Acta Diabetologica最新文献

Background and objective: Diabetic complications can significantly affect the quality of life and prognosis of patients with diabetes. This study employed a systematic approach to elucidate the causal relationship between serum metabolites and six prevalent diabetic complications using a Mendelian randomization (MR) strategy.

Methods: Serum metabolite data were obtained from genome-wide association studies, and data on six diabetic complications were acquired from the FinnGen consortium. A two-sample MR approach was used to investigate the association between serum metabolites and common diabetic complications. Reverse MR analysis was conducted to investigate potential causal relationships between diabetic complications and serum metabolite levels. Sensitivity analyses were performed to evaluate the robustness of our findings. Analyses included inverse-variance-weighted, MR-Egger, linkage disequilibrium score regression, and colocalization approaches.

Results: We identified 81 causal associations, highlighting the significance of serum metabolites in the context of diabetic complications. The results identified significant causal associations: Bilirubin degradation products were inversely linked to diabetic retinopathy, while androstane sulfate and N-succinyl-phenylalanine increased the risk of retinopathy. Caffeine metabolites and adenosine 5'-monophosphate-to-citrate ratios were positively associated with nephropathy. Reverse MR analysis confirmed unidirectional causality, and sensitivity tests ruled out pleiotropy. Colocalization analyses highlighted shared genetic loci, such as rs2991970, between metabolites and hypoglycemia.

Conclusion: These findings elucidate metabolite-specific pathways underlying diabetic complications and propose novel biomarkers for risk stratification. The limitations of this study include its European-centric nature and the lack of stratified covariates. This study highlights the value of integrating genetic and metabolomic data to enhance precision medicine in diabetes management.

Purpose: Characteristics defining "early" type 2 diabetes (T2D) are unclear, and type and timing of treatment intensification with glucose-lowering drugs (GLD) in these patients are understudied.

Methods: Within the AMD Annals Initiative, we evaluated the prevalence and clinical characteristics of early T2D subjects, evaluated by diabetologists and defined according to a recent Delphi Consensus. Patient characteristics of early T2D subjects were compared to those of non-early patients. We also explored the time and mode of first intensification in a longitudinal cohort from 2010 to 2023.

Results: Overall, 127,456 people were seen in 2023, of whom 10,700 (8.39%) showed an early phenotype. Early patients were younger, more often females, had lower HbA1c, used less cardiovascular-related drugs, and had a lower prevalence of cardiovascular disease.

Conclusion: In real life, T2D could be considered as early in only ~ 8% of people. Among them, less than 10% received treatment intensification during the first year of observation, although the timing of the introduction of add-on GLD improved during time and drugs with cardiovascular benefit were often chosen as second-line GLD. In longitudinal analysis, of 42,786 early patients initially treated with metformin, 9.37% were prescribed an add-on treatment during 12 months, more frequently represented by SGLT2i, followed by GLP1-RAs and DPP4i. Mean level of HbA1c at treatment intensification improved over time, suggesting an encouraging trend through a proactive approach.

Background: Gestational diabetes mellitus (GDM) is a common metabolic disorder that creates considerable risks regarding both maternal and fetal health. Conventional screening approaches for GDM which are typically performed in the late second trimester; frequently miss an important window for early intervention.

Methods: This meta-analysis seeks to evaluate the diagnostic accuracy of first-trimester maternal serum biomarkers, particularly pregnancy-associated plasma protein-A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG), in the prediction of GDM. This systematic review of observational studies was conducted to assess PAPP-A and/or β-hCG levels during the first trimester, examining their correlation with the subsequent diagnosis of GDM. This meta-analysis collected data from numerous studies to evaluate sensitivity, specificity, likelihood ratios and diagnostic odds ratios; alongside with developing summary receiver operating characteristic (sROC) curves.

Results: This diagnostic meta-analysis assessed 23 studies encompassing first-trimester PAPP-A and β-hCG measurements with regards to early prediction of GDM. The overall pooled sensitivity and specificity were found to be 63% (95% CI: 53-73%) and 70% (95% CI: 61-78%), alongside an AUC of 0.72 (95% CI: 0.68-0.76). Substantial heterogeneity was observed regarding both sensitivity and specificity (I² >95%). Unaccompanied PAPP-A showed a sensitivity of 67% (95% CI: 55-77%) and specificity of 66% (95% CI: 54-76%) with AUC of 0.71, while β-hCG alone exhibited low sensitivity of 29% (95% CI: 7-69%) despite a high specificity of 87% (95% CI: 64-96%) with its AUC found to be 0.71. Fagan's analysis revealed modest clinical impact; which was found to be raising post-test probability from 20% to ~ 39% after a positive result. Deek's tests suggested no major publication bias (p = 0.45 for overall, 0.41 for PAPP-A, 0.08 for β-hCG). Subgroup analyses revealed higher sensitivity levels in studies utilizing ADA criteria and in studies with smaller samples, while those with cohort designs generated more conservative estimates upon comparison with their case-control counterparts.

