OBJECTIVE:To assess the association between glycated haemoglobin (HbA1c) variability and risk of renal function decline in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS:A comprehensive search was carried out in PubMed, Embase, Web of Science and the Cochrane Library (until 12 March 2024). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines were followed for this meta-analysis. HbA1c variability was presented as indices of the standard deviation (SD), coefficient of variation (CV), HbA1c variability score (HVS) and haemoglobin glycation index (HGI). This meta-analysis was performed using random-effect models. RESULTS:Eighteen studies met the objectives of this meta-analysis. The analyses showed positive associations between HbA1c variability and kidney function decline, with hazard ratio (HR) 1.26 (95% confidence interval [CI] 1.15-1.38) for high versus low SD groups, HR 1.47 (95% CI 1.30-1.65) for CV groups, HR 1.32 (95% CI 1.10-1.57) for HVS groups and HR 1.53 (95% CI 1.05-2.23) for HGI groups. In addition, each 1% increase in SD and CV was linked to kidney function decline, with HR 1.26 (95% CI 1.17-1.35), and 1.13 (95% CI 1.03-1.23), respectively. Also, each 1-SD increase in SD of HbA1c was associated with deterioration in renal function, with HR 1.17 (95% CI 1.07-1.29). CONCLUSIONS:The four HbA1c variability indicators were all positively associated with renal function decline progression; therefore, HbA1c variability might play an important and promising role in guiding glycaemic control targets and predicting kidney function decline progression in T2DM.

We aimed to explore the medium- and long-term (≥12 weeks) effects of dapagliflozin on serum uric acid (SUA) level in patients with type 2 diabetes mellitus (T2DM) in the real world study and to explore the influencing factors of dapagliflozin on reducing SUA level. This observational, prospective cohort study was based on the real world. There were 77 patients included in this study. They were divided into two groups. Patients in treatment group (n = 38) were treated as dapagliflozin 10 mg/d combined with therapy of routine glucose-lowering drugs (GLDs), and patients in the control group (n = 39) were treated with their routine GLDs. All measurements of physical examinations, blood, and urine samples, including age, sex, weight, height, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and SUA, were collected at baseline for all patients in these two groups and repeated after 12, 24, and 48 weeks of therapy. We compared the changes of metabolic indicators including SUA in these two groups to evaluate the effects of dapagliflozin and analyzed its influencing factors. In the dapagliflozin group, mean SUA levels significantly decreased from 334.2 ± 99.1 μmol/L at baseline to 301.9 ± 73.2 μmol/L after 12 weeks therapy (t = 2.378, p = 0.023). There was no significant statistical difference of SUA levels after 24 weeks treatment of dapagliflozin compared with 12-week and 48-week treatment with dapagliflozin (p > 0.05). We found that baseline SUA had a significant impact on the effect of dapagliflozin on reducing SUA (OR 1.014, 95%CI 1.003–1.025, p = 0.014) by logistic regression analysis. Receiver operating characteristic (ROC) curve showed that T2DM patients with SUA level ≥ 314.5 μmol/L had relative accuracy in recognizing the good effects of dapagliflozin on reducing SUA (sensitivity 76.9%, specificity 76.2%). Combination therapy of dapagliflozin with routine blood-glucose-lowering drugs in T2DM patients showed the significant and sustained stable effect of lowering SUA level in this real-world study.

