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

Objective: This study aims to investigate the efficacy of an extended oral glucose tolerance test (OGTT) incorporating 1- and 3-h time points in detecting early, heterogeneous glycemic phenotypes in polycystic ovary syndrome (PCOS).

Methods: In this cross-sectional study, 103 treatment-naive patients with PCOS underwent a 75-g OGTT with measurements of glucose and insulin taken at 0, 1, 2, and 3 h. Participants were stratified into four groups: normal control, isolated 1-h glucose elevation (1-h plasma glucose [PG] ≥ 8.6 mmol/L), isolated 3-h glucose elevation (3-h PG > 6.1 mmol/L), and dysglycemia defined by conventional criteria. Comprehensive metabolic and endocrine profiles were evaluated and compared.

Results: Two distinct early glycemic phenotypes were identified: isolated 1-h glucose elevation (13.6%, 14/103) and isolated 3-h glucose elevation (20.4%, 21/103). The isolated 3-h elevation group exhibited an intermediate phenotype characterized by significant central adiposity, hyperandrogenism, and menstrual irregularities, despite systemic insulin resistance (IR) levels comparable to those of the normoglycemic group. Conversely, the isolated 1-h elevation group exhibited transient hyperinsulinemic hyperglycemia and elevated low-density lipoprotein cholesterol (LDL-C) levels. Both phenotypes were undetected by standard glycemic criteria.

Conclusion: An extended OGTT reveals two prevalent yet distinct early glycemic phenotypes in PCOS, suggesting heterogeneous pathophysiological pathways that may inform dynamic, phenotype-stratified assessment for risk stratification and targeted intervention. However, clinical implementation requires validation through prospective studies.

The general recommendation for hypoglycemia treatment is 15 grams (g) of simple carbohydrates, with re-check in 15 minutes. This oral hypoglycemia treatment is universally applied without consideration of the type of diabetes or the cause of hypoglycemia. These recommendations were only based on two small-sized studies of intravenous insulin-induced hypoglycemia in adults living with type 1 diabetes mellitus (T1D). We aimed to determine, in people living with T1D, which oral carbohydrate treatments attain >50% non-severe hypoglycemia (glucose 3.0 to 3.9 mmol/L) resolution at time of first glucose re-check. Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials were searched for full-text studies of oral treatment for non-severe hypoglycemia in T1D. Two authors screened the results and extracted data. Amongst the four studies of multiple daily insulin injections or non-closed-loop insulin pumps, >50% hypoglycemia resolution at first re-check was only observed in two studies: exercise-induced hypoglycemia study with 20 grams of glucose treatment attaining 60% hypoglycemia resolution at 15 minutes; real-life patient recorded study with 0.2 grams per kilogram body weight (g/kg) or 0.3 g/kg or 15 g glucose tablet treatment attaining 61%, 71%, and 63% hypoglycemia resolution at 10 minutes, respectively. Two of the three studies of closed-loop insulin pumps achieved >50% hypoglycemia resolution at first re-check: 16 grams of glucose tablets at 20 minutes attained 58% hypoglycemia resolution; 10 to 30 g of sucrose attained 79 to 100% hypoglycemia resolution at 15 minutes. The optimal quantity of oral carbohydrate treatments for T1D required to attain hypoglycemia resolution at first glucose re-check varies based on cause of hypoglycemia and type of insulin management.Systematic Review Registration: Prospero registration number: CRD420251033695; no amendments. Study protocol and literature search strategies are available from the authors upon request.

Purpose: This prospective cohort study with a nested case-control analysis aimed to identify gut microbial taxa associated with type 2 diabetes in older Chinese adults and to examine whether dietary balance influences diabetes-related microbial features.

Patients and methods: This study included 507 community-dwelling adults aged 65 years and older from the Surveillance and Management of Disability and Cognitive Impairment in Older Adults (SUM-DCI) cohort. Fecal samples were collected at baseline and analyzed using 16S ribosomal RNA gene sequencing to characterize gut microbial composition. Diabetes status was defined by fasting plasma glucose concentration ≥7.0 mmol/L or a self-reported physician diagnosis. A nested case-control study of 93 individuals (31 cases) was conducted within the baseline non-diabetic population to evaluate prospective associations. Metastats and Multivariate Association with Linear Models (MaAsLin) were used to identify diabetes-associated microbial taxa. Dietary intake was assessed using a self-reporting food frequency questionnaire, dietary balance was quantified using the Chinese Dietary Balance Index-22. Multivariable logistic regression was used to evaluate associations between dietary balance and gut microbial abundance.

