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GLP1 receptor agonist therapies induce substantial weight loss, but up to 40% of this weight loss is lean mass, particularly muscle. Loss of muscle mass can be caused via activation of type II activin receptors ActRIIA and/or ActRIIB, and blockade of these receptors can lead to muscle growth in humans. A study in Nature Communications describes a strategy for preventing muscle mass loss during GLP1

People with diabetes mellitus experience elevated levels of stress. Learning whether dysglycaemia contributes to this effect by affecting neuronal signalling could help develop treatments that reduce anxiety in people with diabetes mellitus. A new study published in Nature Metabolism reports that in a mouse model of diabetes mellitus, increased expression of the pro-inflammatory chemokine CCL2 in neurons

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OBJECTIVE To assess time trends of and examine which sociodemographic and clinical characteristics are associated with continuous glucose monitoring (CGM) initiation in insulin-treated older adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Using data from Medicare Fee-for-Service (2013–2020) and Optum’s deidentified Clinformatics Data Mart Database (Clinformatics) (2013–2022), we identified

OBJECTIVE Exposure to maternal gestational diabetes mellitus (GDM) is associated with childhood BMI. Among youth, we explored whether three different glucagon-like peptide 1 receptor gene (GLP-1R) polymorphisms modified the associations between 1) GDM and BMI trajectories and 2) GDM and markers of glucose-insulin homeostasis. RESEARCH DESIGN AND METHODS For 464 participants from the Exploring Perinatal

Gastrointestinal hormones are essential for nutrient handling and regulation of glucose metabolism and may affect postprandial blood redistribution. In a randomized cross-over design in 10 healthy men, the involvement of glucose-dependent insulinotropic polypeptide (GIP) in splanchnic blood flow regulation was investigated using an infusion of GIP receptor antagonist (GIPR-An) GIP(3-30)NH2 during ingestion

Circulating glucagon concentrations differ between individuals with no diabetes (ND) and those with type 1 diabetes (T1D). We combined isotope dilution technique using stable tracers [6,22 13C9, 15N1]-glucagon and [6,14,19,22 13C9, 15N1]-glucagon with splanchnic and leg catheterization in participants with ND (n = 8; age 23.1 ± 2.9 years, BMI 26.6 ± 3.5 kg/m2, HbA1c 5.0 ± 0.2% [31 ± 2 mmol/mol]) and

Intraportal islet transplantation to treat insulin-dependent diabetes has been clinically validated. However, the hypoxic environment and sinusoidal architecture of the liver are unsuitable for the long-term survival of transplanted islets, leading to the loss of therapeutic effects within 1 year. The spleen has oxygen levels that meet islet needs, but intense instant blood-mediated inflammatory reactions

AIMS/HYPOTHESIS Screening for islet autoantibodies is an effective method for identifying individuals with pre-symptomatic (stage 1 and 2) type 1 diabetes. This approach offers a valuable opportunity for education and monitoring, which can help to reduce the severity of clinical manifestations at clinical onset (stage 3), including diabetic ketoacidosis. The aim of the study was to evaluate the progression

OBJECTIVE To compare the effectiveness of sodium–glucose cotransporter 2 inhibitors (SGLT2is) versus metformin in preventing delirium among patients with type 2 diabetes (T2D), using real-world data. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study using the TriNetX global health research network, including 857,171 adults with T2D who initiated either an SGLT2i (n = 88,012) or

Metabolic dysfunction–associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease (NAFLD), is a growing but often unrecognized medical problem for people with diabetes (particularly type 2 diabetes, especially when associated with obesity). Liver health has not been at the forefront of complications tracked for disease prevention, as traditionally done for diabetic

Diabetic peripheral neuropathy (DPN) poses significant clinical challenges due to progressive nerve degeneration and vascular insufficiency. To address both neural and vascular complications simultaneously, we employed an mRNA-based protein replacement therapy. In this study, leveraging mRNA template design, structure-based screening identified NGFR100W as a variant dissociating neuroprotective and

