In this special edition of Diabetes Core Update, Neil Skolnik discusses PATHWEIGH, a novel obesity care process for primary care clinicians which has demonstrated a decrease in population weight gain. This special episode is sponsored with support from Lilly. Presented by: Neil Skolnik, MD, Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas […]
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Special Edition: Obesity—The Changing Landscape
In the first episode of this series on Obesity, our host is joined by Dr. Mikhail Kosiborod to discuss the evolving science and cardiometabolic diseases associated with obesity. This special episode is sponsored with support from AstraZeneca. Presented by: Neil Skolnik, MD, Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; […]
Read MoreInterrupting T-Cell Memory Ameliorates Exaggerated Metabolic Response to Weight Cycling
Weight cycling has been demonstrated, in humans and animal models, to increase cardiometabolic disease and disrupt glucose homeostasis. Both obesity itself and weight cycling cause adipose tissue inflammation and metabolic dysfunction. Studies show that even after weight loss, increased numbers of lipid-associated macrophages and memory T cells persist in adipose tissue and become more inflammatory […]
Read MoreUnraveling Diabetic Cardiomyopathy (DCM): The Critical Role of the Yap–miR-22-3p–Sirt1 Axis in the Pathogenesis of DCM
Diabetic cardiomyopathy (DCM), characterized by myocardial hypertrophy and fibrosis, is a severe complication of diabetes. Activation of Yes-associated protein (Yap) has been implicated in myocardial remodeling and cardiac dysfunction. This study aimed to elucidate the role and underlying molecular mechanisms of Yap in DCM. Yap expression was evaluated in mice with type 2 diabetes mellitus […]
Read MoreKetogenic Diet and Exercise Improve Peripheral Neuropathy in a Mouse Model of Metabolic Syndrome
Metabolic syndrome (MetS) is a growing health concern that increases risk for peripheral neuropathy (PN), defined by nerve degeneration and sensory dysfunction. Although lifestyle strategies, like ketogenic diet (KD) and exercise, are known to mitigate MetS, their efficacy in maintaining nerve health or reversing established PN is less clear. First, in a maintenance paradigm, we […]
Read MorePredicting the Timing of the Metabolic Inflection Point in Type 1 Diabetes Progression Using Machine Learning and Survival Analysis Models
An inflection point (IP) marking accelerated β-cell decline occurs ∼1–2 years before type 1 diabetes diagnosis. Precisely determining this timing could optimize clinical intervention. We developed machine learning models to predict proximity to the inferred metabolic IP using oral glucose tolerance test (OGTT) data from islet autoantibody-positive individuals in the TrialNet Pathway to Prevention study. […]
Read MoreLEAP2 Reduces Ad Libitum Food Intake and Attenuates Postprandial Glucose Excursions in Men With Obesity
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 […]
Read MoreInhibition of miR-181c-5p Rescues Diabetes-Impaired Angiogenesis in Ischemia and Wound Healing
Diabetes-related vascular complications are characterized by impaired ischemia-driven angiogenesis and delayed wound healing. MicroRNAs (miRNAs) are emerging as powerful targets for multifaceted diseases. We previously identified that miRNA-181c-5p has anti-angiogenic properties, but its role in diabetes is unknown. In a hindlimb ischemia model, streptozotocin-rendered diabetic mice treated with an miRNA-181c-5p inhibitor (anti–miR-181c-5p) exhibited improved blood […]
Read MoreThe Downregulation of Type 1 Diabetes Susceptibility Gene PGM1 Induces Metabolic Imbalance and Stress in Pancreatic β-Cells
Phosphoglucomutase 1 (PGM1) is a type 1 diabetes susceptibility gene that potentially plays a key role in regulating central carbon metabolism in β-cells. Previous work suggested that β-cell PGM1 transcription is lowered after coxsackievirus B4 infection. Thus, we hypothesized that decreased PGM1 levels disrupt β-cell metabolic homeostasis and result in β-cell fragility and type 1 […]
Read MoreA Self-Reinforcing LGR5–Wnt/β-Catenin–Nedd4L Circuit Drives Fibrotic Progression in Diabetic Kidney Disease
Diabetic kidney disease (DKD) is a major cause of end-stage renal failure, driven by tubulointerstitial fibrosis. While persistent Wnt/β-catenin signaling promotes fibrosis, its sustained activation mechanism was unclear. This study, using DKD patient samples, db/db mice, and Nedd4L knockout models combined with molecular techniques, identified a key pathogenic circuit. LGR5, upregulated in diabetic kidneys, amplifies […]
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