Socioeconomic position and type 2 diabetes: The mediating role of physical work environment - the Maastricht study.

Young adults (aged ≤ 40 years) are underrepresented in clinical trials that investigate interventions for those living with Type 2 diabetes (T2D). This study evaluated the efficacy of semaglutide treatment in young adults with T2D by examining the effects on HbA1c and body weight (BW) during the SUSTAIN and PIONEER programmes compared to placebo and active comparators, according to age at study enrolment. This study also assessed aggregated safety data across age subgroups. This post hoc analysis of the SUSTAIN (once-weekly subcutaneous administration) and PIONEER (once-daily oral administration) programmes assessed the efficacy of semaglutide treatment in different age subgroups by comparing change in HbA1c and BW between young adults with T2D (≤ 40 years), middle-aged adults with T2D (> 40- ≤ 50 years), and middle older-aged adults with T2D (> 50 years). Selected safety outcomes were assessed, focusing on serious adverse events (SAEs) and gastrointestinal SAEs from the programmes. Findings indicate a reduction in HbA1c levels and BW in participants across all age subgroups that were treated with semaglutide, particularly in young adults versus other age subgroups. The proportion of participants experiencing SAEs was overall comparable between semaglutide treatment and comparators across age subgroups and administration route. Semaglutide shows notable and consistent efficacy in reducing HbA1c and BW across all age subgroups with T2D, including young adults. Effective glucose- and weight-lowering interventions in people living with T2D at an earlier stage in life may reduce the high risk of future health complications associated with developing T2D as a younger adult.

We aimed to determine whether muscular fitness, focussing on power-related components, is reduced in adults with type 1 diabetes (T1D) compared with the group without T1D. Adults with T1D and healthy controls were enroled in the study. Muscular fitness was evaluated using Handgrip strength (HG), knee extensor isometric maximal torque (PeakT), and 10-repetition sit-to-stand (STS). Moreover, the specific power index of the lower limb was obtained from the ratio between STS and skeletal muscle mass. Sixty-seven individuals with T1D (32 females, 35 males; age: 38.9±14.6years) were matched for age, sex, body mass index and physical activity level with a non-diabetic Control Group (CG, n=67). The T1D group was significantly slower than the control group (CG) during the STS test (20.2±3.8vs. 18.6±3.3s, p<0.01) and exhibited a lower specific power (5.3±1.2 vs. 5.9±1.3 W/kg, p<0.01). No significant differences were observed in HG and PeakT (p>0.05) between the T1D and CG groups. Adults with T1D show a reduction in dynamic muscle function (STS), whereas isometric function appears to be preserved.

Obesity and overweight are major contributing factors for type2 diabetes (T2D). Here, we explored the perspectives of people with T2D on the value and expected impacts of reaching a lower weight. Adult residents of Canada with T2D completed a cross-sectional survey informed by qualitative interviews. Survey questions explored weight management experiences, T2D and weight impacts on quality of life, and the value of losing 5%, 10%, or 20% body weight. Results were summarized descriptively. Of 358 participants, 56% were male and 81% were white, with a mean age of 59years (SD 13) and a mean self-reported body mass index of 32.9kg/m2 (SD 7.9); 44% of participants had a current hemoglobin A1C < 7%. T2D negatively affected quality of life, particularly impacting emotional well-being (50%), other illnesses (48%), and sleep (49%). Most participants believed their weight affected their T2D (85%), felt they needed to lose weight (89%), struggled to lose weight (79%), and deemed weight management to be crucial for T2D management (94%). Participants' average "dream" weight loss was a 19% reduction. Most participants anticipated losing 5%, 10%, or 20% body weight would significantly improve their future with T2D (64%, 75%, or 71%) and overall health (79%, 85%, and 90%), and would have a positive impact (70%, 78%, or 71%), particularly on appearance, comorbidities, and emotional well-being. Participants with T2D valued weight loss and anticipated improvements to their health and quality of life with greater perceived value and impacts associated with increased weight reductions.