BackgroundIn gestational diabetes, one of the key factors affecting perinatal outcomes is glycaemic control. We aimed to investigate the effect of real-time continuous glucose monitoring (rtCGM) on perinatal outcomes versus self-monitoring of blood glucose (SMBG). MethodsIn this open-label, randomised, controlled trial, we recruited pregnant individuals aged 18–45 years with gestational diabetes, according

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OBJECTIVE Baricitinib preserves β-cell function in people with recently diagnosed type 1 diabetes. We aimed to determine whether simple routine clinical measures could be used to assess β-cell preservation and predict treatment response. RESEARCH DESIGNS AND METHOD Measures of β-cell function derived from clinical and biochemical measures were calculated using data from the BAricitinib in Newly DIagnosed

Metabolic resilience is essential for organismal homeostasis under diverse external pressures, because responding and adapting to stressors requires energy and drives changes at every omic level. The goal of this paper is to synthesize recent advances in understanding the intricate interplay, especially between metabolic and transcriptomic responses, involved in addressing external perturbations. We

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Aims/hypothesis Insulin resistance in obesity and type 2 diabetes is associated with elevated plasma branched-chain amino acid (BCAA) levels. Here, we examined whether the ability of insulin to clear plasma BCAAs and any influence of acute exercise or exercise training on this response are intact in obesity and type 2 diabetes. Methods In four case–control studies of participants with type 2 diabetes

Aims/hypothesis Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a cornerstone in type 2 diabetes management. In this study we evaluated heterogeneity in body weight and glycaemic responses to the initiation of liraglutide, semaglutide or dulaglutide in real-world clinical practice. Methods Data from 4467 adults with type 2 diabetes in the Diabetes Patient Follow-up (DPV) registry were analysed

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Tight glycaemic control (TGC) is known to reduce the risk and/or progression of diabetic retinopathy, a diabetes mellitus complication that causes the breakdown of the inner blood–retinal barrier (iBRB), leading to vision loss. However, intensive TGC in the early stages of diabetic retinopathy can lead to a worsening of the condition. Building on the authors’ previous work, a study in Science Translational

Aims/hypothesis Previous studies reporting lower skeletal muscle mitochondrial function in type 1 diabetes did not account for cardiorespiratory fitness, a key confounder when assessing mitochondrial function. We hypothesised that, compared with healthy individuals, muscle mitochondrial phenotypic differences would be abolished in individuals with type 1 diabetes when matched for age, sex, BMI and

The second law of thermodynamics asserts that energy within a system must be conserved, and that changes arise from alterations in energy input or output. In obesity, this principle implies that changes in body weight, where energy is stored as triglycerides in adipose tissue, result from alterations in energy intake or expenditure. To maintain a stable body weight, energy intake must balance energy

OBJECTIVE Hypoglycemia is a common complication of inpatient care for patients with diabetes. We sought to determine recent trends and demographic disparities in the rate of inpatient hypoglycemia. RESEARCH DESIGN AND METHODS We used data from the Veterans Affairs (VA) health care system to identify all patients with type 2 diabetes hospitalized from 2016 to 2022. We determined rates of inpatient hypoglycemia

Individuals with type 1 diabetes (T1D) or permanent neonatal diabetes (PND) due to an INS gene mutation (INS-PND) have a marked reduction in pancreas volume by MRI compared with control individuals with no diabetes (ND). One possible explanation for this is loss of islet-acinar insulin signaling in these forms of severe insulin deficiency. To test the hypothesis that insulin deficiency drives the loss

OBJECTIVE To investigate associations of concurrent hypertension and type 2 diabetes (T2D) with mortality in U.S. adults and elucidate differences by sex, race, and ethnicity. RESEARCH DESIGN AND METHODS The study population included 48,727 adults from the 1999–2018 National Health and Nutrition Examination Surveys. Participants were categorized into four mutually exclusive categories: 1) no hypertension

