Cardiovascular disease (CVD) is a common complication and major cause of mortality in people with type 1 diabetes (T1D). This study quantifies the prevalence of CVD among commercially insured adults with T1D in the USA from 2017 to 2021, overall and among age-defined and sex-defined subgroups. We used Merative MarketScan nationwide commercial insurance claims database (2017-2021) to identify adults ≥20 years with T1D (International Classification of Diseases, 10th Revision (ICD-10) codes). CVD ascertainment was based on ICD-10 codes for myocardial infarction, atrial fibrillation, ischemic heart disease, heart failure, peripheral artery disease, and stroke. Comorbidities included hypertension, obesity, hyperlipidemia, retinopathy, neuropathy, nephropathy, severe hypoglycemia, and diabetic ketoacidosis. Annual prevalence and age-specific and sex-specific prevalence of CVD were calculated overall and by comorbidities. Logistic regression was used to examine associations between sex, prevalent comorbidities, and odds of CVD. The sample size ranged from n=21 748 in 2017 to n=13 294 in 2021. Among adults with T1D (mean (SD) age (48.51 (13.95) years in 2017 and 46.80 (13.04) years in 2021; 47% female), the prevalence of CVD ranged from 18.18% (95% CI 17.77 to 18.66%) in 2017 to 20.58% (95% CI 19.91 to 21.24%) in 2021. In 2021, among those aged 20-39 years, 40-64 years, and 65+years, the prevalence of CVD was 4.97%, 20.41%, and 52.94%, respectively. The age-adjusted prevalence of CVD was higher in males than females (21.93% vs 19.07%). Age, sex, and all comorbidities were independently associated with CVD. Odds of CVD were highest among those with hypertension (adjusted OR 3.15, 95% CI: 2.77 to 3.57). In this sample of US commercially insured adults with T1D, CVD prevalence remained stable at ~20% from 2017 to 2021. Early detection via improved screening and targeted management of comorbidities are key preventive strategies.

Timely diagnosis of type 1 diabetes (T1D), especially in high-risk populations, is crucial for preventing serious health complications. T1D is a chronic progressive autoimmune disease that has presymptomatic stages that can be identified through the detection of islet autoantibodies. Given that T1D is associated with other autoimmune diseases, having either those diseases or a family history of them will represent a risk of T1D. From a search of the literature conducted in August 2024, we review here the evidence for the risk of either T1D or the development of T1D in association with other autoimmune diseases or a family history of those diseases. Increased risk of subsequent T1D development was identified for individuals with autoimmune diseases, including coeliac disease, autoimmune thyroid disease, autoimmune Addison's disease, juvenile idiopathic arthritis, primary biliary cholangitis, ulcerative colitis, vitiligo, and myasthenia gravis. Increased prevalence of diabetes-associated autoantibody positivity was found among non-diabetic individuals with coeliac and autoimmune thyroid diseases compared with individuals without these autoimmune diseases. Increased risk of T1D was also found for individuals with a family history of autoimmune diseases, including coeliac disease, thyroid disease, Addison's disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, autoimmune liver disease, pernicious anaemia, inflammatory bowel disease, multiple sclerosis, and granulomatosis with polyangiitis. This review highlights how certain individuals at risk of T1D can be identified to offer them islet autoantibody screening and, thereby, early detection of T1D.

Type 2 diabetes (T2D), a growing global health concern, is often exacerbated by obesity and is linked to severe complications. Serpins, a superfamily of serine protease inhibitors, that includes SerpinA3 in humans and its homolog SerpinA3k in mice. SerpinA3k regulates angiogenesis, reactive oxygen species (ROS) production, inflammation, and fibrosis particularly in the context of experimental ocular injury. Furthermore, we have previously demonstrated that urinary SerpinA3 serves as an early biomarker of kidney damage, including diabetic nephropathy; however, its functional role in renal damage, obesity, and T2D remains largely unexplored. This study explored the impact of SerpinA3k deficiency on obesity and T2D and its associated metabolic dysfunctions. Wild-type (WT, n = 27) and SerpinA3k knockout (KO n = 26) male mice were randomly assigned to three groups: standard chow diet (SD), high-fat diet (HFD) to induce obesity, and HFD combined with streptozotocin to induce T2D (D2). All the mice were followed and studied after 27 weeks. As expected, WT + D2 mice presented severe hyperglycemia, hyperinsulinemia, increased fat tissue, visceral adipocyte hypertrophy, and renal hyperfiltration. In sharp contrast, diabetic SerpinA3k-deficient mice were protected against these alterations, displaying improved glycemic control, greater pancreatic insulin content, reduced insulin resistance, and favorable adipocyte size remodeling characterized by a lower proportion of medium and large adipocytes. Additionally, these mice showed preserved lipolytic function, and attenuated renal hyperfiltration. Our findings indicate that targeting SerpinA3k mitigates hyperglycemia and insulin resistance, preserves adipose tissue functionality, and potentially prevents metabolic complications. These results highlight SerpinA3k as a promising therapeutic target for T2D.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00018-025-05922-3.

