This study investigates the association between type 2 diabetes mellitus and six psychosocial burdens (depressive symptoms, loneliness, and low levels of energy, life satisfaction, satisfaction with one’s activity level, and perceived social support) among older adults, using data from the population-based longitudinal study Gesundheit 65+ in Germany.
Research design and methods
Data were collected from June 2021 to April 2023 via a baseline survey and three follow-up waves, primarily using paper questionnaires. The present study included 12,514 observations across 3,547 participants aged 65 and older. The presence of type 2 diabetes in the last 12 months was self-reported. Psychosocial burdens were assessed using validated scales. Binomial and multinomial logistic regressions were conducted, adjusting for sex, age, education, physical activity, obesity, cardiovascular comorbidities and cancer.
Results
Type 2 diabetes was significantly associated with all examined psychosocial burdens in the unadjusted analysis. In the fully adjusted model, having type 2 diabetes increased the odds of experiencing depressive symptoms (OR 1.60, 95% CI 1.18 to 2.17), low energy (1.37, 95% CI 1.06 to 1.77), low/middle life satisfaction (1.41, 95% CI 1.15 to 1.73), loneliness (1.31, 95% CI 1.03 to 1.66) and neither satisfaction nor dissatisfaction with one’s activity level (1.38, 95% CI 1.11 to 1.72), whereas the association with perceived social support lost statistical significance. Sensitivity analysis confirmed the results. No significant interactions were found for sex, age group, or study wave.
Conclusions
Type 2 diabetes is associated with higher odds of different psychosocial challenges in older adults. These findings emphasize the need for integrated care models that routinely screen for and manage these conditions in persons with diabetes.
]]>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.
]]>Despite the known association between abdominal obesity (AO) and vitamin D deficiency, it remains unclear whether this combination is associated with higher mortality risk. We investigated whether the coexistence of AO and vitamin D deficiency elevates the risk of death.
Five thousand, five hundred twenty participants from the ELSA Study, aged ≥ 50 years, were followed for 6 years. AO was defined by waist circumference (> 102 cm for men and > 88 cm for women). Vitamin D levels, measured via serum 25-hydroxyvitamin D [25(OH)D] concentrations, were categorised as sufficient (≥ 50 nmol/L), insufficient (30–50 nmol/L), and deficient (< 30 nmol/L). At baseline, participants were classified according to AO (non-abdominal obesity [NAO] and AO) and 25(OH)D status (sufficiency [VDS], insufficiency [VDI], and deficiency [VDD]), creating six groups: NAO/VDS, NAO/VDI, NAO/VDD, AO/VDS, AO/VDI, and AO/VDD. Cox regression models adjusted for sociodemographic, behavioural, and clinical characteristics estimated mortality risk.
The NAO/VDI and NAO/VDD groups were associated with a 91% (HR = 1.91; 95% CI: 1.37–2.66) and 81% higher risk of death (HR = 1.81; 95% CI: 1.25–2.62), respectively. The AO/VDS and AO/VDI groups had a 47% (HR = 1.47; 95% CI: 1.02–2.14) and 50% higher mortality risk (HR = 1.50; 95% CI: 1.01–2.23), respectively, compared to the NAO/VDS group. The highest mortality risk was observed in the AO/VDD group (HR = 2.23; 95% CI: 1.50–3.33).
AO combined with 25(OH)D deficiency increases mortality risk in older adults. Early identification and management of these conditions could reduce this risk.
]]>This study aimed to investigate the associations between visceral obesity indices and the risk of mild cognitive impairment (MCI) in patients with diabetes and to identify the most valuable visceral obesity index to develop a risk assessment nomogram.
We explored the relationship between visceral obesity indices and MCI risk in patients with diabetes and developed a nomogram utilising a cohort of 1080 patients from Nanjing Drum Tower Hospital. MCI was diagnosed according to the criteria recommended by the National Institute on Aging-Alzheimer’s Association Workgroup. Logistic regression models were used to identify factors independently associated with MCI in the cohort. Furthermore, the nomogram was externally validated by a multicenter retrospective cohort (Cohort 2) and a prospective cohort with a follow-up period of up to 10 years (Cohort 3).
