MiR-130b increases fibrosis of HMC cells by regulating the TGF-ß1 pathway in diabetic nephropathy.

Basement membrane thickening, glomerular hypertrophy, and deposition of multiple extracellular matrix characterize the pathological basis of diabetic nephropathy (DN), a condition which ultimately leads to glomerular and renal interstitial fibrosis. Here, we identified a novel microRNA, miR-130b, and investigated its role and therapeutic efficacy in alleviating DN. Introduction of miR-130b dramatically increased cell growth and fibrosis in DN cells. We found that transforming growth factor (TGF)-ß1 was a functional target of miR-130b in human glomerular mesangial cells (HMCs) and overexpression of miR-130b increased expressions of the downstream signaling molecules of TGF-ß1, t-Smad2/3, p-Smad2/3, and SMAD4. An ectopic application of miR-130b increased messenger RNA and protein expressions of collagen type I (colI), colIV, and fibronectin, whose expression levels were correlated with the expression of miR-130b. Taken together, the findings of this study reveal that miR-130b in HMC cells plays an important role in fibrosis regulation and may thus be involved with the pathogenesis of DN. Therefore, miR-130b may serve as a novel therapeutic target for the prevention and the treatment of DN.

Hypothalamic-Pituitary-Gonadal Axis in Aging Men and Women: Increasing Total Testosterone in Aging Men.

BACKGROUND: Aging is associated with variations in hypothalamic-pituitary-gonadal (HPG) axis hormones. However, it is not clear how aging changes these hormones. This study examined the natural alterations in the HPG axis in aging men and women in China. METHODS: Data were obtained from our cross-sectional study (SPECT-China) in 16 areas of three provinces in East China between February and June 2014. There were 6,825 subjects selected, including 2,908 men and 3,917 women aged 25-93 years who had no diseases affecting HPG hormones and did not take exogenous supplements. Total testosterone (TT), estradiol (E2), free testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured. RESULTS: In men, the ranges of the 10-90th percentiles for each hormone were as follows: TT, 9.9-23.4 nmol/l; SHBG, 20.6-79.54 nmol/l; E2, 34.84-187 pmol/l. TT values were higher in men aged 25-30 years than in those aged 31-35 years and began to increase progressively at the age of 41-50 years until men reached their eighties. The unadjusted annual age trend (ß) was 0.079 nmol/l/year (p < 0.001). A linear regression analysis, after full adjustment for demographic variables, metabolic factors, other hormones, lifestyle and co-morbidities, showed that higher TT levels were still associated with aging (p < 0.05). However, the ratio of TT to LH decreased with age (ß = -0.272/year, p < 0.001). E2 and SHBG increased with age (ß = 1.774 pmol/l/year and 1.118 nmol/l/year, respectively, p < 0.001). In women, the 10-90th percentile range of E2 was 32.79-565.8 pmol/l. E2 began to decrease at the age of 46-50 years, declined sharply at the age of 51-55 years (ß = -5.73 pmol/l/year, p < 0.001) and then stabilized at a low concentration after the age of 55 years. The 10-90th percentile ranges of LH and FSH in men were 2.4-9.2 and 3.4-15.5 IU/l, and in women they were 3-36.6 and 4-89.28 IU/l, respectively. FSH increased by 7.11% per annum in men and by 12.76% per annum in women, but LH increased by only approximately 4.00% per annum in both sexes. CONCLUSIONS: The influence of aging on the HPG axis is sex dependent. The pattern of age-related TT was different in Chinese Han men when compared with previous studies in Western populations. TT values increased in aging men, so it is not suitable to estimate the life quality of older Chinese men just based on TT.

Investigation of vitamin D status and its correlation with insulin resistance in a Chinese population.