We evaluated the effectiveness of a low-carbohydrate digitally-supported weight loss programme for glycaemic control for people with type 2 diabetes (T2D) compared with usual primary care in a 12 month RCT. We individually randomised 115 people with T2D and BMI ≥27 kg/m2 recruited from 19 general practices in England, to receive either a 12-week low-carbohydrate programme with digital support, or usual care. There was no between-group difference in HbA1c change from baseline to 3 or 12 months (primary outcome; estimated mean difference (95% CI) –0.7 mmol/mol (–5.0 to 3.6), and –1.5 (–5.7 to 2.8), p = 0.80). Greater mean weight loss in the intervention group at 3 months (2.6 kg (0.6 to 4.6)) was not sustained by 12 months (–0.4 kg (–2.3 to 1.6)). While this digitally-delivered intervention was acceptable to patients, there was no evidence of a meaningful impact of the intervention on glycaemia or other cardiovascular risk factors beyond that achieved with usual care. This trial was prospectively registered at clinicaltrials.gov, NCT04916314, in June 2021.

Type 2 diabetes (T2D) represents a growing global health challenge, with its prevalence and associated metabolic complications rising sharply over the past two decades. Although the pathogenesis of T2D is complex and influenced by lifestyle and (micro)environmental factors, genetic constituents have been considered major predisposing factors. Recent literature shows significant individual variations in both the progression of T2D and the efficacy of antidiabetic drugs. These individual variations are expected to emanate from the inherent genetic make-up and potential epigenetic modifications by environmental factors. It has been proposed that altered metabolism (including cellular bioenergetic mechanisms) provides protection from T2D. Moreover, several researchers have proposed that proteins regulating cellular bioenergetics, for example, involved in adaptive thermogenesis, represent good targets to counter T2D. Therefore, we thoroughly searched the literature on genetic variability associated with T2D in this review. We could only find genes involved in (1) insulin secretion (INS, PDX1, ABCC8, KCNJ11, KCNQ1, CDKAL1, IGFBP2) and (2) cellular bioenergetics in insulin-responsive tissues (INSR, IRS, AKT, SLC2A4, TBC1D4, PPP1R3A, LEP, LEPR, ADIPOQ, TCF7L2, PPAR-γ, SLC30A8). Specific attention is given to diverse ethnic populations, in particular Indian subgroups where these genetic factors may display clearer association to T2D. By emphasizing genetic predispositions, this review highlights the lack of studies on the genetic association of cellular bioenergetics proteins in T2D pathogenesis. It also underscores the potential for early detection, personalized management, and the development of targeted therapies for individuals with T2D across different genetic profiles.

Creating an adolescent intensive health behavior and lifestyle treatment for type 1 diabetes: Feedback from the target population.

Bidirectional causal relationship between depression and Type 2 diabetes: a multi-ancestry and sex stratified Mendelian Randomization analysis.

Rationale and protocol for a randomized parallel intervention trial of two intermittent fasting approaches in patients with type 2 diabetes.

Levels of diabetes distress and its sources among older adults with type 1 diabetes and relationships to diabetes duration.

Glucagon-Like Peptide-1 Receptor Agonists and Dementia Risk Reduction in Older Adults With Type 2 Diabetes: A Retrospective Cohort Study.

Rates and Reasons for Recurrent Emergency Hospitalizations Among Frail Residents With Diabetes Following First Admission to Long-Term Care Facilities.

AI-powered hybrid self-management coaching for adults with early-onset Type 2 diabetes in Korea: A randomized clinical trial protocol.

Developing risk prediction models for type 2 diabetes and assessing the role of circulating metabolic biomarkers in five independent Finnish cohorts with over 22,000 individuals.

Genetic and transcriptional dysregulation of innate antiviral immune pathways in type 1 diabetes.