Insufficient access to healthy food has been linked to poor health outcomes in under-resourced communities. The relationship between neighborhood-level food insecurity and diabetes in pregnancy remains understudied, with previous studies reporting inconsistent results. This study examined the association between living in a low-income, low access (LILA) census tract and the prevalence of pregestational type 2 diabetes (T2D) and gestational diabetes (GDM) among pregnant individuals. This cross-sectional study included patients who delivered a singleton pregnancy at ≥20 weeks' gestation at Henry Ford Hospital between January 2014 and December 2019 and resided within Detroit city limits at the time of delivery. Residence in a LILA census tract, as designated by the USDA Food Access Research Atlas, was the exposure, and prevalences of pregestational T2D and GDM were the outcomes, which were collected retrospectively from patient records. A total of 117 census tracts were designated as LILA. Covariates that were adjusted for included maternal age at delivery, race, body mass index (BMI), insurance status, and substance use during pregnancy (drug, alcohol, and tobacco). Multivariate logistic regression models were used to analyze the data. Of the 3,897 patients included in this study, 1,377 (35.3%) resided in LILA tracts and 2,520 (64.7%) resided in non-LILA tracts. When individuals residing in LILA and non-LILA tracts were compared, there were no significant differences in the prevalences of pregestational T2D (4.8 vs. 4.6%, adjusted prevalence odds ratio [aPOR] = 1.00, 95% CI: 0.72-1.38, p = 0.99) and GDM (11.3 vs. 13.7%, aPOR = 0.96, 95% CI: 0.78-1.20, p = 0.74). Maternal age at delivery, maternal BMI, race, and insurance status were all significantly associated with the prevalences of GDM and pregestational T2D. Our results suggest that a LILA tract is not significantly associated with the prevalences of T2D and GDM during pregnancy. · Living in a LILA tract was not linked with GDM or T2D in pregnancy.. · Age and BMI were significantly associated with T2D and GDM.. · Race and insurance status were significantly associated with T2D and GDM..

Semaglutide has previously been approved for weight management and cardiovascular disease as a subcutaneous formulation, and more recently also as an oral formulation. However, there is limited information across oral dose levels, and there are no studies for the 25 mg dose in people with obesity and type 2 diabetes (T2D). To fulfil health authority approval requirements, population pharmacokinetic and exposure-response analyses were used to extrapolate efficacy and safety data from subcutaneous to oral semaglutide. Once-daily oral semaglutide 25 mg was approved for obesity treatment based on historical semaglutide data and the OASIS programme. Two studies were simulated: a modelled/virtual Phase 2 trial to establish efficacy across different oral semaglutide dose levels, and a modelled/virtual Phase 3 trial to assess efficacy in a population with overweight/obesity and T2D. Most participants (82.2%) treated with oral semaglutide 25 mg in OASIS 4 achieved exposure levels within the same range as participants treated with once-weekly subcutaneous semaglutide 2.4 mg in STEP 1. In the simulated studies, oral semaglutide 25 mg provided significantly greater weight reduction compared with placebo, for the trial product estimand and treatment policy estimand, respectively, in those with overweight/obesity and T2D (9.4% and 7.8%), and in those with overweight/obesity without T2D (16.3% and 14.7%). Estimated exposure levels and efficacy observed with oral semaglutide 25 mg were similar to those obtained with subcutaneous semaglutide 2.4 mg, supporting application of oral semaglutide 25 mg to treat individuals with overweight/obesity, with/without T2D.

Obesity is characterised by pathological alterations in visceral white adipose tissue (vWAT) that may contribute to thedevelopment of type 2 diabetes (T2D). While microRNAs (miRNAs) are key post-transcriptional regulators, comprehensive human vWAT profiling across metabolic states remains limited. This study characterised vWAT miRNA expression in lean, obese and obese+T2D individuals to identify obesity-driven regulatory networks associated with metabolic dysfunction. Deep miRNA sequencing was performed on vWAT samples from a discovery cohort comprising lean controls and individuals with obesity (with and without T2D). Findings were validated via RT-qPCR in an independent replication cohort. Differentially expressed miRNAs were bioinformatically integrated with matched mRNA transcriptomic data to construct putative functional regulatory associations and identify enriched pathways underlying metabolic impairment. The dominant transcriptomic signal was driven by obesity rather than T2D status, with substantial overlap between obese subgroups in principal component analyses. miR-141-3p, miR-200b-3p, miR-12 136 and miR-585-3p showed consistent differential expression associated with obesity. miR-141-3p and miR-200b-3p were upregulated and inversely associated with metabolic stress-related genes, including TF and FBXO32. Integrated miRNA-mRNA analyses revealed putative regulatory associations involving inflammation, lipid metabolism, insulin signalling and iron homeostasis. These associations were robust across progressive covariate adjustment models for age and sex. This study provides a comprehensive characterisation of the vWAT miRNA landscape predominantly shaped by obesity, with T2D contributing comparatively subtle additional variation. We identified putative miRNA-mRNA regulatory associations that may contribute to pathological adipose tissue dysfunction. These findings highlight candidate molecular regulators worthy of further functional investigation in the context of obesity and T2D.