Conclusion: First-trimester PAPP-A and β-hCG are found to express modest diagnostic accuracy and therefore are best considered as adjuncts to early risk stratification regarding GDM. PAPP-A, as stand-alone, provides balanced though moderate levels of sensitivity and specificity, whereas β-hCG shows high specificity levels but very low sensitivity level; thus, limiting its independent predictive value. Neither biomarker is found to be sufficient as a stand-alone diagnostic tool, but both may contribute to comprehensive risk models which might inform timely intervention. Future research should emphasize standardized methodologies and validation in large, diverse populations in order to improve clinical applicability.

Background: Excess weight is a progressive metabolic epidemic, and inflammation plays an important role in the progression of disease. Insulin resistance (IR) is an important feature of obesity, but it does not reflect systemic inflammation. Currently, there is a lack of effective clinical tools for early risk stratification and intervention in physically active people.

Methods: This was a prospective cohort of 72,262 overweight but physically active persons in the UK Biobank. The TyG was combined with hsCRP, waist circumference (WC), or body mass index (BMI) as indices of IR. Adjusted Cox regression, interaction tests, restricted cubic splines (RCS) analysis, Kaplan-Meier analysis, and Harrell's C-index were used to examine the relations and time-dependent predictive power.

Results: During 12.7 years of follow-up, 1,477 participants developed metabolic dysfunction-associated fatty liver disease (MAFLD). RCS analysis suggested TyG-hsCRP had a nonlinear positive correlations with all-cause mortality. Compared to the lowest quartile group, the corrected hazard ratio (HR) (95% confidence interval [CI]) of new-onset MAFLD in maximum quartile groups for TyG-hsCRP was 1.94(1.62-2.32), for TyG-WC was 1.78(1.44-2.18), for TyG-BMI was 1.36(1.12-1.65), and for TyG was 1.41(1.15-1.72). The relation between C-index of TyG-hsCRP and MAFLD was higher than that of other TyG indices. Similar results were observed in all-cause mortality.

Conclusion: TyG-hsCRP is superior to other indices for identifying risk of MAFLD and all-cause mortality in overweight but physically active people. Our findings suggest the importance of inflammatory metabolism and provide evidence for effectively early anti-inflammatory treatments.

Background: Reduced angiogenesis is a key factor in impaired healing diabetic foot ulcers. It is critical to identifying the relevant genes that regulate angiogenesis or the relevant mechanisms that accelerate angiogenesis, which is essential for the treatment of Diabetic foot ulcers (DFU).

Methods: Direct targeting of miR-125a-5p to Glutathione S-Transferase M5 (GSTM5) was demonstrated by dual luciferase assays. MiR-125a-5p and GSTM5 were induced or silenced by HGM in endothelial cells in vitro, and the results were compared with a blank control to determine the mechanism of miR-125a-5p and GSTM5 expression levels on DFU.

Results: Initial analysis revealed distinct expression patterns of miR-125a-5p and GSTM5 between acute and chronic DFU patients. Their regulatory roles were investigated by comparing differential expression profiles in these two patient groups. We found that low expression of both in chronic DFU patients was positively correlated with changes in angiogenic markers. Inhibition of miR-125a-5p and GSTM5 in endothelial cells in vitro yielded the same results, demonstrating the promote angiogenesis of their expression on angiogenesis.

Conclusion: MiR-125a-5p promotes normal angiogenesis in diabetic foot ulcers by targeting GSTM5.

Introduction and objective: Macronutrient sequence has been proposed as a practical strategy to improve postprandial glycemia in individuals with type 2 diabetes (T2D). However, current evidence remains inconclusive. This meta-analysis aims to provide an updated evaluation of the impact of a carbohydrate-last (CL) strategy, compared to carbohydrate-first or unordered (CF) intake, on metabolic parameters in adults with T2D.

Methods: A systematic search was conducted in PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) evaluating nutrient intake order in T2D. Outcomes were analyzed using mean difference (MD) with 95% confidence intervals (CI) under a random-effects model. Heterogeneity was assessed using Cochrane's Q test and I² statistics. Analyses were conducted using R, version 4.4.2.

Results: Seventeen studies involving 389 participants were included, with 114 (29%) in a parallel design and 192 (49%) in a crossover design receiving CL. In the pooled analysis, the CL group had significantly lower postprandial glucose at 60 min (MD: -42.73 mg/dL; 95% CI: -55.51, -29.96; p < 0.01) and 120 min (MD: -13.00 mg/dL; 95% CI: -21.07, -4.94; p < 0.01), higher postprandial glucagon-like peptide-1 (GLP-1) levels (MD: 8.21 pmol/L; 95% CI: 2.34, 14.09; p < 0.01), delayed gastric emptying half-time (MD: 28.14 min; 95% CI: 16.06, 40.23; p < 0.01), and reduced glycated hemoglobin (HbA1c) at follow-up (MD: -0.16%; 95% CI: -0.31, -0.01; p = 0.04).

Conclusion: Carbohydrate-last eating pattern has been shown to improve postprandial glycemia, enhance GLP-1 secretion, and delay gastric emptying, with a minimal effect on HbA1c in individuals with mild T2D. Further research is needed to confirm its applicability in advanced disease stages and to establish long-term metabolic benefits.