OBJECTIVE: Although many studies worldwide have focused on the relationship between vitamin D and insulin resistance, results remain controversial. Furthermore, concentrations of serum 25-hydroxyvitamin D (25(OH)D) in the Chinese population are unclear. We aimed to investigate vitamin D status and its correlation with insulin resistance among a Chinese adult population. DESIGN: Serum 25(OH)D, fasting blood glucose, fasting insulin, glycated Hb (HbA1c) and other metabolic parameters were assessed. Neck circumference, waist circumference, hip circumference, weight and height were also measured. Lifestyle factors including smoking and drinking status were obtained. Diabetes mellitus was diagnosed by HbA1c according to the 2010 American Diabetes Association criteria. SETTING: Eastern China. SUBJECTS: Of 7200 residents included, 6597 individuals were ultimately analysed. RESULTS: We enrolled 2813 males (mean age 52·7 (sd 13·5) years) and 3784 females (52·3 (sd 13·5) years); mean serum 25(OH)D concentration was 43·1 (sd 11·6) and 39·6 (sd 9·8) nmol/l, respectively. Additionally, 83·3 % of participants were 25(OH)D deficient. A significant difference in 25(OH)D was observed between males and females in winter and spring (P<0·001). Furthermore, 25(OH)D concentrations were inversely associated with the homeostasis model assessment of insulin resistance (HOMA-IR) in the overweight and pre-diabetic populations. After adjusting for several variables, 25(OH)D was significantly associated with HOMA-IR in winter. When 25(OH)D values were categorized into quartiles, HOMA-IR was significantly associated with decreasing 25(OH)D. CONCLUSIONS: The majority of the Chinese population was vitamin D deficient and this deficiency was negatively associated with insulin resistance, particularly in the overweight and pre-diabetic populations. Moreover, these associations might be more evident in the winter.

Low vitamin D levels and non-alcoholic fatty liver disease, evidence for their independent association in men in East China: a cross-sectional study (Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China)).

Recent studies have suggested an association between vitamin D and non-alcoholic fatty liver disease (NAFLD); however, some results are subject to debate. This study was carried out to evaluate the correlation between NAFLD and vitamin D in men and women in East China. The data were obtained from a cross-sectional study that focused on the health and metabolic status of adults in sixteen areas of East China. According to ultrasonic assessments, the patients were divided into normal and NAFLD groups. Demographic characteristics and biochemical measurements were obtained. Binary logistic regression analysis was used to explore the association. In total, 5066 subjects were enrolled, and 2193 (43·3 %) were diagnosed with NAFLD; 84·56 % of the subjects showed vitamin D deficiency. Subjects with high vitamin D levels had a lower prevalence of NAFLD, particularly male subjects. Within the highest quartile of vitamin D levels, the prevalence of NAFLD was 40·8 %, whereas the lowest quartile of vitamin D levels showed a prevalence of 62·2 %, which was unchanged in women across the vitamin D levels. Binary logistic analysis showed that decreased vitamin D levels were associated with an increased risk of NAFLD (OR 1·54; 95 % CI 1·26, 1·88). This study suggests that vitamin D levels are significantly associated with NAFLD and that vitamin D acts as an independent factor for NAFLD prevalence, particularly in males in East China. Vitamin D interventional treatment might be a new target for controlling NAFLD; elucidating the mechanism requires further research.

A multi-facet comparative analysis of neuromyelitis optica spectrum disorders in patients with seropositive and seronegative AQP4-IgG.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD), a rare, serious, demyelinating disease of the central nervous system (CNS), is associated with immunoglobulin G (IgG) antibodies targeting aquaporin-4 (AQP4-IgG). This study retrospectively analyzed the clinical features of 67 patients. 49 and 18 of 67 cases (male/female: 11/56) were AQP4-IgG (+) and AQP4-IgG (-), respectively. The initial symptoms were optic neuritis [n = 34, AQP4-IgG (+)/(-): 31/3], myelitis [n = 18, AQP4-IgG(+)/(-): 13/5], co-occurrence of ON and myelitis [n = 15, AQP4-IgG (+)/(-): 5/10]. CONCLUSIONS: There was no statistically significant difference between the 2 groups in terms of ages, and magnetic resonance imaging findings, but the patients had a significant difference (P <.05) in sex, the course of disease and Expanded Disability Status Scale (EDSS) scores after drug treatment. Patients with AQP4-IgG (-) are likely to have a better prognosis and a favorable monophasic course.