Results: Roseburia abundance was significantly lower in individuals with type 2 diabetes (FDR -adjusted P < 0.05). Higher baseline Roseburia abundance was associated with a lower risk of incident diabetes (OR: 0.225, 95% CI: 0.115-0.818, P<0.05). Low soybean intake was independently associated with reduced Roseburia abundance (OR: 0.61, 95% CI: 0.39-0.94, P<0.05), whereas overall dietary imbalance scores were not significantly related.

Conclusion: Reduced Roseburia abundance is linked to both prevalent and future incident type 2 diabetes among older adults. Low soybean intake may contribute to this microbial depletion, suggesting a potential mechanism by which dietary habits influence diabetes risk through modulation of the gut microbiota.

Purpose: Action of metformin, the preferred pharmacologic treatment for type 2 diabetes (T2D), remains incompletely understood. Metformin induces an iron starvation response in yeast, suggesting tissue iron might be related to metformin responsiveness. We therefore examined the effects of different levels of tissue iron on metformin action.

Subjects and methods: We examined glycemic responses to metformin and effects on downstream targets of metformin in mice on diabetogenic diets with different iron contents and performed a retrospective study of metformin effectiveness as a function of serum ferritin, a reliable marker of tissue iron, in human patients after initiation of metformin therapy.

Results: Metformin provided the most glycemic benefit to mice on the normal-iron diet, compared to high or low iron. The low-iron diet itself provided glycemic benefit, and on low iron, metformin provided no additional benefit. These results were parallelled by effects of dietary iron on downstream targets of metformin action, including AMP-dependent kinase and glycerol-3-phosphate dehydrogenase 2. Increased protein modification by O-linked N-acetylglucosamine (O-GlcNAc) mimicked lower iron levels, abrogated the effect of high iron, and resulted in smaller relative metformin responses on glycemia and downstream reporters. Humans with higher or lower levels of the iron biomarker ferritin also exhibited a decreased HbA1c response to metformin.

Conclusion: Dietary iron and serum ferritin predict the glycemic response to metformin in mouse models and humans with T2D. Protein O-GlcNAcylation has effects paralleling low iron and may play a role in mediating these interactions.

Background and purpose: Diabetic retinopathy (DR) is one of the common and serious microvascular complications of diabetes mellitus (DM), DR carries a high risk of blindness and significantly impairs patients' quality of life. This study aims to systematically evaluate the efficacy and safety of Chinese Medicine Eye Nebulization (CMEN) therapy for DR and further explore its mechanisms of action.

Patients and methods: As a single-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial, this study will enroll 80 patients with non-proliferative diabetic retinopathy (NPDR) at stage II, characterized by the TCM syndrome of Qi-Yin deficiency with blood stasis. Participants will be randomized in a 1:1 ratio to receive either CMEN therapy (n=40) or placebo aerosol therapy (n=40). The intervention will be administered continuously for 2 weeks. The primary outcome measures include the improvement of clinical symptoms (blurred vision, dry eyes) and quality of life, assessed using the "Xiaoke Eye Disease Primary Symptom Score Scale", the Ocular Surface Disease Index (OSDI) Dry Eye Score Scale, and the Diabetes Mellitus Quality of Life Scale (DMQLS) Chinese Version for type 2 diabetes. Secondary outcomes encompass changes in visual acuity, fall risk assessment, levels of inflammatory and oxidative stress biomarkers (VEGFA, TNF-α, IL-6, IL-8, CCL2, MDA, SOD, GSH), and the progression of fundus lesions evaluated by optical coherence tomography (OCT). Assessments will be conducted at baseline, the end of the 2-week treatment period, and the end of the 4-week follow-up period. Multivariate analysis of variance (MANOVA) will be employed to examine the associations between different groups, time points, and group-time interactions.