Associations of grip strength and muscle mass with incident complications in patients with type 2 diabetes: a prospective cohort study.

In a phase 2 trial, the efficacy and safety of the highly selective aldosterone synthase inhibitor vicadrostat, alone or with empagliflozin, were investigated in people with chronic kidney disease (CKD) with or without type 2 diabetes (T2D). Adults (n = 586) with CKD (estimated glomerular filtration rate [eGFR] 30 to < 90 mL/min/1.73 m2, urine albumin-creatinine ratio [UACR] 200 to < 5000 mg/g) receiving a maximally tolerated dose of renin-angiotensin system inhibitor were randomised to receive vicadrostat (3, 10 or 20 mg) or matching placebo for 14 weeks, with or without background empagliflozin. The primary outcome, effect on albuminuria at 14 weeks, as well as systolic blood pressure (SBP) and eGFR, was assessed by T2D and obesity subgroups (body mass index [BMI]: ≥ 30 vs. < 30 kg/m2) at baseline. Consistent with overall study results, the largest UACR reductions were observed in 10 and 20 mg dose groups across both subgroup analyses (adjusted mean reduction 30%-51% vs. 37%-46% in the overall study). UACR reductions were consistent in participants with and without T2D (PINTERACTION = 0.53 and 0.40 with/without empagliflozin, respectively) and irrespective of BMI category at baseline (PINTERACTION = 0.35 and 0.44 with/without empagliflozin, respectively). Effects of vicadrostat treatment on reductions in eGFR and SBP were also consistent across T2D and BMI subgroups. Effects of vicadrostat with or without empagliflozin on UACR, eGFR, and SBP were consistent irrespective of T2D and obesity status. ClinicalTrials.gov identifier: NCT05182840.

The glucose monitoring comparison in primary care study (GluCoCare): Study design, methods, recruitment success, and baseline characteristics of study participants.

Predominantly genetic, intrauterine, and lifestyle aetiologies of type 2 diabetes are associated with distinct clinical presentations and risk of complications: a Danish cross-sectional and follow-up study.

Evidence on cardiovascular/renal outcomes associated with GLP-1-based therapies in type 1 diabetes (T1D) is limited. We examined the effects of GLP-1-based therapy on major clinical outcomes and safety, including diabetic ketoacidosis (DKA) and hypoglycemia risk, in adults with T1D in a large real-world cohort. This retrospective cohort study utilised the TriNetX global health research network. Adults with T1D were classified by exposure to GLP-1-based therapies. Propensity score matching (1:1) balanced baseline characteristics for age, sex, demographic characteristics, cardiometabolic risk factors, comorbidities, medication use, and laboratory parameters including lipid profile and glycemic control. Outcomes included all-cause mortality, myocardial infarction, cerebral infarction, heart failure (HF), adapted major adverse cardiovascular events (MACE-all CV clinical outcomes), chronic kidney disease (CKD), and all-cause hospitalisation, plus safety outcomes (hypoglycemia and DKA). Event accrual began 6 months after therapy initiation. After matching, 4088 individuals per group were included. GLP-1-based therapy was associated with lower risks of all-cause mortality (HR 0.67, 95% CI 0.46-0.98), HF (HR 0.38, 95% CI 0.21-0.67), adapted-MACE (HR 0.61, 95% CI 0.40-0.94) and all-cause hospitalisation (HR 0.70, 95% CI 0.51-0.96). No significant differences were observed for myocardial infarction, ischemic stroke, or CKD. DKA incidence was not increased, while hypoglycemia risk was lower with GLP-1 therapy (HR 0.72, 95% CI 0.55-0.95). Less than 10 (0.2%) events of pancreatitis were noted in both groups. In this propensity score-matched real-world cohort of adults with T1D, GLP-1-based therapy was associated with lower risks of all-cause mortality, HF, adapted-MACE, hospitalisation, and hypoglycemia without increased DKA risk. Randomised controlled trials are needed to confirm these findings.

