Development and assessment of diabetic nephropathy prediction model using hub genes identified by weighted correlation network analysis.

Diabetic nephropathy (DN) is one microvascular complication of diabetes. About 30% of diabetic patients can develop DN, which is closely related to the high incidence and mortality of heart diseases, and then develop end-stage renal diseases. Therefore, early detection and screening of high-risk patients with DN is important. Herein, we explored the differences of serum transcriptomics between DN and non-DN in type II diabetes mellitus (T2DM) patients. We obtained 110 target genes using weighted correlation network analysis. Gene Ontology enrichment analysis indicates these target genes are mainly related to membrane adhesion, alpha-amino acid biosynthesis, metabolism, and binding, terminus, inhibitory synapse, clathrinid-sculpted vesicle, kinase activity, hormone binding, receptor activity, and transporter activity. Kyoto Encyclopedia of Genes and Genomes analysis indicates the process of DN in diabetic patients can involve synaptic vesicle cycle, cysteine and methionine metabolism, N-Glycan biosynthesis, osteoclast differentiation, and cAMP signaling pathway. Next, we detected the expression levels of hub genes in a retrospective cohort. Then, we developed a risk score tool included in the prediction model for early DN in T2DM patients. The prediction model was well applied into clinical practice, as confirmed by internal validation and several other methods. A novel DN risk model with relatively high prediction accuracy was established based on clinical characteristics and hub genes of serum detection. The estimated risk score can help clinicians develop individualized intervention programs for DN in T2DM. External validation data are required before individualized intervention measures.

Maternal and paternal histories differentially influence risks for diabetes, insulin secretion and insulin resistance in a Chinese population.

AIMS/INTRODUCTION: To investigate the differential effects of maternal versus paternal history of diabetes on the risks for diabetes and prediabetes, as well as on insulin secretion and resistance in Chinese individuals. MATERIALS AND METHODS: From the 2007 to 2008 China National Diabetes and Metabolism Disorders Study, 39,244 participants were included and divided into four categories: negative parental history, paternal history only (PH), maternal history only (MH), and both paternal and maternal history. RESULTS: The age- and sex-standardized prevalence rates of diabetes in the negative parental history, PH, MH, and both paternal and maternal history groups were 8.59, 12.56, 15.86 and 29.81%, respectively. The prevalence rates of impaired glucose metabolism were 24.13, 25.41, 31.13 and 50.80%, with the prevalence in the MH group being significantly higher than that in the PH group. Compared with that in the FH0 group, the risks of diabetes in the PH, MH, and both paternal and maternal history groups were 2.01-, 2.67- and 6.37-fold greater, and the risks of impaired glucose metabolism were 1.28-, 1.65- and 3.45-fold greater. In addition, MH had a significantly greater impact on impaired glucose metabolism than PH (PMHvsPH  = 0.0292). Regression analyses suggested MH was associated with homeostatic model assessment for ß-cell function (ß[SE] = -0.0910[0.0334], P = 0.0065), insulinogenic index (-0.1866[0.0550], P = 0.0007), homeostatic model assessment for insulin resistance (0.0662[0.0227], P = 0.0036) and Matsuda Index [-0.0716(0.0203), P = 0.0004]. PH was specifically associated with homeostatic model assessment for insulin resistance (0.1343[0.0267], P < 0.0001) and Matsuda Index (-0.1566[0.0243], P < 0.0001), but the effects were stronger than those of MH (PMHvsPH  = 0.0431, 0.0054). CONCLUSIONS: MH and PH differentially influence the risks for diabetes, insulin secretion, and insulin resistance in the Chinese population, suggesting they participate in the pathogenesis of diabetes through different mechanisms.

The chronic hepatotoxicity assessment of the herbal formula Zishen Yutai pill.

Zishen Yutai pill (ZYP) is an oriental herbal formula, while hepatotoxicity assessment of ZYP was rarely evaluated. Therefore, our aim is to re-evaluate its hepatotoxicity in both normal and carbon tetrachloride (CCl4) induced chronic liver injury rats. In the normal model, two doses of ZYP (1.575 and 9.450 g kg-1 d-1; i.e. 1 × , 6 × clinical doses) were given orally to rats for 24 weeks. In the chronic liver injury model, 10% CCl4 was administered to rats abdominally twice a week at a dose of 5 mL kg-1 for 12 consecutive weeks. Administration time started from 4 weeks after the beginning of CCl4 treatment. Toxicological parameters included mortality, body weight, food consumption, clinical signs, biochemical parameters, gross observation, organ weight, necropsy findings and histopathology were monitored. In the normal model, we found no any mortality or abnormality in clinical signs, relative liver weight, biochemical parameters and histopathology in ZYP treatment groups. In the chronic liver injury model, liver damage related parameter such as ALT was elevated at the high dose of ZYP treatment in contrast to the CCl4-treated group (P < 0.01). In histopathological assessment, there were no significant difference between ZYP treatment groups and CCl4-treated group. No observed adverse effect on livers were established for 9.450 g kg-1 d-1 ZYP in the normal rats and 9.450 g kg-1 d-1 ZYP in the injury rats.

Prevalence and associated factors of microalbuminuria in Chinese individuals without diabetes: cross-sectional study.

OBJECTIVE: To investigate the prevalence of microalbuminuria (MAU) among Chinese individuals without diabetes and the relationship between MAU and metabolic factors, individual socioeconomic status (SES), and regional economic development level. DESIGN: Cross-sectional study of prevalence of MAU. SETTING: 152 urban street districts and 112 rural villages from northeast, north, east, south central, northwest and southwest China. PARTICIPANTS: 46 239 participants were recruited using a multistage stratified sampling design from 2007 to 2008. A total of 41 290 participants without diabetes determined by oral glucose tolerance test were included in the present study. Urine albumin/creatinine ratio results of 35 430 individuals were available. PRIMARY AND SECONDARY OUTCOME MEASURES: Positive detection of MAU was determined using an ACR of 22.1-299.9 mg/g in men 30.9-299.9 mg/g in women. RESULTS: The prevalence of MAU in men was 22.4% and 24.5% in women. In developed, intermediate-developed and under-developed areas, the prevalence of MAU in men was 20.7%, 21.9% and 32.5%, respectively; in women the prevalence was 19.6%, 26.0% and 29.5%, respectively. The prevalence of MAU increased as the number of metabolic disorders present increased, and as the number of lower SES components increased (farmer, below university education level and low income). Prevalence of MAU in developed and intermediate developed areas had adjusted risk ratios of 0.52 (95% CI 0.42 to 0.60) and 0.65 (95% CI 0.57 to 0.76), respectively. Multivariate logistic analyses demonstrated MAU was strongly associated with older age, high-blood pressure, higher blood glucose low education level, low occupational level and residence in under-developed region. CONCLUSIONS: Several factors had independent correlations to MAU in China: older age, metabolic abnormalities, lower SES level and living in economically under-developed areas, which encourage the development of strategies to lower the risk for MAU in these susceptible populations.