We identified a positive but non-linear dose–response relationship between visceral obesity indices and the risk of MCI in patients with diabetes. Compared with a body shape index (ABSI), visceral adiposity index (VAI), lipid accumulation product (LAP) and Chinese visceral adiposity index (CVAI), body roundness index (BRI) exhibited superior discriminative ability (AUC: 0.734, 95% CI: 0.703–0.764). The nomogram constructed from BRI, age, education and haemoglobin A1c (HbA1c) achieved an optimal AUC of 0.804 (95% CI: 0.777–0.830) in the internal validation cohort. The model exhibited consistent performance across external validations, yielding a discriminative AUC of 0.756 (95% CI: 0.722–0.790) in Cohort 2 and a 10-year predictive AUC of 0.762 (95% CI: 0.727–0.797) in Cohort 3.
Higher visceral obesity indices were associated with an increased risk of MCI in patients with diabetes. Assessment of visceral obesity may help identify patients with diabetes who are at a high risk of MCI.
]]>Lowering LDL cholesterol (LDL-C) decreases cardiovascular risk substantially in type 2 diabetes. Despite stricter LDL-cholesterol targets in the 2019 ESC/EAS dyslipidemia guidelines, target achievement in clinical practice remains insufficient. TEMD-2 is designed to evaluate LDL-cholesterol target attainment in Turkish patients with type 2 diabetes in the context of the updated 2019 ESC/EAS guidelines.
This multicenter cross-sectional study included adults with type 2 diabetes followed in 70 tertiary endocrine clinics across 36 cities between October 2022 and January 2023. Sociodemographic characteristics, comorbidities, lifestyle factors, complications, laboratory measurements, and lipid-lowering therapies were assessed using standardized questionnaires and clinical evaluations. LDL-C target was assigned according to cardiovascular risk categories. Independent predictors of goal attainment were identified using multivariable logistic regression.
Among 4956 adults with type 2 diabetes, 99.5% required statin therapy, whereas 37.1% were on treatment. Overall, 8.3% of the cohort achieved LDL-cholesterol targets, with attainment lowest in those at very high risk (5.8%). Target achievement among statin users was 57.7% in moderate-risk, 18.1% in high-risk, and 9.4% in very-high-risk patients. Individuals on target had lower body mass index, haemoglobin A1c (HbA1c), triglycerides, and a lower prevalence of microvascular complications. Statin therapy was the strongest positive predictor of success (odds ratio 2.39), while smoking, presence of neuropathy, nephropathy, female sex, older age, and higher HbA1c were associated with lower likelihood of achieving LDL-cholesterol goals. Therapeutic inertia was present in 87.2% of patients, defined as no intensification of lipid-lowering therapy despite LDL-cholesterol levels above target.
Three years after the implementation of the 2019 dyslipidemia guidelines, patients with type 2 diabetes remain far from achieving LDL-C targets, with fewer than one in ten reaching target levels. This shortfall is expected to translate into a growing burden of cardiovascular disease, morbidity, and premature mortality throughout the life course of individuals with diabetes.
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]]>We comprehensively investigated whether serum acylcarnitine levels are associated with and predict the decline of glomerular filtration rate (GFR) in type 2 diabetes.
Research design and methods
Two cohorts of patients with type 2 diabetes were investigated: a subset of the aggregate Gargano Mortality Study (aGMS, n=575; 9 years of median follow-up; mean age=60.9±9.8; mean diabetes duration=11.6±9.3) as a discovery set from Italy. A sample from the Joslin Kidney Study (JKS, n=252; 10 years of median follow-up; mean age=57.8±5.6; mean diabetes duration=14.2±7.6) was used as an independent validation set with different environmental and ethnic background for some associated metabolites in the aGMS.
Main outcome
estimated GFR (eGFR) change over time (mL/min/1.73 m2/year).
Results
Eleven out of the 40 acylcarnitines (by the AbsoluteIDQTM p180 Kit, BIOCRATES) were significantly associated with the rate of eGFR decline after Bonferroni correction. All 11 molecules were internally validated (p<0.05). Most of these associations survived the adjustment for several confounders, including age, sex, smoking habit, body mass index, glycated hemoglobin, disease duration, albumin excretion rate, triglycerides, low-density lipoprotein and statins treatment (p<0.05). Tiglylcarnitine and methylglutarylcarnitine, but not tetradecenoylcarnitine and hexadecenoylcarnitine, were also associated with eGFR decline in the JKS (p<0.05). Using multivariable least absolute shrinkage and selection operator regression analysis, methylglutarylcarnitine, hydroxyvalerylcarnitine, hexenoylcarnitine, decadienylcarnitine, dodecanedioylcarnitine, tetradecadienylcarnitine were independently associated with kidney function decline. The pairwise correlation among these ranged from –0.02 to 0.55. An acylcarnitine score comprising these six molecules improved discrimination (p<0.01) and reclassification (p<0.001) of two clinical prediction models of GFR decline in diabetes.
