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

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

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

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)

Management of type 1 diabetes with a very low–Carbohydrate diet: A word of caution

The public often looks to nutrition to improve health, and reporting on nutrition findings from the scientific literature in the popular media often reveals unproven benefits. Lennerz et al present data collected via an online community and conclude that exceptional glycemic control in type 1 diabetes with a low risk for adverse events is possible with a VLCD, and research is needed to confirm the generalizability of these findings. Although it may be true that a VLCD can be useful, we find the study of Lennerz et al to fall well short of the level of scientific evidence that merits the media and professional attention it seems to have garnered

Renal and Cardiovascular Effects of Sodium Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes and Chronic Kidney Disease: Perspectives on the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial Results

Background: Chronic kidney disease (CKD) risk is elevated in patients with type 2 diabetes mellitus (T2DM). Disease management in these patients has been generally focused on glycemic control and controlling other renal and cardiac risk factors as, historically, few protective therapies have been available. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation -(CREDENCE) trial of canagliflozin was the first study to demonstrate renal protection with a sodium glucose co-transporter 2 inhibitor in patients with T2DM and CKD, and these results could have important implications for clinical practice. Summary: In CREDENCE, participants with T2DM and estimated glomerular filtration rate 30-<90 mL/min/1.73 m2 and urinary albumin-creatinine ratio >300-5,000 mg/g who were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ≥4 weeks prior to randomization at either the maximum labeled or tolerated dose were randomized to receive either canagliflozin 100 mg or placebo. Canagliflozin significantly reduced the risk of the primary composite outcome of doubling of serum creatinine, end-stage kidney disease, or renal or cardiovascular (CV) death compared with placebo (hazard ratio 0.70, 95% CI 0.59-0.82; p = 0.00001). Canagliflozin also reduced the risk of secondary renal and CV outcomes. The safety profile of canagliflozin in CREDENCE was generally similar to previous studies of canagliflozin. No imbalances were observed between canagliflozin and placebo in the risk of amputation or fracture in the CREDENCE population. Key Messages: The positive renal and CV effects of canagliflozin observed in the -CREDENCE trial could have a substantial impact on improving outcomes for patients with T2DM and CKD

Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol

Diabetic ketoacidosis (DKA) is a serious complication of diabetes that occurs primarily in type 1 diabetes (T1D), although it may also affect patients with other forms of insulin-dependent diabetes and may occur in new-onset type 2 diabetes. Insulin deficiency is associated with an increase in glucagon and excessive lipolysis with increased oxidation of fatty acids to ketone bodies in the liver and ketonemia. Ketosis may advance to metabolic acidosis. For DKA to be diagnosed, both ketosis and acidosis must be present. If not recognized and/or treated early, it can become serious and life-threatening; 168,000 patients were admitted to U.S. hospitals for DKA in 2014