Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy最新文献

Purpose: Substance use and sexual activity can impact the glycemic management and health of people living with type 1 diabetes (T1D), but data in pediatric populations are sparse. We set out to explore patient engagement and knowledge of the impacts on glycemia from substance use and sexual activity in a pediatric type 1 diabetes center.

Patients and methods: Surveys assessing rates and frequency of cannabis use, alcohol use, sexual activity, and participants' knowledge of their glycemic impacts were administered to participants ≥18 years old with type 1 diabetes between July 2024 and May 2025 at the Barbara Davis Center for Diabetes pediatric clinic. Respondents were classified by substance use (alcohol and/or cannabis) and sexual activity. Demographic and glycemic data were obtained from electronic medical records. Student's t-tests and chi-square tests were performed to compare between groups. Linear regression models were fit to compare HbA1c by cannabis use, adjusting for age, diabetes duration, non-Hispanic White race and ethnicity, and automated insulin delivery use.

Results: Of the 103 participants, 50 (48.5%) and 56 (54.4%) reported cannabis and alcohol use, respectively. Sexual activity was reported by 63 (61.2%) individuals. Cannabis users had a 0.8% higher HbA1c compared to non-users, even when controlling for confounders, and were less knowledgeable about its impact on glucose levels. Alcohol users were more knowledgeable about alcohol's impacts compared to non-users, especially concerning delayed hypoglycemia. Knowledge of goal HbA1c during pregnancy was low.

Conclusion: Substance use and sexual activity are common among emerging adults with T1D, though their knowledge around the impact on diabetes is limited. Consistent and comprehensive education on these topics should begin early as part of routine diabetes care in pediatric populations. Further research into the effect of cannabis on glucose levels and diabetes care is necessary.

Purpose: Cognitive flexibility, a core executive function, enables individuals to adapt to the behavioral demands of chronic disease management. Poor glycemic control, indicated by elevated glycated hemoglobin (HbA1c), may impair cognition, adherence, and quality of life in type 2 diabetes mellitus (T2DM). This study examined associations between glycemic control, cognitive flexibility, and HRQoL.

Methods: This cross-sectional study included 268 adults with T2DM recruited from a tertiary endocrinology clinic between March and September 2024. Eligible participants had been diagnosed within the past 10 years and maintained a stable regimen across their two most recent HbA1c assessments. Exclusion criteria included major comorbidities, psychiatric or neurological treatment, and pregnancy. HbA1c values were obtained from medical records. Cognitive flexibility was assessed using the Cognitive Flexibility Inventory (CFI), and health-related quality of life with the 12-Item Short Form Survey (SF-12). Group comparisons (adequate vs poor glycemic control), Pearson's correlations and multiple linear regression analyses adjusting for potential confounders were conducted using IBM SPSS Statistics. An a priori power analysis was performed using G*Power, confirming a sufficient sample size (power = 0.91).

Results: Of the 268 participants, 55.9% had poor glycemic control (HbA1c ≥ 7%). Compared with adequate control, those with poor control scored lower on CFI-Alternatives (p = 0.017, d = 0.51) and SF-12 mental component summary (p = 0.023, d = 0.56). Smaller but significant differences were found for CFI-Total (p = 0.037, d = 0.33) and SF-12 physical component summary (p = 0.042, d = 0.21). HbA1c correlated inversely with CFI-Alternatives (r = -0.228, p = 0.035), CFI-Total (r = -0.208, p = 0.038), and MCS-12 (r = -0.247, p = 0.022). These associations were clinically meaningful and remained significant in multiple linear regression analyses.

Conclusion: Poor glycemic control is associated with reduced cognitive flexibility and impaired HRQoL, particularly in the mental domain, among individuals with T2DM. The role of cognitive flexibility in treatment adherence warrants further investigation.

Background: Type 1 diabetes mellitus (T1DM) is a chronic disease mediated by autoimmunity, with complex and not fully elucidated pathogenesis. Mendelian randomization (MR) utilizes genetic instrumental variables to minimize confounding and reverse causation; however, individual MR studies are often limited by sample size and result heterogeneity.

Methods: Following PRISMA 2020 guidelines, we systematically searched PubMed, Web of Science, and other databases from 2014 to 2025, ultimately including 53 MR studies (covering 243 exposures). Random-effects models were used to pool effect sizes. Heterogeneity was quantified by Cochran's Q test and I² statistic. Bias was further controlled using Egger's regression and leave-one-out sensitivity analysis.

