Diabetes, Obesity & Metabolism最新文献

Aims: The goal of this observational, single-cohort, pre-post study was to describe the association of tirzepatide with glycaemic control and weight loss in patients with type 2 diabetes (T2D) in a US commercially insured population.

Materials and methods: Using the Healthcare Integrated Research Database (HIRD®), members ≥18 years, diagnosed with T2D, initiating tirzepatide between 13 May 2022 and 31 January 2023, with ≥1 glycated haemoglobin (HbA1c) result around the index date and the end of the 6-month follow-up period were identified. Baseline demographics and antihyperglycaemic medication use and key outcomes (HbA1c and weight) at 6-month follow-up were assessed overall and in subgroups stratified by baseline glucagon-like peptide-1 (GLP-1) receptor agonist (RA) use and HbA1c (<7% and ≥7%) level.

Results: The cohort of 2247 identified patients was primarily non-Hispanic White, female (58%), 54 years old, 54% had GLP-1 RA at baseline, 59% had an HbA1c ≥7% at baseline and 61% had overweight/obesity. At 6-month follow-up, a majority of the cohort (69%) had an HbA1c <7%, which was higher (77%) in the GLP-1 RA naïve subgroup. Mean change in weight was: -6.3 kg for the overall cohort; -7.1 kg in patients with baseline HbA1c <7%; and -8.1 kg in the GLP-1 RA naïve subgroup.

Conclusion: In this observational, single-cohort study, at 6-month follow-up, patients with T2D initiating tirzepatide showed HbA1c and weight reductions; more pronounced HbA1c reductions occurred in GLP-1 RA naïve patients or those with baseline HbA1c ≥7%, while more weight loss was observed among GLP-1 RA naïve patients or those with baseline HbA1c <7%.

Aims: To investigate the underlying immune mechanisms during partial remission (PR) in type 1 diabetes (T1D) using single-cell RNA sequencing of peripheral blood mononuclear cells from healthy controls, newly diagnosed T1D patients, and those in the PR stage.

Materials and methods: We performed integrated analysis combining differential expression analysis, trajectory inference, cellular senescence evaluation and transcriptional network reconstruction to characterize monocyte heterogeneity and dynamic changes during disease progression. We identified five distinct monocyte subsets with unique molecular signatures and demonstrated their stage-specific alterations.

Results: The PR stage was characterized by persistent inflammatory responses, evidenced by the expansion of IL1B+ monocytes and sustained activation of TNF and IL6-STAT3 signalling pathways, while HDAC9+ populations showed significant reduction. Notably, the PR stage exhibited marked accumulation of senescent cells across monocyte subsets, demonstrated by elevated senescence-associated secretory phenotype scores and increased P21 expression. Trajectory analysis revealed altered developmental dynamics during PR, with distinct classical and non-classical monocyte branches. Transcriptional network analysis identified sustained activation of EGR1 and NFκB signalling throughout disease progression, particularly during PR.

Conclusion: These findings reveal previously unrecognized features of immune dysregulation during PR and provide potential therapeutic targets for T1D treatment.

Aims: To confirm the 'obesity paradox' in hospitalized populations and examine the heterogeneous effects of obesity on all-cause mortality risk.

Materials and methods: We included 5967 hospitalized patients from the Real-world Data of Cardiometabolic Protection (RED-CARPET) study (ChiCTR2000039901) in China. After 1:1 k-nearest neighbours matching, a causal forest model classified the population into four subgroups. Cox models were used to assess the association between obesity and all-cause mortality, with external validation in the Atherosclerosis Risk in Communities (ARIC) cohort.

Results: During a median follow-up of 63.8 months, 919 (15.4%) deaths occurred. A U-shaped association between body mass index (BMI) and all-cause mortality was observed, illustrating the 'obesity paradox', with the highest mortality rate (18.5%) observed in the normal weight group. Furthermore, 911 participants with obesity and 911 participants with normal weight, matched for homogeneity, were categorized into four subgroups using the causal forest model. In subgroup 3 (with good renal function, well-controlled blood glucose and favourable nutritional status), patients with obesity had a higher risk of all-cause mortality compared to those with normal weight (HR, 2.12; 95% CI, 1.06-4.22; p = 0.033). No significant association was observed in the other subgroups (p > 0.05). Similar results were verified in the ARIC study cohort.

Conclusions: The association between obesity and all-cause mortality is heterogeneous, as individuals with good renal function, well-controlled blood glucose and favourable nutritional status may experience a higher mortality risk. These findings emphasize the need for personalized management strategies in clinical practice to address the varying effects of obesity across different health conditions.

