Youth-onset type 2 diabetes is a heterogeneous disease with increasing prevalence in relation to increased rates of obesity in children. It has genetic, epigenetic, social, and environmental determinants. Youth-onset type 2 diabetes is alarming given a rapidly progressive course compared with the course of adult-onset disease, early-onset vascular complications, and long-term exposure to hyperglycemia

OBJECTIVE To explore how the commercially available large language model (LLM) GPT-4 compares to endocrinologists when addressing medical questions when there is uncertainty regarding the best answer. RESEARCH DESIGN AND METHODS This study compared responses from GPT-4 to responses from 31 endocrinologists using hypothetical clinical vignettes focused on diabetes, specifically examining the prescription

Treatment of classic congenital adrenal hyperplasia (CAH) is directed at replacing deficient hormones and reducing androgen excess. However, even in the era of early diagnosis and lifelong hormonal substitution, the presence of CAH is still associated with numerous complications and also with increased mortality. The aim of this article was to create an authoritative and balanced review concerning

In the article cited above, incorrect affiliation information was given for author Linda A. DiMeglio. The correct affiliation for Linda A. DiMeglio is Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN. The online version of the article (https://doi.org/10.2337/dci24-0042) has been updated to correct the error.

OBJECTIVE Diabetes affects 537 million people globally, with 34% expected to develop foot ulceration in their lifetime. Diabetes-related foot ulceration causes strain on health care systems worldwide, necessitating provision of high-quality evidence to guide their management. Given heterogeneity of reported outcomes, a core outcome set (COS) was developed to standardize outcome measures in studies

The gut microbiota influences aspects of metabolic disease, including tissue inflammation, adiposity, blood glucose, insulin, and endocrine control of metabolism. Prebiotics or probiotics are often sought to combat metabolic disease. However, prebiotics lack specificity and can have deleterious bacterial community effects. Probiotics require live bacteria to find a colonization niche sufficient to

OBJECTIVE We explored the potential value of continuous glucose monitoring (CGM) in early pregnancy in predicting gestational diabetes mellitus (GDM) and pregnancy outcomes. RESEARCH DESIGN AND METHODS The study recruited 103 multiethnic Asian pregnant women with overweight/obesity from a hospital-based, prospective cohort. All of them had worn blinded CGM devices in early pregnancy and underwent the

OBJECTIVE Gestational diabetes mellitus (GDM) is known to be associated with certain respiratory impairments in offspring. However, the specific association between maternal GDM and childhood lung function remains unclear. We examined the association of maternal glycemia, as measured by oral glucose tolerance test (OGTT) values, with childhood lung function outcomes in a birth cohort. RESEARCH DESIGN

Aging is a major risk factor for a variety of diseases, thus, translation of aging research into practical applications is driven by the unmet need for existing clinical therapeutic options. Basic and translational research efforts are converging at a critical stage, yielding insights into how fundamental aging mechanisms are used to identify promising geroprotectors or therapeutics. This review highlights

Metformin, an oral antihyperglycemic drug that has been in use for over 60 years, remains a first-line therapy for type 2 diabetes (T2D). Numerous studies have suggested that metformin promotes health benefits beyond T2D management, including weight loss, cancer prevention and treatment, and anti-aging, through several proposed mechanistic targets. Here we discuss the established effects of metformin

OBJECTIVE In the general population, continuous glucose monitoring (CGM) provides convenient and less-invasive glucose measurements than conventional self-monitored blood glucose and results in reduced hypo-/hyperglycemia and increased time-in-target glucose range. However, accuracy of CGM versus blood glucose is not well established in hemodialysis patients. RESEARCH DESIGN AND METHODS Among 31 maintenance

Identifying neurological mechanisms that regulate feeding behaviour could help to advance the treatment and prevention of obesity and eating disorders. New research in mice has identified and localized a population of neurons that promotes eating to satiate hunger and reduces the desire to eat simply for pleasure. One subset of these DBBPENK neurons projects from the DBB to the paraventricular nucleus

Gene therapy holds tremendous promise for treating a wide range of hereditary and acquired diseases by delivering exogenous therapeutic nucleotide sequences into specific cells or tissues. Recent advances support the notion that gene therapy could offer a long-term cure for diabetes mellitus, something that current conventional pharmacotherapies cannot achieve.