Discussion: This study represents the pioneering application of CMEN therapy in the treatment of DR, with a specific focus on its effects on core clinical symptoms (blurred vision and dry eyes), quality of life, as well as inflammatory and oxidative stress biomarkers in DR patients.

Purpose: Given that obesity and type 2 diabetes mellitus (T2DM) share complicated pathophysiological mechanisms, this study aimed to establish a diagnostic model for the two diseases using feature selection from fatty acids, amino acids, and clinical characteristics.

Methods: This prospective study included 81 obese patients, 25 T2DM patients and 33 healthy controls. Amino acids and fatty acids in serum were tested using LC-MS/MS method. Anthropometric and laboratory measurements were recorded. All samples were split into a training set and a test set (7/3 ratio).

Results: Total 54 variables were significantly different between obesity, T2DM and control groups (p-value < 0.05). In uni-variable logistic regression analysis, 44 variables were significantly associated with disease diagnosis. LASSO, RFE and RF algorithms jointly selected 7 optimal variables (Ala, His, Gln, IL-10, age, FBG, and AHR). The support vector machine (SVM) diagnostic model based on the 7 variables showed robust performance in both the training set (AUC = 0.998) and the validation set (AUC = 0.958). Obesity or T2DM patients had significantly increased Ala (p-value < 0.01) but decreased Gln, His and IL-10 (p-value < 0.01) in serum compared to healthy controls. Gln and His levels were positively correlated with IL-10 level (Cor = 0.46, 0.48, p-value < 0.001).

Conclusion: This study developed a 7 feature-based diagnostic model for obesity and T2DM and suggested that Ala, His, Gln, and IL-10 were involved in the common mechanisms and might be potential therapeutic targets.

Purpose: The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including liraglutide and semaglutide, has expanded rapidly due to their effectiveness in weight management and glycemic control. Rising public interest, off-label cosmetic use, and prescription-free requests highlight the critical role of community pharmacists in ensuring appropriate patient counselling, safe dispensing, and rational use of these agents. This study aimed to assess the knowledge, attitudes, and practices of community pharmacists regarding GLP-1 RAs in Türkiye.

Patients and methods: A cross-sectional survey was conducted among 500 community pharmacists in Türkiye between January and April 2025. Data were collected using a structured, literature-based questionnaire covering sociodemographic characteristics, attitudes, knowledge, and professional practices. Knowledge was evaluated using a 25-item scoring system. Statistical analyses included descriptive statistics, chi-square tests, independent samples t-tests, and one-way ANOVA, with significance set at p<0.05.

Results: Requests for semaglutide and liraglutide were primarily for weight loss purposes (82.6% and 79.4%, respectively), and these agents were often sought without a prescription (over 60%) or medical recommendation (over 35%). The mean knowledge score was 15.8±4.3. Differences were observed across gender, professional experience, and pharmacy setting (p<0.05), with higher scores among female pharmacists, those with more than 16 years of experience, and those working in shopping mall pharmacies. Although most respondents correctly identified both medications as GLP-1 RAs (85.6% for semaglutide; 83.6% for liraglutide), gaps remained in regulatory awareness and consistency of routine counselling. A substantial proportion perceived misuse, with over 60% reporting concerns for both medications.

Conclusion: Community pharmacists demonstrate moderate knowledge and active involvement in counselling for GLP-1 RAs; however, gaps persist in addressing off-label demand and safety-related patient guidance. Targeted pharmacist education and clearer regulatory communication may enhance safe and evidence-based use of GLP-1 RAs.

Purpose: This study aimed to investigate the prevalence, predictors, and clinical consequences of delayed insulin initiation in patients with type-2 diabetes mellitus in a tertiary care setting.

Patients and methods: A retrospective cohort study was conducted in 973 adults with type-2 diabetes mellitus with initiated insulin therapy between January 1, 2004 and December 31, 2023 at a university hospital in southern Thailand. Delayed insulin initiation was defined as insulin initiation ≥6 months after documented treatment failure (glycated hemoglobin ≥7% on oral agents), reflecting clinical inertia. Logistic regression was used to identify the predictors of delay. Time-to-event analyses and restricted mean survival time were used to compare diabetes-related complications between groups.