Aims: Proteinuria is a risk factor for end-stage kidney disease (ESKD) and cardiovascular disease (CVD) in patients with diabetes. However, the clinical implications of fluctuating proteinuria are unclear. We investigated the proteinuria burden and the risks of clinical outcomes in patients with diabetes using the Korean National Health Insurance Service database.

Materials and methods: This retrospective cohort study included patients with diabetes who participated in a national health screening between 2015 and 2016, with records of three previous health screenings. Each end-point was followed until 31 December 2022. The proteinuria burden (range: 0-4) was defined as the cumulative number of positive urine protein dipstick tests at each health screening. The outcomes included ESKD, CVD and all-cause mortality.

Results: Among 1 264 699 patients, 86.3%, 9.4%, 2.5%, 1.2% and 0.6% had proteinuria burdens of 0 to 4, respectively. The proteinuria burden and risks of clinical outcomes had dose-dependent associations; compared to proteinuria burden 0, the adjusted hazard ratio (95% confidence interval) of proteinuria burdens 1, 2, 3 and 4, respectively, were as follows: ESKD, 3.539 (3.326-3.766), 9.373 (8.816-9.965), 14.539 (13.652-15.484) and 19.704 (18.412-21.087); CVD, 1.247 (1.214-1.280), 1.530 (1.465-1.599), 1.815 (1.713-1.923) and 2.032 (1.883-2.192); and all-cause mortality, 1.335 (1.302-1.369), 1.703 (1.635-1.774), 1.959 (1.855-2.068) and 2.092 (1.945-2.250). Within the same proteinuria burdens, late-positive proteinuria was associated with worse outcomes than early-positive proteinuria.

Conclusions: The proteinuria burden was dose-dependently associated with clinical outcomes in patients with diabetes. Even a single positive dipstick test requires active management.

Objective: This study seeks to analyse the effect of the change and accumulation of residual cholesterol (RC) on the risk of diabetes.

Methods: The analysis included 5124 participants from the China Health and Retirement Longitudinal Study (CHARLS) and 2704 participants from the English Longitudinal Study of Ageing (ELSA), all of whom underwent two repeated RC measurements. Changes in the RC were assessed through K-means clustering analysis, and the cumulative RC was determined using the formula: by (RC_first + RC_second)/2 × (time interval between first and second assessments). We employed Cox proportional hazards regression models to analyse the effect of the changes and accumulation of RC on the development of diabetes.

Results: Individuals with consistently elevated RC levels (class 4) demonstrated a 1.98-fold increase in diabetes risk 95% confidence interval (CI: 1.38-2.84) in the CHARLS study and a 2.73-fold increase (95% CI: 1.69-4.38) in the ELSA study, compared with those with consistently low RC levels (class 1). Similarly, the risk of diabetes increased by 1.62 (95% CI: 1.21-2.18) times in CHARLS and 2.98 (95% CI: 1.81-4.88) folds in ELSA for participants with highest levels of cumulative RC relative to those with lowest levels of cumulative RC. Elevated cumulative RC remains a substantial risk factor for diabetes, irrespective of the cumulative LDL-C level.

Conclusions: Long-term exposure to high RC levels links to an elevated risk of diabetes. Therefore, maintaining optimal RC levels and continuously monitoring them may contribute to reducing the incidence of diabetes.

Aims: To evaluate the safety and effectiveness of iGlarLixi in people with type 2 diabetes mellitus (T2DM) in clinical practice in Mexico.

Materials and methods: This was a prospective, observational, multicentre study in adults with T2DM who were prescribed iGlarLixi in routine clinical practice in Mexico. The participants were followed for 24 ± 1 months. The primary endpoint included the incidence proportion, incidence rate of adverse drug reactions (ADRs), serious ADRs and the severity of suspected ADRs possibly related to iGlarLixi throughout the study.

Results: The study included 330 participants (mean ± SD age: 57.8 ± 11.9 years, weight: 77.1 ± 17.7 kg, duration of diabetes: 14.1 ± 9.9 years, and female: 55.5%). During the 24-month study, 59 participants (17.9%; 95% confidence interval [CI]: 13.9-22.4) reported 95 ADRs, with a mean of 0.164 events per participant-year. The most commonly reported ADRs were gastrointestinal disorders (11.2%), with nausea being the most frequent (7.3%). HbA1c decreased from 9.5% at baseline to 7.3% at the end of the study. Additionally, 51.7%, 64.6% and 86.3% of participants achieved the glycaemic target of HbA1c < 7%, FPG < 110 mg/dL and PPG < 180 mg/dL, respectively, at the end of the study. A significant decrease (p < 0.0001) in 7-point self-monitoring plasma or capillary blood glucose was observed from baseline to 3, 6, 12 and 24 months post iGlarLixi initiation.

