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.

Liver ChREBP Protects Against Fructose-Induced Glycogenic Hepatotoxicity by Regulating L-Type Pyruvate Kinase.

Excessive fructose consumption is closely linked to the pathogenesis of metabolic disease. Carbohydrate response element-binding protein (ChREBP) is a transcription factor essential for fructose tolerance in mice. However, the functional significance of liver ChREBP in fructose metabolism remains unclear. Here, we show that liver ChREBP protects mice against fructose-induced hepatotoxicity by regulating liver glycogen metabolism and ATP homeostasis. Liver-specific ablation of ChREBP did not compromise fructose tolerance, but rather caused severe transaminitis and hepatomegaly with massive glycogen overload in mice fed a high-fructose diet, while no obvious inflammation, cell death, or fibrosis was detected in the liver. In addition, liver ATP contents were significantly decreased by ChREBP deficiency in the fed state, which was rendered more pronounced by fructose feeding. Mechanistically, liver contents of glucose-6-phosphate (G6P), an allosteric activator of glycogen synthase, were markedly increased in the absence of liver ChREBP, while fasting-induced glycogen breakdown was not compromised. Furthermore, hepatic overexpression of LPK, a ChREBP target gene in glycolysis, could effectively rescue glycogen overload and ATP reduction, as well as mitigate fructose-induced hepatotoxicity in ChREBP-deficient mice. Taken together, our findings establish a critical role of liver ChREBP in coping with hepatic fructose stress and protecting from hepatotoxicity by regulating LPK.

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.

Transdifferentiation of hepatic oval cells into pancreatic islet beta-cells.

Insulin production by beta-cells derived from hepatic oval cells is a promising new approach for the treatment of diabetes. Hepatic oval cells can be redirected to the beta-cell linage by an appropriate combination of high extracellular glucose, specific extracellular matrix proteins (laminin and fibronectin), cytokines (activin A), and the expression of several differentiation-related transcription factors (Pdx-1, Ngn-3, MafA). We explore the process of hepatic oval cell transdifferentiation into pancreatic islet beta-cells and the cellular signaling pathways involved.

Acute effects of different glycemic index diets on serum motilin, orexin and neuropeptide Y concentrations in healthy individuals.

AIM: To determine whether different glycemic index (GI) diets have different effects on the acute secretion of motilin, orexin and neuropeptide Y (NPY), regulators of food intake, energy homeostasis and glucose metabolism. METHODS: Fifty healthy volunteers were randomly assigned to two groups and were fed an isocaloric breakfast (464 kcal) containing high GI (HGI; GI=90) or low GI (LGI; GI=47) components. Serum motilin, orexin, and NPY concentrations were measured before (0 h) and 2h after the meal. RESULTS: The concentrations of motilin, orexin-A, NPY, C-peptide, and blood glucose at 0 h were similar in both groups of subjects. However, 2 h after breakfast, the serum motilin, NPY, C-peptide, and blood glucose concentrations were increased and orexin-A concentrations were decreased in both groups. The percentage changes from 0 to 2 h [(2-h value-0-h value)/baseline×100)] in motilin (27.72±2.46% vs. 20.95±2.06%, p=0.04) and orexin-A (9.15±2.06% vs. 3.49±1.67%, p=0.038) concentrations were significantly higher in the LGI group than in the HGI group. By contrast, the percentage changes in NPY (53.7±9.73% vs. 28.1±5.2%, p=0.026) and blood glucose (12.3±3.78% vs. 1.77±2.52%, p=0.025) concentrations were significantly greater in the HGI group than in the LGI group. Although C-peptide concentrations increased significantly after breakfast in both groups, the magnitude of the increase was similar (132.69±25.15% vs. 139.98±27.29%, p=0.845). Motilin and NPY concentrations were moderately positive correlated (r=0.410, p=0.042), while orexin-A and NPY concentrations were negatively correlated (r=-0.429, p=0.033) at 2h in the LGI group. CONCLUSIONS: A breakfast with a LGI reduced the secretion of orexin-A but significantly stimulated motilin secretion, without marked effects on the secretion of NPY. Therefore, consumption of a LGI diet may help to regulate food intake and energy expenditure in healthy individuals based on the changes in these hormones.

Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats.

BACKGROUND: There is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet. METHODS: Female Sprague-Dawley rats were divided into 3 groups: the control group(C), n = 10; the andronate-treated group (Andronate), n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks); and the andronate-treated and high-fat diet group (Andronate+HFD), n = 10. The rate of glucose appearance (Ra of glucose), gluconeogenesis (GNG), and the rate of glycerol appearance (Ra of glycerol) were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured. RESULTS: Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P < 0.05) but similar blood glucose concentrations. Of the two andronate-treated groups, the andronate+HFD group had the most serious insulin resistance (IR). Estrus cycles were completely acyclic, with polycystic ovaries and elevated serum lipid profiles in the andronate+HFD group (P < 0.05). Ra of glucose and GNG increased significantly in the andronate+HFD rats. However, the Ra of glycerol was similar in the three groups. CONCLUSIONS: Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.

Short reaction of C-peptide, glucagon-like peptide-1, ghrelin and endomorphin-1 for different style diet in type 2 diabetic patients.

BACKGROUND: Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 (GLP-1), ghrelin and endomorphin-1 (EM-1) to the eastern and western style meals in patients with type 2 diabetes mellitus. METHODS: The study enrolled 57 patients with type 2 diabetes (20 men and 37 women, mean age (67.05 ± 8.26) years). Eastern style meal (meal A) and western style meal (meal B) were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before (0 hour) and after (2 hours) each diet. RESULTS: The delta (2h - 0h) of C- peptide in meal A was significantly lower than that in meal B (P = 0.0004). C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A (P < 0.0001, < 0.0001, = 0.001, = 0.0004 respectively). Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A (P = 0.0005, 0.0079 respectively). Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B (r(A0h) = 0.7836, r(B0h) = 0.9368, r(A2h) = 0.7615, r(B2h) = 0.9409, r(A(2h-0h)) = 0.7531, r((2h-0h))B = 0.9980, respectively, P < 0.0001). CONCLUSION: Western style meal (high fat and protein food) could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones (GLP-1, ghrelin) and brain peptide (EM-1) at the first phase of digestion.

Peripheral endomorphin-1 levels are suppressed in diabetic patients.

BACKGROUND: Endomorphins are endogenous ligands selective for mu-opioid receptors, which have been reported to stimulate appetite and regulate glucose homeostasis. But there are no reports about changes in peripheral endomorphin-1 (EM-1) levels in diabetic patients. The aim of this study was to measure plasma EM-1 levels in fasting and postprandial conditions in diabetic patients. METHODS: After an overnight fast, 38 patients (mean age, 67+/-8 years; 17 males and 21 females) and 22 healthy volunteers (mean age, 64+/-9 years; 9 males and 13 females) received a standard breakfast meal with total energy content of 476.1kcal. Blood samples were drawn from each subject in heparinized tubes before breakfast and 2h postprandially. Plasma concentrations of EM-1 were measured by radioimmunoassay (RIA). RESULTS: Comparing with healthy volunteers, EM-1 levels were significantly lower in diabetic patients at both time-points (fasting: 48.38+/-14.13pg/ml vs. 72.71+/-19.62pg/ml, p<0.0001; postprandial: 39.80+/-12.28pg/ml vs. 62.93+/-21.95pg/ml, p=0.0001). When compared with fasting levels, the postprandial concentrations of EM-1 decreased in both diabetic patients, as well as healthy controls. The absolute value of decrease was not significantly different between the two groups. CONCLUSIONS: Peripheral EM-1 levels were suppressed in diabetic patients and the levels decreased postprandially in both diabetic and healthy volunteers. This implies that EM-1 concentration has correlation with the change in glucose level. Thus, EM-1 could play a role in energy metabolism.