Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], −1.04[−1.19, −0.89]%) and BBR-alone group (−0.99[−1.16, −0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (−0.59[−0.75, −0.44]%, −0.53[−0.68, −0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).

The Triglyceride-Glucose Index (TyG) has been proposed as a predictor to mortality, yet its association remains incompletely understood for individuals with or without chronic kidney disease (CKD). We analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999-2018. CKD was defined as eGFR level <60 ml/min/1.73 m² or urinary albumin creatinine ratio ≥30 mg/g. We employed the Cox proportional-hazards model to evaluate the incident risk of mortality associated with TyG among both non-CKD and CKD individuals. In the current analysis, 19,426 individuals were without CKD, while 2975 individuals had CKD. The overall mean TyG was 8.65, with significant difference between non-CKD and CKD individuals (8.60 vs 8.95, P < 0.001). The TyG index exhibited linear associations with incident cardiovascular disease (CVD) mortality and all-cause mortality among non-CKD and CKD individuals, respectively. A per-unit increase in the TyG index was significantly associated with CVD mortality for both non-CKD (HR = 1.24, 95%CI = 1.09-1.41) and CKD participants (HR = 1.19, 95%CI = 1.04-1.36), with no significant difference in the associations between the two groups (P = 0.091). For both non-CKD and CKD participants, TyG index was significantly associated with CVD mortality and all-cause mortality among those with age <65, but not for those with age ≥65. Our findings underscore the TyG index's as a valuable predictive tool for assessing the risk of all-cause and CVD mortality in both individuals with and without CKD.

Background: To investigate the different efficacies of glycemic control between basal and premixed insulin in participants with type 2 diabetes (T2DM) when non‐insulin medications fail to reach treatment targets.Methods: This was a prospective, large‐scale, real‐world study at 10 diabetes centers in China. Between June 2017 and June 2021, we enrolled 1104 T2DM participants initiated with either once‐daily basal insulin or twice‐daily premixed insulin when the glycosylated hemoglobin (HbA1c) control target was not met after at least two non‐insulin agents were administered. A Cox proportional hazards regression model adjusting for multiple influencing factors was performed to compare the different effects of basal and premixed insulin on reaching the HbA1c control target.Results: At baseline, basal insulin (57.3%) was prescribed more frequently than premixed insulin (42.7%). Patients with a higher body mass index (BMI) or higher HbA1c levels were more likely to receive premixed insulin than basal insulin (both p < 0.001). After a median follow‐up of 12.0 months, compared to those with premixed insulin, the hazard ratio for reaching the HbA1c target to those with basal insulin was 1.10 (95% CI, 0.92‐1.31; p = 0.29) after adjustment, and less weight gain was observed in those with basal insulin than with premixed insulin (percentage change of BMI from baseline −0.37[5.50]% vs 3.40[6.73]%, p < 0.0001).Conclusions: In this real‐world study, once‐daily basal insulin was more frequently prescribed and had similar glycemic control effects but less weight gain compared with twice‐daily premixed insulin when used as initiation therapy for those in whom glycemic control with non‐insulin medications failed.

Background Chronic kidney disease (CKD) is a complex condition with diverse etiology and outcomes. Utilizing a data-driven clustering approach holds promise in identifying distinct CKD subgroups associated with specific risk profiles for death. Methods Unsupervised consensus clustering was utilized to classify chronic kidney disease (CKD) into subtypes based on 45 baseline characteristics in a cohort of 6,526 participants from the US National Health and Nutrition Examination Survey (NHANES) spanning the years 1999–2000 to 2017–2018.We examined the associations between CKD subgroups and clinical endpoints related to mortality, including all-cause mortality, cardiovascular disease mortality, cancer mortality, and mortality due to other causes. Results A total of 6,526 individuals with CKD were classified into four clusters at baseline. Cluster 1 (n = 508) comprised patients with relatively favorable levels of cardiac and kidney function markers, lower prevalence of cancer and higher prevalence of obesity, lower medication usage, and younger age. Cluster 4 (n = 2,029) comprised patients with the worst cardiac and kidney function markers. The characteristics of cluster 2 (n = 1,439) and 3 (n = 2,550) fell in between these two clusters. From cluster 1 to cluster 4, we observed a gradual increase in the hazard ratios of all-cause mortality, cardiovascular disease mortality, and mortality due to other causes. Additionally, further sensitivity analysis revealed patient heterogeneity among predefined subgroups with similar baseline kidney function and mortality risks. Conclusions Consensus clustering integrated baseline clinical and laboratory measures, revealing distinct CKD subgroups with markedly different risks of death, suggesting that further examination of patient subgroups could advance precision medicine.