Impact of Parental or First-Degree Family History of Diabetes on Diabetes Incidence and Progression During Long-term Follow-up in the Diabetes Prevention Program Outcomes Study.

Objective: To determine the effects of first-degree family history of diabetes on diabetes incidence in Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS) participants.

Research Design And Methods: In the DPP, adults with prediabetes were randomized to an intensive lifestyle intervention, metformin, or placebo and followed for incident diabetes. On study completion 88% of eligible DPP participants reenrolled in DPPOS for long-term follow-up.

Analysis of Long-term Follow-up of a Randomized Clinical Trial With Departures From Assigned Treatments: Estimation of Metformin Effects on Diabetes and Its Complications in the Diabetes Prevention Program Outcomes Study.

The Diabetes Prevention Program (DPP) was a 3-year randomized clinical trial (RCT) with evaluation of lifestyle and metformin interventions compared with placebo for diabetes prevention in high-risk adults. Both interventions significantly reduced diabetes incidence, prompting the long-term Diabetes Prevention Program Outcomes Study (DPPOS) to assess the progression of diabetes and its complications over 22 years. During follow-up, departures from the original metformin or placebo assignment occurred primarily because of development of diabetes that, by protocol, was managed by clinicians outside the study, after participants developed diabetes with HbA1c ≥7.

Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates.

Long-term adverse consequences of SARS-CoV-2 infection, termed "long COVID" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection.

Predictors of Initial and Sustained Glycemic and Weight Response to Tirzepatide: A Post Hoc Analysis of SURPASS-4.

We aimed to explore sustainability of lowered glycated hemoglobin (HbA1c) and weight with tirzepatide in a post hoc analysis. The question we wanted to answer was what predicted achieving and sustaining HbA1c and weight reduction in A Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk (SURPASS-4). We found greater weight loss and improved β-cell function were the main predictors for sustained glycemic control with tirzepatide therapy.

Long-term effects and effect heterogeneity of lifestyle and metformin interventions on type 2 diabetes incidence over 21 years in the US Diabetes Prevention Program randomised clinical trial.

Background: In the US Diabetes Prevention Program (DPP), a 3-year randomised clinical trial in 3234 adults with prediabetes, type 2 diabetes incidence was reduced by 58% with intensive lifestyle intervention (ILS) and by 31% with metformin, compared with placebo. We sought to assess the long-term effects and potential heterogeneity of treatment effects over approximately 21 years of follow-up.

Methods: The DPP trial was continued with protocol modifications as the DPP Outcomes Study (DPPOS).

Youth-Onset Type 2 Diabetes: What We've Learned From Key Youth-Onset Type 2 Diabetes Studies, What We Still Don't Know, and Why It Is Important.

In this review, we describe the epidemiology, pathophysiology, pediatric-specific treatment response data, morbidity, and mortality of youth-onset type 2 diabetes. In recognition of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 75th anniversary, the focus is primarily on data from three landmark youth-onset type 2 diabetes studies funded by the NIDDK in the last 20+ years. We discuss the now-recognized aggressive clinical course of youth-onset type 2 diabetes, which only recently became appreciated as a pediatric disease among health care providers.

The Normal 93: Linking the β-Cell and Insulin Sensitivity: Revisiting a 1993 Diabetes Classic by Kahn et al.

In this month's Classics in Diabetes featured article, published in Diabetes in 1993, the description by Kahn et al. of the relationship between insulin secretion and insulin sensitivity in 93 healthy adults without diabetes provided a model for the regulation of glucose tolerance that continues to be used today. In the study, data from a large sample of individuals studied with intravenous glucose tolerance tests demonstrated that in those with normal glucose tolerance, insulin secretion and sensitivity were related by a hyperbolic curve.

Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates.

Long-term adverse consequences of SARS-CoV-2 infection, termed "long COVID" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection.

SARS-CoV-2 infection is associated with higher chance of diabetes remission among Veterans with incident diabetes.

Objective: To examine the impact of SARS-CoV-2 on long-term glycemia.

Research Design And Methods: We conducted a retrospective inception cohort study using Veterans Health Administration data (March 1, 2020-May 31, 2022) among individuals with ≥ 1 positive nasal swab for SARS-CoV-2 and individuals with ≥ 1 laboratory test of any type but no positive swab. Two incident diabetes cohorts were defined based on: 1) a computable phenotype using a combination of diagnosis codes, laboratory tests, and receipt of glucose-lowering medications (n = 17,754); and 2) the presence of ≥ 2 HbA1c results ≥ 6.

Increased Steroidogenic Acute Regulatory Protein Contributes to Cholesterol-induced β-Cell Dysfunction.

Hypercholesterolemia is often observed in individuals with type 2 diabetes. Cholesterol accumulation in subcellular compartments within islet β-cells can result in insulin secretory dysfunction, which is a key pathological feature of diabetes. Previously, we demonstrated that expression of the mitochondrial cholesterol transport protein, steroidogenic acute regulatory protein (StAR), is induced in islets under conditions of β-cell dysfunction.

Associations between decreases in adiposity and reductions in HbA1c and insulin use in the Look AHEAD cohort.

Objective: The objective of this study was to elucidate associations between adiposity reduction and changes in HbA1c and insulin use among adults with type 2 diabetes and overweight or obesity.

Methods: Changes in BMI, waist circumference, and total percent fat mass were obtained over 8 years among 1316 individuals (aged 45-76 years) enrolled in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss. Generalized linear models were used to assess relationships between 5% decreases in adiposity measures with glycated hemoglobin (HbA1c) and insulin use over time.

Abdominal visceral-to-subcutaneous fat ratio in the prediction of metabolic syndrome risk in Japanese Americans followed prospectively for 10-years loses information.

Aims: Visceral fat predicts the development of metabolic syndrome (MetS), but it is not known whether the visceral to subcutaneous fat area ratio (VSR) measured using imaging predicts MetS risk as well or better. Thus, we aimed to examine if VSR predicted future risk of MetS over 10-years.

Methods: We followed 329 participants in the longitudinal Japanese American Community Diabetes Study without MetS at baseline for its development over 10 years.

The islet tissue plasminogen activator/plasmin system is upregulated with human islet amyloid polypeptide aggregation and protects beta cells from aggregation-induced toxicity.

Aims/hypothesis: Apart from its fibrinolytic activity, the tissue plasminogen activator (tPA)/plasmin system has been reported to cleave the peptide amyloid beta, attenuating brain amyloid deposition in Alzheimer's disease. As aggregation of human islet amyloid polypeptide (hIAPP) is toxic to beta cells, we sought to determine whether activation of the fibrinolytic system can also reduce islet amyloid deposition and its cytotoxic effects, which are both observed in type 2 diabetes.

Methods: The expression of Plat (encoding tPA) and plasmin activity were measured in isolated islets from amyloid-prone hIAPP transgenic mice or non-transgenic control islets expressing non-amyloidogenic mouse islet amyloid polypeptide cultured in the absence or presence of the amyloid inhibitor Congo Red.

Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials.

Background: Heart failure with mildly reduced or preserved ejection fraction (hereafter referred to as HFpEF) is the most common type of heart failure and is associated with a high risk of hospitalisation and death, especially in patients with overweight, obesity, or type 2 diabetes. In the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide improved heart failure-related symptoms and physical limitations in participants with HFpEF. Whether semaglutide also reduces clinical heart failure events in this group remains to be established.