Combined Association of Vitamin D and Sex Hormone Binding Globulin With Nonalcoholic Fatty Liver Disease in Men and Postmenopausal Women: A Cross-Sectional Study.

This study aimed to explore the combined associations of 25(OH)-vitamin D and sex hormone binding globulin (SHBG) with nonalcoholic fatty liver disease (NAFLD) in men and postmenopausal women. Our data, which were based on the population, were collected from 16 sites in East China in 2014. There were 2700 men with a mean age of 53 years and 1461 women over 55 who were considered postmenopausal enrolled in the study. Levels of 25(OH)D and SHBG were measured using chemiluminescence assay. NAFLD was measured using liver ultrasound. Multivariable-adjusted logistic regression models examined associations of 25(OH)D and SHBG tertiles with odds of mild and moderate-severe NAFLD. Both the low 25(OH)D and low SHBG groups were significantly associated with higher odds of mild NAFLD (men: OR 1.37, 95% CI 1.05, 1.78 in low 25(OH)D group; OR 1.73, 95% CI 1.23, 2.45 in low SHBG group; women: OR 1.51, 95% CI 1.08, 2.12 in low 25(OH)D group; OR 2.16, 95% CI 1.48, 3.14 in low SHBG group) and moderate-severe NAFLD (men: OR 1.61, 95% CI 1.24, 2.10 in low 25(OH)D group; OR 3.42, 95% CI 2.41, 4.87 in low SHBG group; women: OR 1.66, 95% CI 1.14, 2.42 in low 25(OH)D group; OR 6.84, 95% CI 4.31, 10.84 in low SHBG group). However, the combined association of low 25(OH)D and low SHBG was much larger, especially in moderate-severe NAFLD (men: OR 6.57, 95% CI 3.87, 11.18; women: OR 8.16, 95% CI 3.98, 16.73). The associations were independent of age, total testosterone, abdominal obesity, diabetes, and lipid profile. The negative associations of 25(OH)D and SHBG levels with NAFLD are strongest when viewed in combination in men and postmenopausal women. Further studies should determine the cause-effect relationship and investigate the underlying mechanisms of this finding.

Modulation of Microbiota-Gut-Brain Axis by Berberine Resulting in Improved Metabolic Status in High-Fat Diet-Fed Rats.

OBJECTIVE: To investigate whether or not berberine could improve metabolic status of high-fat-fed rats through modulation of microbiota-gut-brain axis. METHODS: Berberine was administered on high-fat-fed Sprague-Dawley rats. Brain-gut hormones were detected, and changes of gut microbiota were analyzed by 16S rRNA gene sequencing. RESULTS: Berberine could reduce weight gain and lipolysis in the high-fat diet-fed group. Moreover, trends of ameliorated insulin resistance and decreased endogenous glucose production were observed. In addition, the microbiota-gut-brain axis was found to be modulated, including structural and diversity changes of microbiota, elevated serum glucagon-like peptide-1 and neuropeptide Y level, decreased orexin A level, up-regulated glucagon-like peptide-1 receptor mRNA level as well as ultra-structural improvement of the hypothalamus. CONCLUSION: Taken together, our findings suggest that berberine improved metabolic disorders induced by high-fat diet through modulation of the microbiota-gut-brain axis.

Follicle-stimulating hormone associates with prediabetes and diabetes in postmenopausal women.