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BACKGROUND There is uncertainty regarding effect of sodium–glucose cotransporter 2 (SGLT2) inhibitors on the risk of major adverse liver-related outcomes (MALOs). PURPOSE We performed a meta-analysis of observational cohort studies to quantify the magnitude of the association between SGLT2 inhibitor use and risk of developing MALOs for people with type 2 diabetes mellitus (T2DM). DATA SOURCES We systematically

BACKGROUND Significant clinical efficacy has been shown for semaglutide in managing type 2 diabetes (T2D); however, its cost-effectiveness remains uncertain. PURPOSE To systematically review existing evidence on cost-effectiveness of semaglutide versus other T2D medications. DATA SOURCES PubMed, Embase, and the Cost-Effectiveness Analysis Registry (by 11 June 2024). STUDY SELECTION A total of 45 articles

OBJECTIVE To assess the effectiveness of Low Intensity mental health Support via a Telehealth Enabled Network (LISTEN), facilitated by diabetes health professionals, for reducing diabetes distress among adults with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS A two-arm, parallel group, pragmatic randomized controlled trial. Adults with diabetes distress (20-item Problem Areas in Diabetes

OBJECTIVE To identify metabolic signatures of insulin action/secretion in Indigenous Americans (IAs) and their association with diabetes. RESEARCH DESIGN AND METHODS We defined circulating metabolomic signatures of insulin action/secretion in 446 IAs, including glucose disposal rate during low-dose insulin clamp (Mlow) and endogenous glucose production (EGP) during insulin infusion (suppression of

Aims/hypothesis Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common feature of obesity and type 2 diabetes. Under lipotoxic stress, hepatocytes release small extracellular vesicles (sEVs) which act locally and contribute to MASLD progression, but their role in beta cell function and development of type 2 diabetes remains largely unexplored. We aimed to examine whether hepatocyte-derived

OBJECTIVE We tested associations of type 2 diabetes genetic risk score (T2D-GRS) and exposure to maternal hyperglycemia with childhood impaired glucose tolerance (IGT) and T2D and glycemic outcomes in youth from the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study. RESEARCH DESIGN AND METHODS We calculated T2D-GRS using 1,150 known genetic variants associated with T2D in adults. In utero

Insulin resistance is a central feature of metabolic disorders such as type 2 diabetes (T2D). While studies on this disorder have largely been linked to glucose metabolism and intracellular signaling, recent advances reveal that insulin resistance extends beyond traditional glucose regulatory pathways, impacting multiple organs including the brain, contributing to cognitive dysfunction and neurodegenerative

Jolliffe DA, Camargo CA Jr, Sluyter JD, et al. Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data. Lancet Diabetes Endocrinol 2025; 13: 307–20—In this Article, the affiliation for Prof Rachel E Neale has been corrected. This correction has been made to the online version as of May 16, 2025.

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Aims/hypothesis In type 1 diabetes, the counterregulatory glucagon response to low plasma glucose is impaired. The resulting increased risk of hypoglycaemia necessitates novel strategies to ameliorate alpha cell impairment. Here, we aimed to establish an in vitro type 1 diabetes-like model of alpha cell impairment using standardised reaggregated human islet microtissues (MTs) exposed to proinflammatory

Long before the word ‘inflammation’ gained prominence in immunometabolic research, Gökhan S. Hotamışlıgil and his team were investigating the molecular mechanism of a key inflammatory player, tumour necrosis factor (TNF), which drives obesity-induced insulin resistance. In the 1990s, obesity was primarily viewed as a consequence of an imbalance between caloric intake and energy expenditure, and was

OBJECTIVE To examine the ability of the 1-h plasma glucose (PG) concentration during the oral glucose tolerance test (OGTT) to predict the risk of progression to prediabetes in individuals with normal glucose tolerance (NGT). RESEARCH DESIGN AND METHODS A total of 1,557 participants from the San Antonio Heart Study who were free of type 2 diabetes at baseline, had a baseline OGTT, and had a repeat

Despite its prevalence, treatment of hypothyroidism has long divided opinion in the research and clinical fields. Here, I share my experience as a patient living with hypothyroidism for 16 years, as well as the difficulties I have faced in achieving consistent and effective treatment tailored to my individual needs.