Astrocytes, the predominant glial cell type in the mammalian brain, influence a wide variety of brain parameters including neuronal energy metabolism. Exciting recent studies have shown that obesity and diabetes can impact on astrocyte function. We review evidence that dysregulation of astrocytic lipid metabolism and glucose sensing contributes to dysregulation of whole-body energy balance, thermoregulation

In the abstract cited above, author Nadine El Kalach was inadvertently omitted from the author list. The full, correct author list is as follows: Nadine El Kalach, Emmanuel F. Julceus, Caroline Rudisill, Faisal Malik, Kate Flory, Edward A. Frongillo, Katherine A. Sauder, Jason A. Mendoza, and Angela D. Liese. All authors approve the addition and the order of the revised author list. The authors apologize

OBJECTIVE Diabetes is a well-known risk factor for dementia. We investigated the association between (pre)diabetes and older brain age and whether this can be attenuated by modifiable lifestyle behaviors. RESEARCH DESIGN AND METHODS The study included 31,229 dementia-free adults from the UK Biobank between the ages of 40 and 70. Glycemic status (normoglycemia, prediabetes, or diabetes) was ascertained

Evaluation of insulin secretory capacity is essential to understand the pathophysiological condition of individuals with diabetes and to assess the efficacy of drugs used in treatment of the disease. The 1 mg intravenous glucagon stimulation test (GST) is widely used to evaluate residual β cell function; we previously reported that GST assessment of insulin secretory capacity is useful in assessing

It is well known that adipocytes are heterogeneous, and research about how best to identify and categorize adipocyte subclasses is ongoing. Thermogenic adipocytes are generally identified by the presence of UCP1; the futile creatine cycle is also an important thermogenic process in these cells. However, a lack of suitable models — particularly for beige adipose tissue — has stalled research into the

OBJECTIVE Multiregional trials are designed under the assumption that treatment effect applies to the entire target population, yet several factors may introduce geographic heterogeneity in treatment effect. We explored whether such variations exist in trials assessing the efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in major cardiovascular events (MACE) in type 2 diabetes. RESEARCH

BACKGROUND Racial and ethnic disparities in type 2 diabetes outcomes are a major public health concern. Interventions targeting multiple barriers may help address disparities. PURPOSE To conduct a systematic review and meta-analysis of diabetes self-management education (DSME) interventions in minority populations. We hypothesized that interventions addressing multiple levels (individual, interpersonal

Despite sharing incretin activity with glucagon-like peptide 1 (GLP-1), the development of gastric inhibitory polypeptide (GIP)-based drugs has been hindered by the minor effects of native GIP on appetite and body weight and genetic studies associating loss-of-function with reduced obesity. Yet, pharmacologically optimized GIP-based molecules have demonstrated profound weight lowering benefits of GIPR

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme for redox reactions and regulates cellular catabolic pathways. An intertwined relationship exists between NAD+ and mitochondria, with consequences for mitochondrial function. Dysregulation in NAD+ homeostasis can lead to impaired energetics and increased oxidative stress, contributing to the pathogenesis of cardiometabolic diseases.

OBJECTIVE This study was conducted to evaluate the effects of early clinical diagnosis of type 1 diabetes by comparison of clinical parameters at diagnosis and during follow-up in patients with pediatric type 1 diabetes with early, intermediate, and late diagnosis. RESEARCH DESIGN AND METHODS In a population-based analysis, data on 14,292 pediatric patients with type 1 diabetes diagnosed between 2015

Very-low-density lipoprotein (VLDL), a triglyceride-rich lipoprotein secreted by hepatocytes, is pivotal for supplying peripheral tissues with fatty acids for energy production. As if walking on a tightrope, perturbations in the balance of VLDL metabolism contribute to cardiometabolic dysfunction, promoting pathologies such as cardiovascular disease (CVD) or metabolic dysfunction-associated steatotic