Conclusions
In patients with type 2 diabetes, four short, three medium and four long-chain acylcarnitines are associated with the rate of kidney function decline. Adding the acylcarnitine score to clinical prediction models improves the identification of individuals who are at greater risk of progression to kidney failure.
]]>To evaluate the association between semaglutide 2.4 mg and major adverse cardiovascular events (MACE) among adults with clinical atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity without diabetes in real-world clinical practice.
Adults aged ≥ 45 years with overweight/obesity and clinical ASCVD were identified from a United States database (2016–2024). Patients initiating semaglutide 2.4 mg were matched 1:2 with individuals not treated with semaglutide 2.4 mg through a propensity score model including > 70 demographic and clinical covariates. Primary outcomes were revised 3-point MACE (rMACE-3: myocardial infarction [MI], stroke, all-cause mortality) and revised 5-point MACE (rMACE-5: rMACE-3, heart failure [HF] hospitalisation, coronary revascularization). Secondary outcomes included 3-point MACE and 5-point MACE (replacing all-cause mortality with cardiovascular-related mortality) and HF composite outcomes; exploratory outcomes were incident type 2 diabetes (T2D), major adverse kidney events (MAKE) and major obesity-related adverse events (MORAE). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models.
The final sample comprised 38 308 patients with semaglutide 2.4 mg use propensity-score matched to 76 615 patients without. Over a mean follow-up of 8.6 months, semaglutide 2.4 mg significantly reduced the risk of rMACE-3 (HR: 0.55; 95% CI: 0.47–0.65), rMACE-5 (0.63; 0.56–0.71), MACE-3 (0.66; 0.56–0.78) and MACE-5 (0.69; 0.62–0.77). Semaglutide 2.4 mg also significantly reduced the risk of HF composite outcomes, T2D, MAKE and MORAE.
Semaglutide 2.4 mg was associated with a significantly reduced risk of MACE and other obesity-related outcomes, extending prior evidence of benefits to a broader clinical ASCVD population.
]]>To investigate how sleep features influence next-day diurnal glucose homeostasis and vice versa in free-living adults at risk of type 2 diabetes.
This observational repeated-measures study included 388 adults aged 25–65 years (50% women) with overweight or obesity (BMI ≥ 25.0–< 40.0 kg/m2). Sleep and glucose homeostasis were simultaneously assessed over 14 days using wrist-worn accelerometers and continuous glucose monitors. Linear mixed models evaluated day-level associations between sleep metrics—wake-up time, sleep period time (i.e., time from sleep onset to wake-up) and sleep efficiency ([total sleep time/sleep period time] × 100)—and diurnal glucose metrics, including mean glucose and its standard deviation (glycaemic variability).
We analysed 3942 valid person-days. Each 1% increase in sleep efficiency was associated with lower next-day mean glucose (B [95% CI] = −0.05 [−0.08, −0.01] mg/dL; p = 0.007). Each 1 h delay in wake-up time was linked to reduced next-day glucose variability (−0.24 [−0.38, −0.10] mg/dL; p = 0.001). Conversely, each 1 mg/dL increase in daytime mean glucose was associated with later wake-up time (0.008 [0.002, 0.014] h; p = 0.008), longer sleep period time (0.006 [0.000, 0.012] h; p = 0.039) and lower sleep efficiency (−0.05% [−0.08%, −0.01%] %; p = 0.005) the subsequent night. Each 1 mg/dL increase in glucose variability was associated with earlier wake-up time (−0.02 [−0.03, −0.01] h; p < 0.001).
This study provides evidence that sleep and glucose dynamics are temporally associated in free-living adults at risk of type 2 diabetes. These findings underscore the potential of combining sleep and glucose metrics to inform cardiometabolic risk prevention strategies.
]]>Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors are widely used for the treatment of type 2 diabetes, yet their downstream consequences in routine clinical practice remain incompletely characterized. We compared downstream treatment burden following initiation of GLP-1 receptor agonists versus SGLT2 inhibitors among adults with type 2 diabetes.
