25-Hydroxyvitamin D Is Associated with Islet Homeostasis in Type-2 Diabetic Patients with Abdominal Obesity.

OBJECTIVE: Islet α cells input is essential for insulin secretion from ß cells. The present study aims to investigate the association between 25-hydroxyvitamin D [25(OH)D] and islet function homeostasis in type-2 diabetes (T2D) patients. METHODS: A total of 4670 T2D patients from seven communities in Shanghai, China were enrolled. The anthropometric indices, biochemical parameters, serum 25(OH)D, and islet function [including C-peptide (C-p) and glucagon] were measured. RESULTS: The fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), glucagon, and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased. Next, the population was divided into two groups: abdominal obesity and non-abdominal obesity groups. After adjustment, the 25(OH)D level was found to be associated with HbA1c, glucagon, and homeostasis model assessment of ß (HOMA-ß) in the non-abdominal obesity group. There was a significant relationship between 25(OH)D and HbA1c, glucagon, HOMA-IR, baseline insulin or C-p in the abdominal obesity group. In the abdominal obesity group, the ordinary least squares (OLS) regression and quantile regression revealed that 25(OH) D was obviously associated with glucagon and fasting C-p levels. In the abdominal obesity group, the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p (P=0.0124). Furthermore, the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation (SD) below the mean (P=0.0002), and lower at the mean of the course of diabetes (P=0.0007). CONCLUSION: 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity. The 25(OH)D influenced C-p in part by influencing glucagon. The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity, in terms of islet homeostasis, is influenced by the course of diabetes.

FSH may mediate the association between HbA1c and bone turnover markers in postmenopausal women with type 2 diabetes.

INTRODUCTION: Recent studies in postmenopausal women have found associations of follicle-stimulating hormone (FSH) levels with both glucose metabolism and bone turnover. The objective of the study was to investigate whether FSH may contribute to suppressed bone turnover markers (BTMs) in postmenopausal women with type 2 diabetes (T2D). MATERIALS AND METHODS: 888 postmenopausal women with T2D, 352 nondiabetes (prediabetes plus normoglycemia) were included from the METAL study. HbA1c, sex hormones, 25-hydroxy vitamin D (25(OH)D), serum procollagen type I N-terminal propeptide (P1NP), and ß-C-terminal telopeptide (ß-CTX) were measured. RESULTS: P1NP and ß-CTX decreased in postmenopausal T2D women compared with nondiabetes controls (both p < 0.001). The major factors responsible for the changes in P1NP were HbA1c (ß = - 0.050, p < 0.001), 25(OH)D (ß = - 0.003, p = 0.006), FSH (ß = 0.001, p = 0.044) and metformin (ß = - 0.109, p < 0.001), for ß-CTX were HbA1c (ß = - 0.049, p < 0.001), body mass index (BMI) (ß = - 0.011, p = 0.005), 25(OH)D (ß = - 0.003, p = 0.003), FSH (ß = 0.002, p = 0.022) and metformin (ß = - 0.091, p = 0.001) in postmenopausal T2D women based on multivariate regression analysis. With the increase in HbA1c, FSH decreased significantly (p for trend < 0.001). Mediation analysis demonstrated that FSH partly mediated the suppression of LnP1NP and Lnß-CTX by HbA1c (ß = - 0.009 and - 0.010, respectively), and Lnß-CTX by BMI (ß = - 0.015) when multiple confounders were considered (all p < 0.05). CONCLUSION: HbA1c was the crucial determinant contributing to the suppression of BTMs. FSH might play a novel mediation role in BTM suppression due to HbA1c or BMI.

National trends in insulin resistance and ß-cell dysfunction among adults with prediabetes: NHANES 2001-2016.