Abstract Aim To investigate the influence of sodium/glucose cotransporter‐2 inhibitors (SGLT‐2i) on renal function during the course of its administration, particularly in the initial weeks. Materials and Methods Randomized controlled trials (RCTs) related to SGLT‐2i were searched in databases (MEDLINE, EMBASE, and Cochrane Central Register) from the database's inception to August 31, 2021. All RCTs reported the kidney outcomes of SGLT2i versus active or placebo control were included, regardless of the presence of diabetes in the patients and the baseline estimated glomerular filtration rate (eGFR). The Cochrane Collaboration risk of bias tool was used to assess the quality of the included studies. All outcome comparisons were performed using the RevMan 5.4 software. Results Eleven RCTs with 58 534 participants reporting prespecified renal outcomes were identified. There was no heterogeneity in the baseline eGFR and urine albumin‐to‐creatinine ratio in the included studies. In the initial 2–4 weeks, there was an acute decline of eGFR in the SGLT‐2i group compared with placebo group (weighted mean difference [WMD] −3.35 ml/min/1.73 m2; 95% CI, −3.81 to −2.90; I2 = 35%, p = .15); When compared to baseline eGFR in the SGLT‐2i group, the WMD was −4.02 ml/min/1.73 m2 (95% confidence interval [CI], −3.61 to −4.44; I2 = 0%, p = .45). The renoprotective effect gradually appeared, and the decline rate of eGFR in the SGLT‐2i group was sustained slower than placebo. However, the statistically significant benefit of SGLT‐2i did not appear until the 104th week (the second year) (WMD 0.35 ml/min/1.73 m2, 95% CI, 0.04 to 0.66; I2 = 45%, p = .08). Subgroup analysis showed SGLT‐2i had a similar benefit on renal function regardless of baseline eGFR values. Conclusion SGLT‐2i consistently slowed the deterioration of eGFR since the early stage of administration, even in patients with chronic kidney disease. However, there was an acute decline in eGFR in the initial 2–4 weeks; afterwards the renoprotective effect of SGLT‐2i gradually appeared and remained stable in the next few years.

Objective:The decline in nutritional status in patients with severe pneumonia may contribute to an increase in in-hospital mortality. Enteral nutrition support can improve the nutritional status of patients, and is relatively easy to manage, with low cost and fewer serious complications. On the other hand, adverse reactions such as gastric retention and gastric microbiota translocation may increase the incidence of nosocomial pneumonia and increase the uncertainty of patient prognosis. There is no predictive model for in-hospital death in severe pneumonia patients receiving enteral nutrition support. The objective of this study was to investigate the risk factors of in-hospital death in patients with severe pneumonia receiving enteral nutrition support and to establish a prognostic model for such patients.Methods:This was a single-center retrospective study. Patients with severe pneumonia who were hospitalized in Peking Union Medical College Hospital and received enteral nutrition support were included from January 1, 2015 to December 31, 2020. The primary endpoints were in-hospital mortality rate and unordered discharge rate. The independent risk factors were determined using univariate and multifactorial logistic regression analysis, the nomogram scoring model was constructed, and the decision curve analysis (DCA) was performed.Results:A total of 632 severe pneumonia patients who received enteral nutrition support were included. Patients were divided into death and survival groups according to the presence or absence of in-hospital death, and 24 parameters were found with significant differences between groups. Nine parameters were independent predictors of mortality, namely the duration of ventilator use, the presence of malignant hyperplasia diseases, the maximal levels of platelet and prothrombin during hospitalization, and the nadir levels of alanine aminotransferase, serum albumin, sodium, potassium, and blood glucose. Based on these variables, a risk prediction scoring model was established (ROC = 0.782; 95% CI: 0.744 to 0.819, concordance index: 0.772). Calibration curves, DCA, and clinical impact curve were plotted to evaluate the goodness of function, accuracy, and applicability of the predictive nomogram, using the training and test sets. Conclusion:This study summarized the clinical characteristics of patients with severe pneumonia receiving enteral nutrition support and developed a scoring model to identify risk factors and establish prognostic models.

Objective: There is limited data regarding the risk of incident type 2 diabetes mellitus (T2DM) among lean nonalcoholic fatty liver disease (NAFLD) individuals. We performed a meta-analysis of relevant studies.Research design and methods: We collected data using PubMed, Scopus, Cochrane and Web of Science from the databases' inception until December 2022. We included cohort studies in which lean NAFLD was diagnosed through imaging methods or biopsy. Eligible studies were selected according to predefined keywords and clinical outcomes.Results: A total of 16 observational studies with 304,975 adult individuals (7.7% with lean NAFLD) and nearly 1300 cases of incident diabetes followed up over a median period of 5.05 years were included in the final analysis. Patients with lean NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio [HR] 2.72, 95% CI 1.56-4.74; I2 = 93.8%). Compared with the lean without NAFLD group, the adjusted HRs (95% CIs) of incident diabetes for participants in the overweight/obese without NAFLD and overweight/obese with NAFLD groups were 1.32 (0.99- 1.77) and 2.98(1.66-5.32). It appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (random-effects HR 3.48, 95% CI 1.92-6.31). Sensitivity analyses and publication bias did not alter these findings.Conclusions: Lean NAFLD is significantly associated with at least twofold increased risk of incident diabetes in non-overweight subjects. This risk parallels the underlying severity of NAFLD. The presence of NAFLD in non-overweight individuals had a more significant impact on the development of diabetes than being overweight itself.