Results: This study integrated 53 MR studies (243 exposures) and identified key causal factors for T1DM.IL2RA (OR = 0.22, 95% CI: 0.17-0.27) and TYK2 (OR = 0.61, 95% CI: 0.54-0.69) showed significant protective effects, while IL6R (OR = 1.98, 95% CI: 1.48-2.65) was associated with increased risk. For metabolites, 3-phenylpropionic acid (OR = 0.90, 95% CI: 0.85-0.96) and cinnamoylglycine (OR = 0.89, 95% CI: 0.84-0.96) were protective, while trimethylamine N-oxide (TMAO; OR = 1.11, 95% CI: 1.02-1.20) increased risk. Among gut microbiota, Prevotella 9 (OR = 1.18, 95% CI: 1.08-1.30) was positively associated with risk, whereas Bifidobacterium (OR = 0.82, 95% CI: 0.71-0.95) showed a protective effect. Childhood obesity (OR = 1.32, 95% CI: 1.06-1.64) was also associated with increased T1DM risk. Overall heterogeneity was high (I² = 78.3%).

Conclusion: This study systematically mapped the multi-omics causal risk landscape of T1DM, providing important evidence for precision prevention and targeted intervention. These findings suggest that targeting immune pathways (particularly IL2RA and TYK2) and modulating gut microbiota composition may represent promising strategies for T1DM prevention. Future research should emphasize cross-ethnic validation and life-stage-specific intervention strategies.

Purpose: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. A high level of neutrophil-lymphocyte ratio (NLR) is an indicator of abnormal immune system activity which may serve as an effective potential inflammatory marker for identifying the risk of DN. This study aimed to investigate the relationship between neutrophil-lymphocyte ratio (NLR) and the incidence of DN in type 2 diabetes mellitus (T2DM) patients.

Patients and methods: DN incidence was defined as the time from baseline diabetes diagnosis to first DN occurrence (KDIGO CKD criteria). NLR's effect and interactions were evaluated using covariate-adjusted competing risks regression (death as competing event). The optimal NLR cut-point for DN prediction was determined by ROC analysis. The Fine and Gray subdistribution hazard model assessed NLR's effect on DN incidence, with subdistribution hazard ratios (sHR) validated via bootstrap sampling. The final sample consisted of the records of 220 individuals (median age 64 years (IQR: 55-72)) with T2DM with complete covariates information which were available for incidence analysis with NLR.

Results: Among 220 T2DM patients with complete covariates, 133 (60.45%) developed DN at 6 years, 20 (9.10%) were lost to competing events, and 67 remained DN-free. Median NLR was 2.4 (IQR: 1.8-3.3), positively correlating with urinary albumin-to-creatinine ratio and negatively with the estimated glomerular filtration rate (eGFR) (p<0.01). ROC analysis demonstrated diagnostic value for DN (AUC=0.772; 95% CI: 0.708, 0.836; p<0.01), with optimal cut-off at 3.02. NLR showed associations with DN in cause-specific (CSH=1.66; 95% CI: 1.13, 2.52) and FGR models (sHR=2.26; 95% CI: 1.72, 2.92). Bootstrap validation yielded consistent results (sHR= 2.36; 95% CI: 1.76, 3.02). Notably, NLR better predicts DN risk in older adults (>65 years) and those with well-controlled HbA1c (≤7.5%).

Conclusion: NLR shows promise for predicting DN incidence in Chinese patients, especially those >65 years or with good glycemic control.

Purpose: This study investigated the association between the serum uric acid-to-creatinine ratio (SUA/Cr) and sudomotor dysfunction in patients with type 2 diabetes mellitus.

Patients and methods: This was a single-center, inpatient, cross-sectional study. A total of 781 participants were classified into three tertiles based on their SUA/Cr. The electrochemical conductivity (ESC) of sweat obtained from the hands and feet was measured using SUDOSCAN to assess sudomotor function. Mean ESC values for the hands (HESC) and feet (FESC) were computed independently. Sudomotor dysfunction was defined as HESC or FESC ≤ 60 μS. Statistical analyses were performed using SPSS 25.0, involving one-way ANOVA, Kruskal-Wallis test, chi-square test, Spearman correlation coefficient, binary/multivariable logistic regression (with three adjusted models), and subgroup analysis, with statistical significance defined as p < 0.05.

