BACKGROUND Identifying patients at high risk of diabetic kidney disease (DKD) helps improve clinical outcome. PURPOSE To establish a model for predicting DKD. DATA SOURCES The derivation cohort was from a meta-analysis. The validation cohort was from a Chinese cohort. STUDY SELECTION Cohort studies that reported risk factors of DKD with their corresponding risk ratios (RRs) in patients with type 2 diabetes were selected. All patients had estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m² and urinary albumin-to-creatinine ratio (UACR) <30 mg/g at baseline. DATA EXTRACTION Risk factors and their corresponding RRs were extracted. Only risk factors with statistical significance were included in our DKD risk prediction model. DATA SYNTHESIS Twenty cohorts including 41,271 patients with type 2 diabetes were included in our meta-analysis. Age, BMI, smoking, diabetic retinopathy, hemoglobin A_1c, systolic blood pressure, HDL cholesterol, triglycerides, UACR, and eGFR were statistically significant. All these risk factors were included in the model except eGFR because of the significant heterogeneity among studies. All risk factors were scored according to their weightings, and the highest score was 37.0. The model was validated in an external cohort with a median follow-up of 2.9 years. A cutoff value of 16 was selected with a sensitivity of 0.847 and a specificity of 0.677. LIMITATIONS There was huge heterogeneity among studies involving eGFR. More evidence is needed to power it as a risk factor of DKD. CONCLUSIONS The DKD risk prediction model consisting of nine risk factors established in this study is a simple tool for detecting patients at high risk of DKD.

Background: Berberine is a plant alkaloid that has multiple beneficial effects against intestine inflammation. In our previous study, we have found that berberine also possesses an antidiabetic effect. However, whether berberine is useful in the prevention of type 2 diabetes mellitus (T2DM) through its effect on intestine endocrine function and gut microbiota is unclear. Aim: To investigate the effects of berberine in the prevention of T2DM, as well as its effects on intestine GLP-2 secretion and gut microbiota in ZDF rats. Methods: Twenty Zucker Diabetic Fatty (ZDF) rats were fed a high-energy diet until they exhibited impaired glucose tolerance (IGT). The rats were then divided into two groups to receive berberine (100 mg/kg/d; berberine group) or vehicle (IGT group) by gavage for 3 weeks. Five Zucker Lean (ZL) rats were used as controls. Fasting blood glucose (FBG) was measured, an oral glucose tolerance test was performed, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. Intestinal expression of TLR-4, NF-κB, TNF-α, mucin, zona occludens-1 (ZO-1) and occludin were assessed (immunohistochemistry). Plasma levels and glutamine-induced intestinal secretion of glucagon-like peptide-1 (GLP-1) and GLP-2 were measured (enzyme-linked immunosorbent assay). The plasma lipopolysaccharide (LPS) level was measured. Fecal DNA extraction, pyrosequencing, and bioinformatics analysis were performed. Results: After 3 weeks of intervention, diabetes developed in all rats in the IGT group, but only 30% of rats in the berberine group. Treatment with berberine was associated with reductions in food intake, FBG level, insulin resistance, and plasma LPS level, as well as increases in fasting plasma GLP-2 level and glutamine-induced intestinal GLP-2 secretion. Berberine could increase the goblet cell number and villi length, and also reverse the suppressed expressions of mucin, occludin, ZO-1 and the upregulated expressions of TLR-4, NF-κB and TNF-α induced in IGT rats (P<0.05). Berberine also improved the structure of the gut microbiota and restored species diversity. Conclusion: Berberine may slow the progression of prediabetes to T2DM in ZDF rats by improving GLP-2 secretion, intestinal permeability, and the structure of the gut microbiota.

Background: Treatment with the alpha-glucosidase inhibitor (AGI) acarbose is associated with a significant reduction the risk of cardiovascular events. However, the underlying mechanisms of this effect are unclear. AGIs were recently suggested to participate in stimulating glucagon-like peptide 1 (GLP-1) secretion. We therefore examined the effects of a 24-week treatment of acarbose on endogenous GLP-1, nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and carotid intima-media thickness (CIMT) in newly diagnosed patients with type 2 diabetes (T2D). Methods: Blood was drawn from 24 subjects (14 male, 10 female, age: 50.7 ± 7.36 years, BMI: 26.64 ± 3.38 kg/m², GHbA1c: 7.00 ± 0.74%) with drug-naïve T2D at 0 and 120 min following a standard mixed meal for the measurements of active GLP-1, NO and NOS. The CIMT was measured prior to and following 24 weeks of acarbose monotherapy (mean dose: 268 mg daily). Results: Following 24 weeks of acarbose treatment, both fasting and postprandial plasma GLP-1 levels were increased. In patients with increased postprandial GLP-1 levels, serum NO levels and NOS activities were also significantly increased and were positively related to GLP-1 levels. Although the CIMT was not significantly altered following treatment with acarbose, a decreased CIMT was negatively correlated with increased GLP-1 levels. Conclusions: Twenty-four weeks of acarbose monotherapy in newly diagnosed patients with T2D is associated with significantly increased levels of both fasting and postprandial GLP-1 as well as significantly increased NO levels and NOS activity for those patients in whom postprandial GLP-1 levels were increased. Therefore, the benefits of acarbose on cardiovascular risk may be related to its stimulation of GLP-1 secretion.