Results: Delayed insulin initiation occurred in 35% of the patients. Independent predictors included higher body mass index, longer duration of diabetes, biguanide use, and diuretic use, whereas dipeptidyl peptidase-4 inhibitor use was associated with timely initiation. Although no significant differences were observed in overall macrovascular or microvascular complication rates, delayed initiation was significantly associated with increased amputation risk (hazard ratio: 2.33; 95% confidence interval: 1.07-5.07) and earlier onset of microvascular complications within the 10-15-year window (restricted mean survival time difference: -0.56 years, p=0.043).

Conclusion: Delayed insulin initiation is common and linked to identifiable clinical characteristics and adverse outcomes, including increased risk of amputation and earlier microvascular complications. Prioritizing timely insulin initiation is essential to reduce long-term complications and preserve limb health, particularly in high-risk individuals.

Aim: Obesity is common in women with polycystic ovary syndrome (PCOS) and can exacerbate PCOS symptoms. Although Acupoint catgut embedding (ACE) is frequently used to treat the clinical symptoms of simple obesity, it is unclear how it will affect obesity associated with PCOS. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate the effectiveness of ACE in treating obesity in women with PCOS.

Methods: We searched databases from inception to January 8, 2025. Two independent reviewers extracted data and assessed the risk of bias. All meta-analyses used random effects models, and the GRADE approach was used to assess the certainty of the evidence.

Results: We included 25 RCTs (1,663 participants). Based on usual care, compared to blank treatment, ACE probably reduces body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC), and may enable a greater proportion of patients to achieve a weight loss no less than 5% (relative risk [RR] 1.33, 95% CI 1.15 to 1.55) and may reduce triglycerides (TG). Furthermore, when compared to active comparators, ACE probably enables a greater proportion of patients to achieve a weight loss no less than 5% (RR 1.40, 95% CI 1.11 to 1.76) and reduces WC and may also reduce BMI and TG. All effects were supported by low to moderate certainty evidence.

Conclusion: When compared to blank treatment, on the basis of usual care, ACE for obesity associated with PCOS may improve obesity-related outcomes. When compared to active comparators, it may have comparable or greater therapeutic efficacy and fewer adverse events. Such improvements in obesity-related indicators may help alleviate metabolic and reproductive symptoms in women with PCOS. As all included trials were conducted in China, further high-quality studies in diverse populations are needed to confirm the generalizability of these findings.

Objective: To evaluate the association between serum vitamin D3 levels in patients with type two diabetes mellitus (T2DM) and diabetic macular edema (DME) taking into consideration other factors such as demographic, metabolic, and clinical confounders.

Methods: This retrospective case-control study included patients with T2DM attending a tertiary ophthalmology clinic. Cases were patients with clinical and OCT-confirmed DME. Controls had no DME. Patients with severe NPDR or higher stage were excluded. The study involved collecting several variables including age, sex, diabetes duration, HbA1c, BMI, smoking status, vitamin D3 levels, comorbidities, and vitamin D supplementation. Vitamin D3 was categorized into three groups: <10, 10-30, and >30 ng/mL. Logistic regression was used to identify independent predictors of DME.

Results: A total of 332 participants were analyzed. A total of 184 control patients were compared to 148 DME patients. DME patients had significantly longer diabetes duration (12.91 y vs 17.21 y, p < 0.001 for Non-DME and DME groups respectively) and lower vitamin D3 levels (25.16 ng/mL vs 16.71 ng/mL, p < 0.001 for non DME and DME groups respectively). Vitamin D3 deficiency (<10 ng/mL) was independently associated with increased odds of DME, whereas vitamin D3 sufficiency (>30 ng/mL) was protective. Cigarette smoking, paradoxically, was found to be associated with lower odds for DME.

Conclusion: Vitamin D3 deficiency is associated with increased odds of DME. Interpretation should be cautious due to methodological limitations, including potential selection bias, unmeasured confounding, and lack of adjustment for diabetic retinopathy severity. Further research is required to explore further cause-effect relationship and effect of supplementation on the disease itself and response to treatment.