Type 1 diabetes (T1D) is a chronic autoimmune disease that disproportionately affects children and adolescents and is associated with substantial medical and psychosocial burden. Despite advances in insulin delivery systems and continuous glucose monitoring, most patients do not achieve optimal glycemic control and remain at risk for diabetic ketoacidosis, long-term microvascular and macrovascular complications, and premature mortality. Increasing evidence demonstrates that T1D is a progressive disease characterized by years of asymptomatic autoimmunity and gradual pancreatic beta-cell loss, creating an opportunity for early disease-modifying intervention. This review summarizes the genetic and immunologic foundations of T1D, the disease classification system, and emerging strategies aimed at preserving endogenous insulin production. Particular focus is given to teplizumab (Tzield), an anti-CD3 monoclonal antibody that is the first FDA-approved therapy shown to delay progression from stage 2 to stage 3 T1D in individuals ages 8 years and older. Disease-modifying immunotherapies such as teplizumab represent a paradigm shift in T1D management, with the potential to delay disease onset and reduce long-term complications.

Behaviour change techniques and physical activity outcomes in interventions for children with type 1 diabetes: A scoping review.

High LDL-cholesterol in children and adolescents with type 1 diabetes: the impact of body adiposity and sex.

Within the cardiovascular-kidney-metabolic syndrome (CKM) framework, semaglutide has demonstrated benefits beyond glycemic control and weight loss in clinical trials. However, most real-world studies in type 2 diabetes (T2D) have limited assessment of broader cardiometabolic and renal outcomes. We evaluated CKM-relevant outcomes among individuals with T2D who achieved substantial hemoglobin A1c (HbA1c) and weight improvements after initiating semaglutide in real-world settings. This observational pre-post study used Optum's de-identified Market Clarity Data from January 1, 2007, to June 30, 2024. The primary cohort comprised individuals with T2D who achieved glycemic control (HbA1c < 7%) and weight loss (≥ 5%) goals after semaglutide initiation. We compared baseline (1 year before initiation) with 1st-year and 2nd-year follow-up for cardiometabolic endpoints (3-point and 5-point major adverse cardiovascular events [MACE]), cardiometabolic risk factors, and renal outcomes. Sensitivity analysis was performed in an exploratory cohort of patients in the top tertile of Hb1Ac reduction and weight loss. We identified 413 patients in the primary cohort (mean age 59.6years and balanced sex distribution). Significant reductions were observed in low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), total cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure and high-density lipoprotein cholesterol (HDL-C) increased at both 1 and 2 years after semaglutide initiation (all p < 0.001). Fewer than 1% of patients experienced a ≥ 40% decline in estimated glomerular filtration rate (eGFR) during follow-up. Mean change in urine albumin-to-creatinine ratio (UACR) were - 20.13mg/g in the 1st year (p < 0.001) and - 54.03mg/g in the 2nd year (p < 0.001). The event rate of 3-point MACE decreased from 26.82 per 1000 person-years (PY) during baseline to 22.31 per 1000 PY in the 2nd year. The sensitivity analysis showed consistent results. In this real-world study, semaglutide users who achieved glycemic and weight goals exhibited marked improvements in cardiometabolic and renal outcomes over 2 years.

Although type 1 diabetes (T1D) technology has improved health outcomes for many, some people continue to experience severe hypoglycemic events (SHEs).This study reviews the history of SHEs and impaired awareness of hypoglycemia (IAH) compound risk for future SHEs, and describes the lived experiences of SHEs among adult people with T1D (pwT1D) with recurrent SHEs (≥ 2/year) and IAH who use continuous glucose monitors (CGMs). In this online survey study with eligible CGM-users from the T1D Exchange Registry, participants were asked open-ended questions on the impact of SHEs on their lives, then responses were analyzed thematically. Participants reporting ≥ 2 SHEs in the last year and IAH were included in the analytic sample. Participant (n = 158) responses were coded into 12 thematic categories. A total of 82% of participants reported one or more of the following themes: Emotional and Psychological Impact of SHEs, Social/Relationships Impacts, and Attempts to Prevent and Cope. Specifically, nearly half of participants described the Emotional and Psychological Impact of SHEs (49.4%), with fear around hypoglycemia being especially prominent (e.g., "I worry I might pass out and not wake up…"). Over one-third of participants described impacts of SHEs on their Social Relationships (33.5%), including increased distress from their loved ones. Remaining themes described impacts on numerous other domains of life. Adult pwT1D using CGMs who had recurrent SHEs and IAH experience substantial burden in their daily lives. New therapeutic options to help this population eliminate SHEs and meet T1D treatment goals would be especially beneficial.