AimTo investigate the influence of sodium/glucose cotransporter-2 inhibitors (SGLT-2i) on renal function during the course of its administration, particularly in the initial weeks. Materials and MethodsRandomized controlled trials (RCTs) related to SGLT-2i were searched in databases (MEDLINE, EMBASE, and Cochrane Central Register) from the database's inception to August 31, 2021. All RCTs reported the kidney outcomes of SGLT2i versus active or placebo control were included, regardless of the presence of diabetes in the patients and the baseline estimated glomerular filtration rate (eGFR). The Cochrane Collaboration risk of bias tool was used to assess the quality of the included studies. All outcome comparisons were performed using the RevMan 5.4 software. ResultsEleven RCTs with 58 534 participants reporting prespecified renal outcomes were identified. There was no heterogeneity in the baseline eGFR and urine albumin-to-creatinine ratio in the included studies. In the initial 2-4 weeks, there was an acute decline of eGFR in the SGLT-2i group compared with placebo group (weighted mean difference [WMD] -3.35 ml/min/1.73 m(2); 95% CI, -3.81 to -2.90; I-2 = 35%, p = .15); When compared to baseline eGFR in the SGLT-2i group, the WMD was -4.02 ml/min/1.73 m(2) (95% confidence interval [CI], -3.61 to -4.44; I-2 = 0%, p = .45). The renoprotective effect gradually appeared, and the decline rate of eGFR in the SGLT-2i group was sustained slower than placebo. However, the statistically significant benefit of SGLT-2i did not appear until the 104th week (the second year) (WMD 0.35 ml/min/1.73 m(2), 95% CI, 0.04 to 0.66; I-2 = 45%, p = .08). Subgroup analysis showed SGLT-2i had a similar benefit on renal function regardless of baseline eGFR values. ConclusionSGLT-2i consistently slowed the deterioration of eGFR since the early stage of administration, even in patients with chronic kidney disease. However, there was an acute decline in eGFR in the initial 2-4 weeks; afterwards the renoprotective effect of SGLT-2i gradually appeared and remained stable in the next few years.

Background The increase in diabetes worldwide is alarming. Decreased acute insulin response to intravenous glucose tolerance test (IVGTT) during first-phase insulin secretion (FPIS) is a characteristic of diabetes. However, knowledge of the insulin secretion characteristics identified by different time to glucose peak in subjects with different metabolic state is sparse. Aims This study aimed to find different patterns of FPIS in subjects with normal glucose tolerance (NGT) and analyzed the relationship between insulin secretion patterns and the risk for development of type 2 diabetes mellitus (T2DM). Methods A total of 126 subjects were divided into three groups during a 10-min IVGTT, including NGT with time to glucose peak after 3 min (G1, n = 21), NGT with time to glucose peak at 3 min (G2, n = 95), and prediabetes or diabetes with time to glucose peak at 3 min (G3, n = 10). Glucose, insulin, and C-peptide concentrations at 0, 3, 5, 7, and 10 min during the IVGTT were tested. IVGTT-based indices were calculated to evaluate the insulin secretion and insulin sensitivity. Results Age, body mass index (BMI), waist-to-hip ratio, triglyceride (TG), and hemoglobin A1c (HbA1c) of subjects were gradually higher, while high-density lipoprotein cholesterol (HDL-C) was gradually lower from G1 to G3 (p for linear trend <0.05), and the differences between G1 and G2 were also statistically significant (p < 0.05). Glucose peak of most participants in G1 converged at 5 min, and the curves shape of insulin and C-peptide in G2 were the sharpest among three groups. There was no significant difference in all IVGTT-based indices between G1 and G2, but AUCIns, AUCIns/AUCGlu, and △Ins3/△Glu3 in G2 were the highest, and the p-value for linear trend of those indices among three groups were statistically significant (p < 0.05). Conclusions Two patterns of FPIS were in subjects with NGT, while subjects with later time to glucose peak during FPIS might be less likely to develop T2DM in the future.