AIMS: No study explores the association between follicle-stimulating hormone (FSH) and glucose metabolism in general women. We aim to investigate whether the variation of FSH is associated with prediabetes and diabetes in postmenopausal women. METHODS: Our data were from survey on prevalence in East China for metabolic diseases and risk factors in 2014. Thousand six hundred and ten postmenopausal women at the age of 55-89 who were not using hormone replacement therapy were selected. Prediabetes and diabetes were defined according to American Diabetes Association 2014 criteria. FSH, luteinizing hormone, total testosterone and estradiol were measured by chemiluminescence. Multinomial logistic analyses were used for the association of FSH with prediabetes and diabetes, and linear regression for the association of FSH with fasting plasma glucose (FPG) and HbA1c. RESULTS: Among the participants, 778 (48.3 %) had prediabetes and 121 (7.5 %) had newly diagnosed diabetes. In linear regression, after full adjustment for demographic variables, metabolic factors, E2 and LH, FSH was associated with FPG and HbA1c (P < 0.05). In logistic regression, increased quartiles of FSH were associated with significantly decreased odds ratios of prediabetes and diabetes (P for trend <0.01). This association was attenuated by waist circumference and HOMA-IR, but persisted in fully adjusted model (P for trend <0.05) in which, for the lowest compared with the highest quartile of FSH, the odds ratios of prediabetes and diabetes were 1.93 (95 % CI 1.21-3.08; P < 0.01) and 3.02 (95 % CI 1.10-8.31; P < 0.05), respectively. CONCLUSIONS: Low FSH was associated with prediabetes and diabetes in postmenopausal women. The associations might be partially explained by adiposity and insulin resistance.

Neck circumference as an independent indicator to non-alcoholic fatty liver disease in non-obese men.

BACKGROUND: To investigate the relationship of the neck circumference (NC) with non-alcoholic fatty liver disease (NAFLD) in non-obese Chinese population. METHODS: Our data were obtained from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China in 2014. Subjects with a BMI ≥ 18.5 kg/m(2) and < 25 kg/m(2) were considered normal weight. A total of 2668 participants aged 18-89 were identified for analysis. Anthropometric indices, biochemical parameters, clinical characteristics and abdominal ultrasound were measured. Independent predictors of NAFLD were identified by multiple logistic regressions. RESULTS: The overall prevalence of NAFLD was 10.94 % in this study population and men had a higher prevalence than women (19.89 % vs 7.48 %, P < 0.01). The mean NC was greater in NAFLD subjects compared with other groups in both genders (P < 0.01). NC was correlated to BMI, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, insulin, HOMA-IR, triglycerides and ALT, regardless of sex. In the highest quartile of NC levels in men but not in women, the risks were substantially higher for NAFLD [odds ratio 2.18, (95 % confidence interval 1.16-4.13)] (P < 0.001 for trend) after adjusting for potential confounding factors. CONCLUSION: NC was an independent indicator for NAFLD in normal weighted men.

Is Exposure to Famine in Childhood and Economic Development in Adulthood Associated With Diabetes?

CONTEXT: The Chinese were afflicted by great famine between 1959 and 1962. These people then experienced rapid economic development during which the gross domestic product per capita increased from $28 in 1978 to $6807 in 2013. We hypothesize that these two events are associated with the booming rate of diabetes in China. OBJECTIVE: We aimed to explore whether exposure to famine in early life and high economic status in adulthood was associated with diabetes in later life. DESIGN AND SETTING: Our data of 6897 adults were from a cross-sectional Survey on Prevalence in East China for Metabolic Diseases and Risk Factors study in 2014. Among them, 3844 adults experienced famine during different life stages and then lived in areas with different economic statuses in adulthood. MAIN OUTCOME MEASURE: Diabetes was considered as fasting plasma glucose of 7.0 mmol/L or greater, hemoglobin A1c of 6.5% or greater, and/or a previous diagnosis by health care professionals. RESULTS: Compared with nonexposed subjects, famine exposure during the fetal period (odds ratio [OR]1.53, 95% confidence interval [CI]1.09-2.14) and childhood (OR 1.82, 95% CI 1.21-2.73) was associated with diabetes after adjusting for age and gender. Further adjustments for adiposity, height, the lipid profile, and blood pressure did not significantly attenuate this association. Subjects living in areas with high economic status had a greater diabetes risk in adulthood (OR 1.46, 95% CI 1.20-1.78). In gender-specific analyses, fetal-exposed men (OR 1.64, 95% CI, 1.04-2.59) and childhood-exposed women (OR 2.81, 95% CI, 1.59-4.97) had significantly greater risk of diabetes. CONCLUSIONS: The rapid increase in the prevalence of diabetes in middle-aged and elderly people in China is associated with the combination of exposure to famine during the fetal stage and childhood and high economic status in adulthood. Our findings may partly explain the booming diabetes phenomenon in China.