Diabetes

This study characterized the dose effect of whey protein isolate (WPI) ingestion on glucagon secretion, glycemia, and the underlying mechanisms in adults with type 1 diabetes. Twelve insulin pump–treated adults with type 1 diabetes (mean ± SD age 47.3 ± 16.4 years; BMI 26.1 ± 3.8 kg/m2) and six adults without diabetes (age 36.2 ± 20.9 years; BMI 27.3 ± 5.8 kg/m2) received 1) control (water), 2) l…

The naturally occurring peptide, liver-expressed antimicrobial peptide 2 (LEAP2), has gained interest as a ghrelin receptor antagonist. We previously reported reduced food intake and plasma glucose–lowering effects of LEAP2 infusion in lean healthy men; however, the effects of this competitive antagonist and inverse agonist of the ghrelin receptor in men with obesity have not been investigated. I…

Metabolic syndrome (MetS) increases risk for peripheral neuropathy (PN), a progressive nerve disorder with limited treatment options. We examined whether long-term ketogenic diet (KD) could maintain nerve health, and whether KD, exercise, or both could reverse established MetS PN. Maintenance KD preserved body composition, liver health, and nerve function, while all interventions improved metabol…

We undertook this study to improve early identification of the metabolic inflection point (IP) preceding clinical type 1 diabetes in autoantibody-positive individuals. We aimed to develop and validate machine learning models using oral glucose tolerance test-derived dynamic features to detect proximity to the IP. A support vector machine trained on TrialNet Pathway to Prevention and tested on Dia…

We previously reported that transgenic overexpression of Nfkbid in NOD mice led to robust type 1 diabetes protection associated with enhanced negative selection of autoreactive T cells and expansion of regulatory T cells (Tregs) with increased suppressive capacity. The goal of this study was to further identify cellular and molecular mechanisms underlying strong protection from type 1 diabetes im…

The role of the pentose phosphate pathway (PPP) in the pathogenesis of intrahepatic lipid (IHL) accumulation has not been studied before in humans. Is the PPP, proxied by 24-h urinary erythritol, associated with IHL content at the population level? In the fully adjusted model, 24-h urinary erythritol levels were associated with higher IHL content. Furthermore, genetically predicted erythritol lev…

We undertook this study to address the persistent need for noninvasive assessment of β-cell mass in type 1 diabetes. We aimed to determine whether 18F-exendin positron emission tomography/computed tomography can reliably visualize residual β-cell mass and distinguish stages of disease. We found that pancreatic tracer uptake was consistently reduced in type 1 diabetes, differentiated insulin-depen…

We investigated the consequence of reducing GRP78 abundance in pancreatic β-cells of adult mice in normal physiological conditions. Genetic Grp78 reduction caused β-cell failure and diabetes in male mice, with weight loss, hyperglycemia, glucose intolerance, β-cell mass reduction, and β-cell dedifferentiation. Male and female mice showed similar increases in β-cell death, but proliferation was mo…

Despite advances in diabetes management, diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease. We investigated whether mesenchymal stem cells (MSCs) and their conditioned medium, containing the MSC-derived secretome, protect against DKD by modulating the mammalian target of rapamycin (mTOR)/NADPH oxidase (NOX) pathway. MSCs and MSCs-conditioned medium both reduced kidn…

Hyperglycemia and insulin resistance independently correlate with poor stroke outcomes in type 2 diabetes, although their causative role is unclear. The aim of this study was to determine experimentally whether normalizing insulin resistance rather than hyperglycemia before stroke improves stroke outcomes in type 2 diabetes. To answer this question, we specifically normalized either hyperglycemia…

Some patients with proliferative diabetic retinopathy (PDR) have poor responses to anti-vascular endothelial growth factor (anti-VEGF) therapy. This situation highlights the need for additional therapeutic approaches. In proliferative diabetic retinopathy, what is the role of ANGPTL4 that differs from VEGF? We found that ANGPTL4 is elevated in the vitreous humor of patients with PDR who are poorl…

Previous studies have demonstrated increased risk of hepatic steatosis in patients following pancreatic resection, which might be linked to decreased pancreatic function. Here, we evaluated liver fat content, circulating pancreatic hormones, amino acids, and more, before and 1 year after either total pancreatectomy or pancreaticoduodenectomy. At 1-year follow-up, we found increased liver fat cont…

Diabetic cardiomyopathy (DCM) describes the abnormality of myocardial structure and function caused by diabetes, and Yes-associated protein (Yap) is linked to various cardiovascular diseases, modulating remodeling and cardiac function in hearts, but its role in DCM is unclear. How Yap affects myocardial structure and function in mice with type 2 diabetes mellitus and the underlying pathways were …

We report five new cases of neonatal or early childhood-onset diabetes caused by biallelic pathogenic variants in IL2RA. Autoimmune diabetes was the presenting feature in most individuals and occurs in 64% of all reported cases of immunodeficiency 41. Patients typically presented in infancy with diabetic ketoacidosis, low C-peptide, and GAD antibody positivity, highlighting an autoimmune etiology…