OBJECTIVE To examine the incidence of stroke in Chinese adults with newly diagnosed type 2 diabetes (NDD), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) over a 34-year follow-up period. RESEARCH DESIGN AND METHODS This cohort study included participants with NDD, IGT, and NGT initially identified in 1986 in the Da Qing Diabetes Prevention Study who were followed up for 34 years

OBJECTIVE A number of disease-modifying therapies have been introduced for people with cystic fibrosis (CF) over the past two decades. The cumulative effects of this changing landscape on CF–related diabetes (CFRD) are unclear. We examined trends in CFRD epidemiology over time using data from the U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR). RESEARCH DESIGN AND METHODS CFFPR data from 2003

The rising prevalence of depressive disorder worldwide requires better interventional avenues. B vitamins are gaining increasing interest as potential therapeutic approaches in this context given current evidence for a bidirectional association between B vitamin deficiency and depressive disorder. We discuss how B vitamins and B vitamin-associated probiotic supplementation may represent an effective

BackgroundAdrenal incidentalomas are found in 3–10% of adults undergoing abdominal imaging. Of these, 30–50% are responsible for mild autonomous cortisol secretion (MACS), which is frequently associated with hypertension. The impact of adrenalectomy on hypertension in patients with unilateral incidentalomas and MACS remains uncertain. The aim of the CHIRACIC study was to prospectively assess the impact

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Breast cancer (BC) remains the most prevalent malignancy among women worldwide. While genetic predisposition and reproductive history are key contributors to its development, modifiable risk factors are also important, particularly those linked to lifestyle behaviors, often influencing the endogenous metabolome. Over the past decade, mass spectrometry-based metabolomics has enabled agnostic investigations

Aims/hypothesis Efficient prediction of clinical type 1 diabetes is important for risk stratification and monitoring of autoantibody-positive individuals. In this study, we compared type 1 diabetes predictive models for predictive performance, cost and participant time needed for testing. Methods We developed 1943 predictive models using a Cox model based on a type 1 diabetes genetic risk score (GRS2)

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Breast cancer remains the most commonly diagnosed malignancy among women worldwide. While breast cancer treatment outcomes have improved in recent years there remains an unmet medical need for therapeutics that can be used with curative intent in the most aggressive breast cancer subtypes and for those cancers that have metastasized. In recent years, the success of T-cell-based therapies and other

OBJECTIVE To examine associations of serum imidazole propionate (ImP), histidine, and their ratio with incident type 2 diabetes (T2D) and related dietary and gut microbial factors in U.S. Hispanic/Latino people. RESEARCH DESIGN AND METHODS In the Hispanic Community Health Study/Study of Latinos, we evaluated serum ImP, histidine, and ImP-to-histidine ratio at baseline (2008–2011) and their cross-sectional

The foundations for modern medical treatments for diabetes mellitus and obesity were laid more than 60 years ago by several scientific groups in London. Importantly, the 1965 publication of Intestinal factors in the control of insulin secretion by McIntyre and colleagues investigated both glucose metabolism and the role of the liver. This work contributed markedly to the discovery of the incretin effect

Increasing numbers of transgender and nonbinary youth are now accessing gender-affirming medical interventions, which have been demonstrated to improve health and well-being. This Perspective addresses how the needs of transgender and nonbinary youth, up to age 18, can be addressed through individualized gender-embodiment care. We first review standard medical therapies, including gonadotropin-releasing