We conducted a retrospective, propensity score–matched cohort study using a multi-centre electronic health record network. Adults with type 2 diabetes who newly initiated a GLP-1 receptor agonist or an SGLT2 inhibitor between 1 January 2017 and 1 June 2025 were included. After 1:1 matching, approximately 164 000 patients were retained in each treatment group. Outcome-specific baseline-free cohorts with uniform washout periods were constructed, yielding sample sizes of approximately 124 000–164 000 per outcome. Primary outcomes were initiation of seven downstream medication classes. Secondary outcomes included gastrointestinal and nutritional diagnoses and health-care utilization.
Across all seven medication classes, downstream pharmacotherapy initiation occurred more frequently among GLP-1 initiators. The largest differences were observed for symptom-driven medications, including antidepressant, an absolute risk difference of 3.38% (95% CI −3.61 to −3.15) and a hazard ratio (HR) of 0.78 (95% CI 0.76–0.80), antiemetic, sedatives/hypnotics. Proton pump inhibitors, laxatives, histamine-2 receptor antagonists and antidiarrheal were also more frequently initiated, though differences were modest. Differences in secondary diagnoses were smaller. Gastroesophageal reflux disease and esophagitis were more common after GLP-1 initiation, whereas peptic ulcer disease and endoscopic procedures occurred more frequently among SGLT2 initiators. Nutrient deficiency and unspecified anaemia were more frequent following GLP-1 therapy. Overall health-care utilization was similar, except for inpatient acute care, which was more frequent among SGLT2 initiators.
Initiation of GLP-1 receptor agonists is associated with a downstream pharmacologic cascade characterized by increased use of symptom-driven medication without corresponding increases in health-care utilization. Medication initiation may provide a more sensitive measure of treatment burden than diagnostic codes or utilization metrics in routine diabetes care. To our knowledge, this study represents the largest multicentre real-world evaluation of downstream pharmacologic cascades following initiation of GLP-1 receptor agonists and SGLT2 inhibitors.
]]>Plasma glucose and HbA1c concentrations below the diagnostic threshold for diabetes have been achieved in people with type 2 diabetes (T2DM) in three clinical settings: with intensive weight-management programs that induce > 10–15 kg bodyweight loss, following bariatric surgery, and during treatment with highly effective glucose- and weight-lowering medications. The current consensus definition of T2DM remission excludes a status of absence of diabetes achieved with concomitant use of glucose- and weight-lowering medications. However, since these treatments can safely achieve HbA1c and plasma glucose concentrations lower than the ones currently used to define remission, we propose to consider a separate category of diabetes remission mainly achieved and maintained with pharmacological treatment. Our arguments are based on: (1) the similar endocrine mechanisms associated with bariatric surgery and use of GLP-1 receptor agonists or GIP/GLP-1 dual receptor agonists, (2) the lack of evidence that the effects of near-normoglycemic states achieved with lifestyle, surgery or glucose- and weight-lowering medications on long-term complications differ and (3) the frequent use of these medications in conjunction with both lifestyle interventions and following bariatric surgery. With this proposal, we aim to invite further discussion towards expanding the current narrow definition of T2D remission to include remission during treatment with newer highly effective glucose- and weight-lowering medications.
]]>South Asians exhibit an unfavourable metabolic phenotype characterized by visceral obesity, insulin resistance and dyslipidemia. While various hormones play a critical role in regulating postprandial energy metabolism, it remains unclear whether they respond differently to food intake. We aimed to compare the meal-induced excursion of incretin hormones (GLP-1 and GIP) and glucagon between South Asians and Europids.
Forty nine young, lean South Asian (n = 24), and Europid (n = 25) males and females underwent an extended (up to 240 min) mixed meal tolerance test (MMTT). At seven time points circulating incretins (active and total GLP-1 and GIP), glucagon, and parameters related to glucose (i.e., glucose, insulin) and lipid metabolism were measured.
In response to the MMTT, Europids generally exhibited a single peak in glucose levels at t = 30 min, while South Asians tended to display a biphasic glucose response, with peaks at t = 30 and t = 90 min. Among South Asian males, this was accompanied by an increased insulin response, characterized by elevated levels at the corresponding glucose peaks. South Asian females, however, demonstrated a marked drop in circulating glucagon at t = 90 min, and biphasic excursions of total and active GLP-1 and GIP (t = 30 and t = 120 min). Postprandial lipid excursions did not differ between ethnicities.
In contrast to a monophasic glucose response to the MMTT of Europids, South Asians tended to exhibit a biphasic glucose response, with sex-specific hormonal patterns, suggesting altered incretin and insulin dynamics despite similar postprandial lipid excursions.
ClinicalTrials.gov (NCT05829018; registration date: 25-04-2023)
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