T Cell Subsets are Associated with Clinical Activity and Efficacy of 4.5g Intravenous Glucocorticoid for Moderate-To-Severe Thyroid-Associated Ophthalmopathy.

BACKGROUND: Intravenous glucocorticoid (IVGC) remains the main treatment for moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, a substantial number (20-30%) of active moderate-to-severe TAO patients may not respond to IVGC. Some patients may have disease progression despite IVGC treatment or relapse after steroid withdrawal. OBJECTIVES: To analyze risk factors for clinical activity and predictive factors for clinical outcomes of 4.5 g IVGC therapy in patients with moderate-to-severe TAO. DESIGN AND METHODS: Our study was performed in two steps: step 1 involved 110 moderate-to-severe TAO patients and analyzed risk factors for TAO activity; step 2 involved 53 active moderate-to-severe TAO patients from step 1 who were treated with 4.5 g IVGC therapy and analyzed predictive factors for clinical outcomes of IVGC therapy. Multivariate logistic regression analysis was used to identify the independent predictors and establish the predictive model. RESULTS: Abnormal TRAb (OR = 4.717; P = 0.019) and the percentage of CD3+CD4+ T cell (OR = 1.092; P = 0.028) were independently associated with the activity of moderate-to-severe TAO patients. The pretreatment CAS-max in both eyes (OR = 7.221; P = 0.013) and the percentage of pretreatment CD3+T cell (OR = 0.718; P = 0.037) were independently associated with therapeutic efficacy. The pretreatment CAS-max in both eyes (OR = 156.53; P = 0.028) and the percentage of post-treatment CD3+T cell (OR = 0.554; P = 0.043) were independently associated with therapeutic efficacy. Besides, multivariable prediction models were established, which were better in the forecasting aspect than single-variable prediction models. CONCLUSIONS: Based on the findings of this study, we should monitor the peripheral blood T cell subsets for TAO, which could be helpful to timely judge the condition of clinical manifestation and effect of treatment for TAO patients. Multivariable prediction models have been established, which have great significance for clinical work.

Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study.

BACKGROUND: Low circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology. METHODS: Ten thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria. RESULTS: Lower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRSsynthesis determined increase of 25(OH) D levels. CONCLUSIONS: We found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings.

Age and gender-specific distribution of metabolic syndrome components in East China: role of hypertriglyceridemia in the SPECT-China study.

BACKGROUND: Chinese population are experiencing remarkably changes of economic and cultural environments. The present study was to examine the prevalence of metabolic syndrome (MetS) by age between genders and to investigate the current characteristics of MetS and its components in China. METHODS: SPECT-China is a population-based cross-sectional survey on Chinese adults aged ≥18 years in East China. A total of 10,441 Chinese residents participated in anthropometric and laboratory measurements. Of these, 9969 subjects (females, 5868) were eligible for the data analysis reported here. Estimates of the prevalence of MetS and its components were calculated. Presence of MetS was defined based on the IDF/AHA harmonized criteria. MetS z-score was calculated to evaluate the degree of total metabolic disorder. RESULTS: The age-standardized prevalence of the metabolic syndrome was 22.0% (21.9% in men and 22.0% in women). Unlike the continuous MetS rise with age in females, the MetS prevalence in males remained stable among 46-55, 56-65 and > 65 yrs. age groups (31.2%, 31.4%, 32.5%, p = 0.538). In the five components of MetS, contrary to the elevated BP and BG disorders, the frequency of TG disorders decreased with age in males (46.6%(46-55 yrs), 37.2% (56-65 yrs), 27.7%(> 65 yrs), p < 0.001). Multivariable logistic regression showed that in males, more TG disorders were associated with higher BMI, higher educational level and current nonsmoker. In the MetS subjects, the 3-factor combinations which included TG disorders decreased with age in both genders. The whole metabolic profile became better in older male MetS subjects, which was opposite to the female. CONCLUSION: Our results showed a distinct age-related prevalence of MetS between genders in dramatically changed China, in which the TG disorders played an important role. More targeted measures need to be taken to meet the serious challenges of metabolic diseases. TRIAL REGISTRATION: ChiCTR-ECS- 14005052 , Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China).

Are Thyroid Autoimmune Diseases Associated with Cardiometabolic Risks in a Population with Normal Thyroid-Stimulating Hormone?

BACKGROUND: The interrelation between thyroid autoimmunity and cardiovascular risks is complex and has not been confirmed. This study aimed at evaluating whether there exists a relationship between thyroid autoimmune diseases (AITDs) and cardiometabolic risks in a large population with normal thyroid-stimulating hormone (TSH) levels. METHODS: The data was obtained from a cross-sectional study (SPECT-China study). This study enrolled 9082 subjects (3948 males and 5134 females) above 18 years with normal TSH levels. AITD was defined according to the positivity of TPOAb and TgAb as well as thyroid ultrasonography (US) findings. RESULTS: After full adjustment, TPOAb and/or TgAb positivity (TPO/TgAb (+)) was significantly associated with higher BMI, waist circumference (WC), and HbA1c only in women (P = 0.004, 0.026 and 0.032, respectively), while both TPO/TgAb positivity and US positivity (TPO/TgAb (+) and US (+)) were positively associated with BMI and WC in both genders (P = 0.002 and 0.020 in men; P < 0.001and <0.001 in women). TPO/TgAb (+) and US (+) were positively associated with HOMA-IR in women (P = 0.021) as well. Binary logistic analysis showed that AITDs had increased risks of central obesity, hyperlipidemia, and metabolic syndrome only in women (all P < 0.05). Moreover, TPO/TgAb (+) and US (+) were associated with an increased risk of obesity for both genders (P = 0.014 in men and P = 0.006 in women). CONCLUSIONS: Thyroid autoimmunity was positively associated with HbA1c, HOMA-IR, obesity, central obesity, hyperlipidemia, and metabolic syndrome, especially in women. This highlighted that AITDs may be potential risk factors for cardiometabolic disorders even if one's TSH was within the reference range.

