as newer areas of application of RWE. While there is no one-size-fits-all solution to evaluating RWE studies, we have focused our discussion on key methods and issues commonly encountered in comparative observational cohort studies with the hope that readers are better equipped to evaluate non-experimental studies that they encounter in the future

Can we RISE to the challenge of youth-onset type 2 diabetes?

Over the past three decades, type 2 diabetes (T2D) in adolescents has become steadily more prevalent, raising the specter of increasing rates of premature micro- and macrovascular disease as affected youth move into adulthood. While T2D in adolescents is clearly linked to obesity, there is otherwise no explanation for the sudden appearance of what had previously been an adult condition in young people. Despite a steadily growing body of evidence descriptive of T2D in youth, there is a paucity of information comparing diabetic phenotypes in adults and teenagers. This issue of Diabetes Care contains three papers from the Restoring Insulin Secretion (RISE) Consortium that provide the most direct examination of this question yet, with the potential for new understanding of T2D

In reply

In Reply We thank Pimazoni-Netto et al for their letter and include our response to their concerns. In considering our published results, it is of tantamount importance that readers understand the tenets of comparative effectiveness research (CER)