Results: The prevalence of sudomotor dysfunction in the first, second, and third tertiles of SUA/Cr was 65.0%, 57.6%, and 48.9%, respectively. Patients with lower SUA/Cr levels exhibited a markedly increased risk of sudomotor dysfunction compared to those with higher SUA/Cr levels (p < 0.001). After adjusting for potential confounders, the association between decreased SUA/Cr ratio and sudomotor dysfunction risk remained significant (OR=1.646, 95% CI: 1.088-2.489, p = 0.018). Subgroup analyses by age, sex, glycated hemoglobin A1c, body mass index, and duration of diabetes confirmed the robustness of the relationship between SUA/Cr and the risk of diabetic peripheral neuropathy (all interactions p > 0.05).

Conclusion: The SUA/Cr ratio is independently associated with sudomotor dysfunction in patients with type 2 diabetes mellitus.

Background: The impact of basal metabolic rate (BMR) on non-alcoholic fatty liver disease (NAFLD) is still not fully understood, particularly regarding potential sex differences. We aimed to explore population-specific associations using data from health examinations, NHANES 2017-2020, and genome-wide association studies (GWASs).

Methods: 30,845 Chinese from health examinations and 5019 US adults from NHANES were analyzed. BMR was estimated using the Mifflin-St Jeor equation. Multivariable-adjusted logistic regression and restricted cubic splines (RCS) were applied. To determine the causality, a two-sample MR study was conducted among Europeans using GWASs data for BMR (IEU OpenGWAS) and NAFLD (FinnGen). Odds ratios (ORs) with 95% confidence intervals (CIs) were reported.

Results: In Chinese, ORs (95% CIs) for NAFLD across ascending quartile groups of BMR were 1 (reference), 1.17 (1.03-1.33), 1.83 (1.60-2.09), and 5.98 (4.92-7.28). The corresponding ORs (95% CIs) were 2.00 (1.67-2.39), 2.71 (2.24-3.29), and 4.91 (3.97-6.10) for males, and 1.64 (1.41-1.92), 1.93 (1.64-2.27), and 4.04 (3.41-4.81) for females. In the NHANES, weighted ORs (95% CIs) for NAFLD across quartile groups were 1 (reference), 1.84 (0.95-3.54), 4.98 (2.28-10.89), and 16.10 (6.69-38.72), with similar associations across sexes. Significant sex differences in BMR-NAFLD associations (P for interaction <0.05) were observed in the Chinese, but not in the US population. RCS revealed nonlinear dose-response relationships in both sexes within the Chinese population. Two-sample MR confirmed a causal effect with OR (95% CI) of 1.59 (1.24-2.03).

Conclusion: A higher BMR is an independent and causally relevant risk factor for NAFLD. The observed sex effect modification in the Chinese population suggests that population-specific management strategies may be warranted.

Objective: This study aimed to investigate the joint and independent associations of type 2 diabetes (T2DM) and body mass index (BMI) with arterial stiffness using carotid ultrasound-based measures.

Methods: This retrospective, matched cross-sectional study enrolled 255 participants, including people with T2DM (n=129) and Control group (diabetes-free, n=126). The control group was matched to the T2DM group based on age (±5 years), sex, and BMI category. People with T2DM were diagnosed according to World Health Organization criteria and classified into three BMI-based categories: lean (BMI<25 kg/m², n=48), overweight (BMI=25-29.9 kg/m², n=44) and obese (BMI≥30 kg/m², n=37). Carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were determined using sample images. Univariable and multivariable logistic regression models were used to evaluate the associations between BMI, T2DM and arterial stiffness, adjusted for potential confounders such as age, systolic blood pressure and lipid profiles. Interaction terms tested multiplicative effects.

Results: Compared to people with diabetes-free, those with T2DM had significantly greater IMT and PWV impairments (P<0.001). An increasing BMI category was associated with progressive IMT and PWV increase in people with T2DM (P<0.001). Multi-variable analysis revealed that BMI category had strong associations with carotid IMT (Standardize β 0.715, 95% CI: 113.4, 174.7) and PWV (Standardize β 0.544, 95% CI: 0.81, 1.73), indicating the progressive impact of BMI on arterial stiffness. No interaction was observed between T2DM and BMI (IMT: P-interaction=0.95; PWV: P-interaction=0.56), indicating independent effects.

Conclusion: This study demonstrates additive but non-synergistic effects of T2DM and BMI on arterial stiffness, with BMI driving the majority of vascular impairment. However, the cross-sectional design precludes causal inferences. The findings underscore the clinical relevance of weight management in people with T2DM.