Liver diseases represent a growing global health challenge, and the increasing prevalence of obesity and metabolic disorders is set to exacerbate this crisis. To meet evolving regulatory demands, patient-specific in vitro liver models are essential for understanding disease mechanisms and developing new therapeutic approaches. Organoid models, which faithfully recapitulate liver biology, can be established

Pancreatic β-cell dysfunction caused by obesity can be associated with alterations in the levels of microRNAs (miRNAs). However, the role of miRNAs in such processes remains elusive. Here, we show that pancreatic islet miR-27a-5p, which is markedly increased in obese mice and impairs insulin secretion, is mainly delivered by visceral adipocyte-derived extracellular vesicles (EVs). Depleting miR-27a-5p

In healthy individuals, the majority of cortisol secretion occurs within several hours surrounding morning awakening. A highly studied component of this secretory period is the cortisol awakening response (CAR), the rapid increase in cortisol levels across the first 30-45 min after morning awakening. This strong cortisol burst at the start of the active phase has been proposed to be functional in preparing

The widespread use of per- and polyfluoroalkyl substances (PFASs), and their resistance to degradation, renders human exposure to them inevitable. PFAS exposure disturbs endocrine function, potentially affecting cognitive development in newborns through thyroid dysfunction during pregnancy. Recent studies reveal varying male and female reproductive toxicity across PFAS classes, with alternative analogs

Glucocorticoids (GCs) are potent anti-inflammatory drugs. A new study by Auger et al. found that GCs increase itaconate, an anti-inflammatory tricarboxylic acid (TCA) cycle intermediate, by promoting movement of cytosolic pyruvate dehydrogenase (PDH) to mitochondria. Itaconate was sufficient for mediating the anti-inflammatory effects of GCs in mice, overriding the notion that nuclear glucocorticoid

Our limited understanding of metabolic aging poses major challenges to comprehending the diverse cellular alterations that contribute to age-related decline, and to devising targeted interventions. This review provides insights into the heterogeneous nature of cellular metabolism during aging and its response to interventions, with a specific focus on cellular heterogeneity and its implications. By

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus which is associated with visual loss and blindness worldwide. However, the effective treatments for both early- and late-stage DR remains lacking. A streptozotocin (STZ)-induced diabetic mice model and high glucose (HG)-treated Müller cell model were established. M1/M2 microglia polarization was assessed by immunofluorescence

Two recent studies have unravelled novel modes of glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling regulation. Kizilkaya et al. characterized the effect of changes in β-arrestin 2 coupling with naturally occurring GIPR coding variants, whereas Regmi et al. investigated GIPR expression profiles and functional regulation in adipocytes.

Leptin is a homeostatic regulatory element that signals the presence of adipocyte energy stores, reduces food intake, and increases energy expenditure. Similarly, serotonin (5- HT), a signaling molecule found in both the central and peripheral nervous systems, also controls food intake. Using neuronal tract-tracing, pharmacological and optogenetics approaches, and in vivo microdialysis, combined with

The approval of teplizumab to delay the onset of type 1 diabetes is an important inflection point in the decades long pursuit to treat the cause of the disease rather than its symptoms. NIDDK convened a workshop of the Diabetes Mellitus Interagency Coordinating Committee titled “Evolving Concepts in Pathophysiology, Screening, and Prevention of Type 1 Diabetes” to review this accomplishment and identify

Diabetic peripheral neuropathy (DPN) affects around 50% of the 500 million people with type 2 diabetes worldwide and is considered disabling and irreversible. The present study was undertaken to assess the effect of metformin on peripheral neuropathy outcomes in type 2 diabetes. 69 type 2 diabetes participants receiving metformin were recruited and underwent clinical assessment, peripheral nerve ultrasound

The translocon-associated protein-δ (TRAPδ) plays a role in insulin biosynthesis within pancreatic β cells. However, its pathophysiological significance in maintaining islet β cell function and glucose homeostasis remains unclear. In this study, we generated a mouse model featuring pancreatic β cell-specific deletion of TRAPδ (TRAPδ βKO). Our findings revealed that TRAPδ βKO resulted in decreased circulating

Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and