Although sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiorenal benefits, direct comparisons between dapagliflozin and empagliflozin-the two most commonly used and studied agents in this class-remain limited, particularly in patients with advanced chronic kidney disease (CKD). In the current study, we aimed to compare the cardiorenal effectiveness and safety of dapagliflozin versus empagliflozin in adults with type 2 diabetes (T2D) and stage 3B-5 CKD. We used the TriNetX network and identified adults with T2D and stage 3B-5 CKD newly initiating dapagliflozin or empagliflozin. Following a target trial emulation framework, we applied 1:1 propensity score matching and Cox proportional hazards models to estimate hazard ratios (HRs) for major adverse kidney events (MAKE), major adverse cardiovascular events (MACE), all-cause mortality, and adverse events. After matching, 4,361 participants were included per group. The mean age was 67.6-67.9 years and men comprised 45.3-45.9% with a median follow-up duration of 780-790 days. Dapagliflozin users showed comparable HRs for MAKE (1.04; 95% CI: 0.94-1.16), MACE (1.02; 95% CI: 0.95-1.09), all-cause mortality (0.86; 95% CI: 0.74-1.00), and adverse events (1.03; 95% CI: 0.92-1.14). However, the risk of end-stage kidney disease (ESKD) was higher with dapagliflozin (1.28; 95% CI: 1.11-1.48). We concluded that in adults with T2D and advanced CKD, dapagliflozin and empagliflozin demonstrated comparable cardiorenal effectiveness and safety. Dapagliflozin was associated with a modestly higher ESKD risk, but this finding warrants cautious interpretation and further study given the observational design and potential residual confounding.

To evaluate the efficacy and safety of automated insulin delivery (AID) systems in very young children with type 1 diabetes (T1D). PubMed, Embase, Scopus, and Web of Science were searched until 10 October 2025. Inclusion criteria were randomized controlled trials (RCTs); T1D populations under 7 years old; comparing AID systems with standard care (SC). Primary efficacy endpoint was the percentage of time-in-range of 70-180 mg/dL (TIR) derived from continuous glucose monitoring (CGM), secondary outcomes included glycated haemoglobin (HbA1c), other CGM metrics, and insulin dose. Safety endpoints included severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA). Four RCTs involving 292 participants were included. The mean age was 4.70 years, with a mean T1D duration of 1.96 years. The study duration ranged from 8 to 16 weeks. Compared with SC, AID significantly improved TIR by mean difference (MD) +9.29% (95% confidence interval [CI]: 7.27-11.30, I2 = 70%, p < 0.001) accompanied by a favourable effect on HbA1c by MD -4 mmol/mol (-0.39%) (95% CI [-6 to -2] (-0.57 to -0.21), I2 = 82%, p < 0.001). A favourable decrease in time-above-range (TAR, >180 mg/dL; >250 mg/dL) and mean blood glucose were also observed in AID over SC (all p < 0.05). No significant differences were observed between AID and SC groups in time in hypoglycaemia, insulin dose, and risk of SH and DKA (all p > 0.05). AID systems may outperform SC in improving short-term glycaemic control (TIR, HbA1c, TAR) in very young children with T1D, without increasing time in hypoglycaemia, insulin dose, or risk of SH and DKA. These preliminary findings support the clinical potential of AID systems and highlight the need for longer term studies.

To investigate the associations between accelerometer-derived physical activity patterns-specifically the "weekend warrior" (WW) pattern versus regularly distributed activity-and the risk of incident microvascular complications among individuals with type 2 diabetes (T2D) and prediabetes. This prospective cohort study utilized data from the UK Biobank, analysing 12 923 adults with T2D and prediabetes who had accelerometer-measured data. Participants were classified into three groups: active WW (≥ 150 min/week; ≥ 50% of moderate-to-vigorous physical activity [MVPA] accumulated on 1-2 days), active regular (≥ 150 min/week but not meeting WW criteria), and inactive (< 150 min/week). Hazard ratio (HR) and 95% confidence interval (CI) for incident microvascular complications and their subtypes (diabetic kidney disease [DKD], neuropathy [DN], and retinopathy [DR]) were estimated using Cox proportional hazards models. Over a median follow-up of 7.88 years, 1235 incident microvascular complications were documented. Compared with the inactive group, both active patterns were associated with similarly reduced risks of microvascular complications (WW: HR 0.71 [95% CI 0.61-0.82]; regularly active: HR 0.63 [95% CI 0.52-0.77]). These protective associations extended consistently to DKD, DN and DR, with no statistically significant differences between WW and regularly active groups (all p > 0.05). Findings were robust across alternative MVPA thresholds, subgroup analyses, and sensitivity analyses. Concentrating recommended weekly MVPA within 1-2 days offers similar microvascular protection as regularly distributed activity among individuals with T2D and prediabetes, supporting flexible approaches for this high-risk population to achieve weekly activity goals.