Obesity, a global pandemic, has a profound adverse impact on health and quality of life (QoL). Therefore, bariatric surgery is the best way to lose weight in the long term and enhance QoL in Saudi Arabia. The data comprising 15 articles related to QoL following bariatric surgery among Saudi people were obtained through the search of databases: Google Scholar, PubMed, and ScienceDirect. The included studies provided data regarding the assessment of QoL via different tools, such as the impact of weight on quality of life (IWQOL-Lite), the Moorehead Ardelt quality of life questionnaire II (MA QoLQII), and the Short Form-36 questions (SF-36) in patients who had undergone bariatric procedures of any type. There was a significant improvement in parameters relevant to obesity, including weight, body mass index (BMI), triglycerides, blood pressure, hemoglobin A1c (HbA1C), and cholesterol, in post-bariatric participants. The weight decreased from 126.38 ± 24.97 kg to 81.41 ± 20.87 kg, and the BMI reduced from 45.78 ± 7.73 kg/m² to 30.56 ± 7.53 kg/m² in pre- and post-bariatric patients, respectively. The QoL score was higher after surgery, ie, 77.7 ± 15.3, compared to before treatment, ie, 58 ± 16.7. Increased weight loss and bariatric procedures contributed to better QoL among obese people in Saudi Arabia.

Purpose: Type 2 diabetes (T2D) is often associated with hypertension and dyslipidemia and is known to increase the risk for cardiovascular disease (CVD). A fixed-dose diabetes polypill, which can lower glycemia, blood pressure, and cholesterol, can improve treatment adherence in patients with T2D. This survey was conducted among healthcare professionals (HCPs) in India to assess the perceived T2D burden, clinical gaps, and intent to prescribe polypill to patients.

Methods: The study was conducted in two phases: Phase 1 quantitative online/in-person surveys to assess patient load, proportion of treatment-naïve patients, initiated/current treatment, patients achieving glycemic goals, and intent to prescribe polypill; and Phase 2 quantitative telephonic-aided online surveys to evaluate factors impacting treatment choice, validating polypill concept, and intention to prescribe.

Results: Phase 1 survey included 5,000 respondents (3,000 general practitioners [GPs], 1,500 diabetologists, 500 endocrinologists) and Phase 2 survey included 500 respondents (300 GPs, 150 diabetologists, 50 endocrinologists). Approximately 92% of HCPs indicated concern regarding treatment adherence for all risk factors. Treatment goals were reported to be achieved in 67%, 58%, and 52% patients for hyperglycemia, hypertension, and dyslipidemia, respectively. The most preferred pharmacological treatment approach was combination therapy (65%); around 84% of physicians preferred a fixed-dose therapy. Approximately, 79% HCPs believed that polypill demonstrated greater benefits compared to other products, and 86% of HCPs had high intention to prescribe polypill. The survey results indicated that most HCPs preferred fixed-dose therapy, and believed that a fixed-dose diabetes polypill could be beneficial in reducing T2D associated CVD risk factors in patients.

Conclusion: Most HCPs considered CVD risk management and adherence to medication as serious challenges and intended to prescribe an affordable and efficacious diabetes polypill to patients with T2D to lower CVD risk.

Objective: To examine the associations between platelet parameters and metabolic syndrome (MetS) and to explore their relationships with insulin resistance (IR).

Patients and methods: This cross-sectional study included approximately 570,000 adults who underwent health examinations at the Health Management Center of the First Affiliated Hospital of Wannan Medical College between 2017 and 2023. Demographic and behavioral data were collected using questionnaires, and relevant clinical measurements were obtained through physical examinations. Platelet parameters and metabolic indicators were measured using an automated analyzer. Restricted cubic spline (RCS) models and multivariable logistic regression analyses were used to assess the associations between platelet parameters and MetS. Bootstrap-based mediation analysis was applied to explore the statistical associations among platelet parameters, IR, and MetS.

Results: The prevalence of MetS was 19.5%. Platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) were all positively associated with MetS (all P < 0.001). After multivariable adjustment, PCT and PDW showed relatively stronger associations with MetS (PCT: Q4 vs Q1, aOR = 1.85, 95% CI: 1.81-1.89; PDW: Q4 vs Q1, aOR = 1.73, 95% CI: 1.69-1.76). Multivariable linear regression analysis showed that PDW was positively associated with IR assessed by the triglyceride-glucose index (TyG) (β = 0.150, 95% CI: 0.146-0.155). Within the analytical models of this study, PDW, IR, and MetS exhibited statistically significant associations.

Conclusion: Elevated platelet parameters were positively associated with MetS, with particularly pronounced associations observed for PCT and PDW. PDW was significantly associated with IR, and IR was in turn closely associated with MetS.