BACKGROUND: Insulin resistance is the central abnormality and mechanism underlying the progression of cardiometabolic-based chronic diseases. This study aimed to evaluate the trends in insulin resistance and ß-cell dysfunction from 2001 to 2016 among US adults with undiagnosed diabetes, prediabetes, and normal glucose regulation and to provide sex-specific information using data from National Health and Nutrition Examination Surveys (NHANES) 2001-2016. METHODS: Data from 14,481 participants aged over 20 years from 8 consecutive 2-year cross-sectional cycles of the NHANES from 2001 to 2016 were used. Updated homoeostasis model assessment 2 (HOMA2: HOMA2%B for ß-cell function and HOMA2IR for insulin resistance) was used as a surrogate measure. We defined the upper sex-specific tertile of HOMA2IR as insulin resistance and the lower corresponding tertile of HOMA2%B as low ß-cell function. RESULTS: In both sexes with undiagnosed diabetes, HOMA2%B (men, P trend = 0.118; women, P trend = 0.184) and HOMA2IR (men, P trend = 0.710; women, P trend = 0.855) remained stable over time. In the prediabetes group, both sexes exhibited significant increasing trends in HOMA2%B (men, P trend < 0.010; women, P trend < 0.010) and HOMA2IR (men, P trend < 0.010; women, P trend < 0.050). Adjusting for waist circumference mildly attenuated the trend in HOMA2IR and insulin resistance in men (P trend < 0.010), but it resulted in no significance in women (P trend = 0.196). In regard to normal glucose regulation, both sexes presented significant decreasing trends in low ß-cell function (men, P trend < 0.050; women < 0.010) and attenuated trends in insulin resistance (men, P trend = 0.196; women, P trend = 0.121). CONCLUSIONS: Over 16 years, insulin resistance demonstrated an increasing trend in adult US population with prediabetes, while ß-cell function showed a compensatory increasing trend. Identifying people with prediabetes early and focusing on reducing insulin resistance as the intervention core, especially controlling central obesity, might increase the opportunity for cardiovascular and diabetes risk reduction.

Cardiovascular and renal burdens of metabolic associated fatty liver disease from serial US national surveys, 1999-2016.

BACKGROUND: Non-communicable chronic diseases have become the leading causes of disease burden worldwide. The trends and burden of "metabolic associated fatty liver disease" (MAFLD) are unknown. We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease (NAFLD). METHODS: Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged ≥20 years from the cross-sectional US National Health and Nutrition Examination Survey periods, 1999 to 2002, 2003 to 2006, 2007 to 2010, and 2011 to 2016. MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity, type 2 diabetes mellitus, or evidence of metabolic dysregulation. RESULTS: The prevalence of MAFLD increased from 28.4% (95% confidence interval 26.3-30.6) in 1999 to 2002 to 35.8% (33.8-37.9) in 2011 to 2016. In 2011 to 2016, among adults with MAFLD, 49.0% (45.8-52.2) had hypertension, 57.8% (55.2-60.4) had dyslipidemia, 26.4% (23.9-28.9) had diabetes mellitus, 88.7% (87.0-80.1) had central obesity, and 18.5% (16.3-20.8) were current smokers. The 10-year cardiovascular risk ranged from 10.5% to 13.1%; 19.7% (17.6-21.9) had chronic kidney diseases (CKDs). Through the four periods, adults with MAFLD showed an increase in obesity; increase in treatment to lower blood pressure (BP), lipids, and hemoglobin A1c; and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus. Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs, myocardial infarction, or stroke. Generally, although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD, the prevalence of MAFLD was significantly higher than that of NAFLD. CONCLUSIONS: From 1999 to 2016, cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD. The absolute cardiorenal burden may be greater for MAFLD than for NAFLD. These data call for early identification and risk stratification of MAFLD and close collaboration between endocrinologists and hepatologists.

Association between blood cadmium and vitamin D levels in the Yangtze Plain of China in the context of rapid urbanization.

BACKGROUND: China has experienced rapid urbanization in the past 30 years. We aimed to report blood cadmium level (BCL) in the rapidly urbanized Yangtze Plain of China, and explore the association between BCL and 25-hydroxyvitamin D (25(OH)D). METHODS: Our data source was the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cross-sectional study (ChiCTR-ECS-14005052, www.chictr.org). We enrolled 3234 subjects from 12 villages in the Yangtze Plain. BCLs were measured by atomic absorption spectrometry. 25(OH)D was measured with a chemiluminescence assay. RESULTS: A total of 2560 (79.2%) subjects were diagnosed with vitamin D deficiency. The median (interquartile range) BCL was 1.80 µg/L (0.60-3.42) for men and 1.40 µg/L (0.52-3.10) for women. In women, mean 25(OH)D concentrations were inversely associated with BCL (0.401, 95% confidence interval: -0.697 to -0.105 nmol/L lower with each doubling of the BCL) after adjustment for age, educational status, current smoking, body mass index, diabetes, and season. However, there was no significant difference in 25(OH)D across the BCL tertiles for men. CONCLUSIONS: BCL in Chinese residents in the Yangtze Plain were much higher than that in developed countries. An inverse association between BCL and 25(OH)D was found in general Chinese women after multivariable adjustment. Future prospective cohort and animal studies are warranted to resolve the direction and temporality of these relationships, and to elucidate the exact mechanisms involved.

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects.