Diabetes, commonly coexisting with hypertension, notably elevates the risk of damage to target organs. Apoptosis, a critical cellular process, maintains physiological balance but its role in the etiology of diabetes remains elusive. Mendelian randomization analysis. Utilizing summary data from genome-wide association studies (GWAS) of apoptotic proteins and diabetes, a two-sample Mendelian randomization (MR) design was employed. Our analysis included the Inverse Variance Weighted (IVW), weighted median, weighted mode, and MR-Egger regression. Sensitivity analyses included MR-Egger, MR-PRESSO, Cochran's Q test, and leave-one-out analyses, aimed at assessing and confirming the robustness and reliability of the research findings. Our analysis revealed a suggestive positive correlation between increased Caspase-10 levels and heightened risk of type 1 diabetes (T1D) (OR 1.15, 95% CI 1.02-1.29, P = 0.02). Similarly, higher serum BCL2 protein levels were found to be nominally associated with an increased risk of developing type 2 diabetes (T2D) (OR 1.21, 95% CI 1.07-1.37, P = 0.003). Conversely, the BCL2L1 protein may exert a suggestive protective effect against T2D (OR 0.92, 95% CI 0.86-0.99, P = 0.03). Sensitivity analyses confirmed the reliability of these findings. Our study illuminates the genetic causal ties between apoptotic proteins and the susceptibility to essential hypertension and diabetes. These insights are foundational for advancing our comprehension of disease mechanisms, facilitating preventive measures, and opening new horizons for precision medicine targeting these pathways. The online version contains supplementary material available at 10.1007/s40200-025-01771-w.

Pancreatic islet organoids and organoids on-chip for type 1 diabetes.

Adipocyte heparan sulfate determines type 2 diabetes susceptibility in mice via FGF1-Mediated glucose regulation.

Semaglutide, a GLP-1 receptor agonist, is FDA-approved for managing type 2 diabetes (T2D) and reducing cardiovascular risk. Its off-label use in weight management and other conditions has grown, prompting a review of its benefits and risks. This review evaluates evidence on semaglutide's effects, highlighting its therapeutic potential beyond approved indications. Studies from 2021-2024 were reviewed via PubMed, ScienceDirect, and Google Scholar. Semaglutide showed promise in managing PCOS-related obesity, insulin resistance, and demonstrated renoprotective effects in diabetics and chronic kidney disease (CKD). Additionally, it improves liver enzyme levels, steatosis, and stiffness, aiding in managing Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in non-fibrotic patients. The FDA has approved it for reducing major adverse cardiovascular events, heart failure symptoms, and physical limitations in diabetic and non-diabetics. Preclinical studies suggest benefits in cognitive disorders associated with insulin resistance, including Alzheimer's disease, Parkinson's disease, and vascular dementia in animals. Although rare cases of thyroid cancer have been reported, no causal relationship has been established, emphasizing the need of caution in high-risk populations. GLP-1 therapy has also exerted protective effects against the risk of various types of cancer. However, ongoing human studies are essential to validate these findings and clarify semaglutide's association with cancer.

Dietary patterns and type 2 diabetes: A narrative review.

Diabetic nephropathy (DN) is the main cause of end-stage renal disease. The renin-angiotensin system and inflammatory pathways are suggested to contribute to renal injuries in diabetes. Endoplasmic reticulum aminopeptidase 1 (ERAP1) breaks Ang II into less harmful derivatives. This study aimed to investigate the expression level of ERAP1 and TLR4 genes in association with serum Ang II in DN patients. In 80 type 2 diabetic (T2DM) patients with nephropathy, 80 T2DM patients without nephropathy, and 60 healthy controls, polymorphisms of the ERAP1 gene (rs28096, rs34750, rs26653, rs3734016, and rs30187), as well as ERAP1 and TLR4 gene expression were evaluated with RT-PCR. Serum Ang II level was quantified using ELISA. Serum Ang II levels were significantly higher in DN patients compared to T2DM patients without nephropathy and healthy controls (P-values: 0.012 and 0.006, respectively). ERAP1 expression was also enhanced in the DN group compared to T2DM and healthy individuals (P-value: 0.033 and 0.017, respectively), and showed a significant association with Ang II levels [R: 0.43, R2: 0.184 (p-value = 0.02)]. In both patient groups, TLR4 expression was increased compared to healthy controls (P-value: 0.003 and 0.004). ERAP1 rs30187 TT was more frequent in the DN group (P-value 0.021). Increased levels of Ang II and enhanced expression of ERAP1 might be prognostic of developing nephropathy in T2DM patients.