Conclusions: iGlarLixi demonstrated a consistent safety profile aligned with findings from previous randomised controlled trials. The most common ADRs were gastrointestinal disorders that were generally tolerable. Over 50% of participants treated with iGlarLixi achieved their glycaemic targets.

Aims: To compare the risk of new-onset hyperglycaemia between inpatients treated versus non-treated with systemic glucocorticoids and identify factors associated with glucocorticoid-induced hyperglycaemia (GIH).

Materials and methods: We conducted a cohort study using electronic healthcare records of adults admitted to the Oxford University Hospitals between 2013 and 2023. We excluded patients with diabetes or prescribed systemic glucocorticoids before admission. The outcome was new-onset hyperglycaemia defined as a new glucose-lowering therapy, coded diagnosis of diabetes or random blood glucose ≥11.1 mmol/L. We used Poisson regression to estimate the incidence rate ratio (IRR) of new-onset hyperglycaemia during periods of exposure versus non-exposure to systemic glucocorticoids, adjusting for confounders. We used Poisson regression models to identify potential risk factors for GIH.

Results: Of 451 606 included patients, 17 258 (3.8%) received systemic glucocorticoids during admission. Totally 316 (1.8%) of patients exposed to systemic glucocorticoids developed new-onset hyperglycaemia versus 3430 (0.8%) non-exposed to systemic glucocorticoids. The multivariable-adjusted IRR (95% CI) for new-onset hyperglycaemia among exposed versus non-exposed was 2.15 (1.18-3.12). Covariates associated with GIH were: age (relative risk, 95% CI) 1.02 (1.01-1.03) per year, ethnicity (1.72 [1.04-2.86] Asian vs. White, 1.26 [1.05-2.70] other vs. White), weight 1.01 (1.01-1.03) per kg, indication (2.15 [1.21-3.52] autoimmune/inflammatory/infection vs. malignant, 2.11 [1.18-4.20] other vs. malignant) and cumulative glucocorticoid dose (1.23 [1.04-1.42], for 51-205 mg vs. >0-50 mg and 2.53 [1.89-3.40] for > 205 mg vs. >0-50 mg).

Conclusions: Treatment with systemic glucocorticoids versus no glucocorticoid treatment during hospitalisation more than doubles the risk of new-onset hyperglycaemia. Higher age, weight, cumulative glucocorticoid dose, non-White ethnicity and autoimmune/inflammatory conditions were independently associated with a higher risk of GIH.

Background: Emerging evidence has linked metabolic dysfunction-associated steatotic liver disease (MASLD) with accelerated cognitive decline and dementia. We aimed to investigate the associations of MASLD with volumes of total brain tissue and subcortical grey matter, and white matter microstructures in the UK Biobank.

Methods: This cross-sectional study included 29,195 individuals (aged 45-82 years) from the UK Biobank who undertook a magnetic resonance imaging (MRI) sub-study between 2014 and 2022. The brain MRI covers three modalities (T1, T2 FLAIR, and diffusion). Volumes of grey matter, subcortical grey matter structures, and regional cortex were derived from T1-weighted images. Fractional anisotropy (FA) and mean diffusivity (MD) were derived from diffusion tensor imaging (DTI) to assess global and tract-specific microstructure. MASLD was defined as the MRI-derived proton density fat fraction (MRI-PDFF) ≥5% and the presence of at least one cardiometabolic criterion. Data were analysed using multiple linear regression models.

Results: MASLD was significantly associated with smaller volumes of total grey matter and subcortical grey matter (p < 0.05) and reduced Alzheimer's disease (AD)-signature cortical thickness (multivariable-adjusted β = -0.04; 95% confidence interval [CI]: -0.07, -0.01). Having MASLD was associated with higher total white matter hyperintensity (WMH) volume (multivariable-adjusted β = 0.12; 95% CI: 0.10, 0.15). For white matter microstructure, MASLD was associated with increased global FA (multivariable-adjusted β = 0.05; 95% CI: 0.03, 0.08) and reduced global MD (multivariable-adjusted β = -0.04; 95% CI: -0.07, -0.01).

Conclusions: Brain morphology associated with MASLD is characterized by smaller subcortical grey matter volume and higher coherence but lower magnitudes of white matter microstructure.