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas. We aimed to investigate the association between euthyroid hormones and islet beta-cell function in general population and non-treated type 2 diabetes mellitus (T2DM) patients. A total of 5089 euthyroid participants (including 4601 general population and 488 non-treated T2DM patients) were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016. Anthropometric indices, biochemical parameters, and thyroid hormones were measured. Compared with general population, non-treated T2DM patients exhibited higher total thyroxine (TT4) and free thyroxine (FT4) levels but lower ratio of free triiodothyronine (T3):T4 (P<0.01). HOMA-ß had prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age, body mass index (BMI) and smoking. When analyzed by quartiles of FT4 or free T3:T4, there were significantly decreased trend of HOMA-ß going with the higher FT4 and lower free T3:T4 in both groups. Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-ß no matter in general population or T2DM patients, which was independent of age, BMI, smoking, hypertension and lipid profiles. FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects. Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

Shifts in the Bacterial Community of Supragingival Plaque Associated With Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD), also known as the hepatic manifestation of metabolic disorders, has become one of the most common chronic liver diseases worldwide. The associations between some oral resident microbes and MAFLD have been described. However, changes to the oral microbial community in patients with MAFLD remain unknown. In this study, variations to the supragingival microbiota of MAFLD patients were identified. The microbial genetic profile of supragingival plaque samples from 24 MAFLD patients and 22 healthy participants were analyzed by 16S rDNA sequencing and bioinformatics analysis. Clinical variables, including indicators of insulin resistance, obesity, blood lipids, and hepatocellular damage, were evaluated with laboratory tests and physical examinations. The results showed that the diversity of the supragingival microbiota in MAFLD patients was significantly higher than that in healthy individuals. Weighted UniFrac principal coordinates analysis and partial least squares discriminant analysis showed that the samples from the MAFLD and control groups formed separate clusters (Adonis, P = 0.0120). There were 27 taxa with differential distributions (linear discriminant analysis, LDA>2.0) between two groups, among which Actinomyces spp. and Prevotella 2 spp. were over-represented in the MAFLD group with highest LDA score, while Neisseria spp. and Bergeyella spp. were more abundant in the control group. Co-occurrence networks of the top 50 abundant genera in the two groups suggested that the inter-genera relationships were also altered in the supragingival plaque of MAFLD patients. In addition, in genus level, as risk factors for the development of MAFLD, insulin resistance was positively correlated with the abundances of Granulicatella, Veillonella, Streptococcus, and Scardovia, while obesity was positively correlated to the abundances of Streptococcus, Oslenella, Scardovia, and Selenomonas. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to sugar (mainly free sugar) metabolism were enriched in the supragingival plaque of the MAFLD group. In conclusion, as compared to healthy individuals, component and interactional dysbioses were observed in the supragingival microbiota of the MAFLD group.

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.

Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 5alpha-reductase inhibitor.

AIM: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5alpha-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. RESULTS: Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P < 0.01); DHT concentrations of group D rats were significantly decreased (P < 0.01) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. CONCLUSION: These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.

Investigation of iodine concentration in salt, water and soil along the coast of Zhejiang, China.

OBJECTIVE: We aim to describe the environment iodine concentration in salt, water and soil along Zhejiang Province coast in the China foreland. It will be helpful for us to judge whether this area is insufficient in iodine and universal iodized salt is necessary or not. METHODS: We collected iodized salt samples, drinking water samples (tap water in the towns, and well water or spring water in the villages), water samples from different sources (ditches, lakes, rivers) and soil samples through random sampling in June, 2005. Salt, water and soil iodine was detected by arsenic-cerium redox method. Statistical analysis was expressed as mean+/-SEM by Windows SPSS 13.0. RESULTS: (1) The iodine concentration in salt was 27.9+/-4.33 mg/kg (n=108). (2) Seventy-five water samples were collected. The water iodine value was 0.6-84.8 microg/L (mean of 11.66 mug/L). The watershed along the Qiantang River has significantly higher iodine content than the water in Lin'an in mountain area (P<0.01). The iodine content and mean iodine content of tap water, well or spring water and natural water sources were 4.30+/-2.43 microg/L (n=34), 23.59+/-27.74 microg/L (n=19) and 12.72+/-10.72 microg/L (n=22) respectively. This indicated that among environmental water sources, the ditch iodine content was the highest with river water iodine being the lowest (P<0.01). (3) Soil iodine value was 0.11-2.93 mg/kg (mean of 1.32 mg/kg). Though there was no statistical difference of soil iodine in different districts (P=0.131), soil iodine content correlated positively with water iodine content. CONCLUSION: Iodine concentration in salt accords with national policy of adding iodine in salt. Foreland has more iodine in water than mountain area. The data reflected that water and soil iodine in foreland area was not high, which suggests universal iodized salt should be necessary. Environment iodine has relatively close association with pollution.