Blood lead level is associated with non-alcoholic fatty liver disease in the Yangtze River Delta region of China in the context of rapid urbanization.

BACKGROUND: China has undergone rapid urbanization in the past three decades. We aimed to report blood lead level (B-Pb) in the most rapidly urbanized Yangtze River Delta Region of China, and explore the association B-Pb and non-alcoholic fatty liver disease (NAFLD). METHODS: Our data source was the SPECT-China study. We enrolled 2011 subjects from 6 villages in the Yangtze River Delta Region. Lead was measured by atomic absorption spectrometry. According to abdominal ultrasound, residents were divided into normal and NAFLD groups. RESULTS: In total, 824 (41.0%) were diagnosed with NAFLD. Medians (interquartile range) of B-Pb were 5.29 µg/dL (3.60-7.28) [0.25 µmol/L (0.17-0.35)] for men and 4.49 µg/dL (2.97-6.59) [0.22 µmol/L (0.14-0.32)] for women. In both genders, the NAFLD group had significantly greater B-Pb than normal group (both P < 0.001). The prevalence of NAFLD significantly increased with increasing B-Pb quartiles in men (P for trend = 0.032) and women (P for trend = 0.001). Residents in Shanghai had significantly greater B-Pb (P < 0.001) and a higher prevalence of NAFLD (P < 0.001). Compared with women in the lowest quartile of BLL, OR of NAFLD in women in the highest quartile was 1.613 (95%CI 1.082-2.405) (P for trend = 0.019) after multivariable adjustment. In men, this association showed marginal significance (OR 2.168, 95%CI 0.989-4.750, P for trend = 0.063). CONCLUSION: B-Pb in Chinese residents in the Yangtze River Delta Region were much higher than in developed countries. Elevated B-Pb was associated with an increased risk of NAFLD, especially in women.

The Relationship between Vitamin D and Type 2 Diabetes Is Intriguing: Glimpses from the Spect-China Study.

OBJECTIVE: Vitamin D is a multifunctional vitamin for our body. Type 2 diabetes mellitus (T2DM) is a common metabolic disease. Whether T2DM affects the serum 25(OH)D level has not been reported. The objective of this study was to reveal the extent to which vitamin D is present in the population in East China and to explore the relationship between serum 25(OH)D and T2DM. METHODS: The cohort was selected based on a large investigation named Survey on Prevalence in East China including 12,702 participants aged 21-92 years old. All the participants completed the questionnaire and went through a physical examination. Fasting blood samples were collected to test serum 25(OH)D and other metabolism-related indicators. AVONA was used to test the significance of differences among groups. Multinomial logistic regression was used to assess the association of T2DM with serum 25(OH)D level. RESULTS: The overall percentage of vitamin D deficiency was 80.55% (male 74.1%, female 85.0%). Men with lower serum 25(OH)D level had high value in homeostasis model assessment of insulin resistance and HbA1c. The serum 25(OH)D level of those who were diagnosed with T2DM was higher than that in non-diabetics. The serum 25(OH)D level of pre-diabetes was the highest. T2DM patients trended to have higher serum 25(OH)D levels. CONCLUSION: Vitamin D deficiency is common among the people in East-China. T2DM patients had higher levels of serum 25(OH)D. The relationship between vitamin D and T2DM is intriguing. It seemed that vitamin D was either irrelevant directly to T2DM or resisted in T2DM patients.

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.

Effects of exenatide therapy on insulin resistance in the skeletal muscles of high-fat diet and low-dose streptozotocin-induced diabetic rats.

PURPOSE: The glucagon-like peptide (GLP)-1 agonist exenatide shows the same multiple effects on glucose homeostasis as native GLP-1, which can reduce blood glucose levels in individuals with type-2 diabetes mellitus (T2DM). However, its underlying action mechanism on glucose metabolism in the skeletal muscle of T2DM cases is unknown. We investigated the effects and action mechanisms of exenatide on insulin resistance (IR) in the skeletal muscle of high-fat diet and low-dose streptozotocin-induced T2DM rats. METHODS: Four groups of Sprague-Dawley rats were studied: non-T2DM (control, C); non-T2DM + exenatide (C + E); T2DM (D); and T2DM + exenatide (D + E). After eight weeks, isotope-tracer methodology was applied to measure the total rate of appearance (Ra) of glucose and glucose infusion rate (GIR) using a hyperinsulinemic-euglycemic clamp with 3-(3)H-glucose infusion. Glucose uptake in gastrocnemius muscles was determined by measuring 2-deoxy-D-(14)C-glucose radioactivity. Simultaneously, ultrastructural changes in the cells of gastrocnemius muscles were studied. RESULTS: In the D + E group, body weight and levels of fasting plasma glucose, triglyceride, total cholesterol, low-density lipoprotein and insulin were decreased significantly (p < 0.01) compared with the D group. The Ra of glucose (94.70 ± 13.46 versus 121.07 ± 16.55 µmol/kg/min) was decreased (p < 0.01), whereas the exogenous GIR (144.68 ± 11.03 versus 114.50 ± 9.40 µmol/kg/min) and glucose uptake in muscle (0.24 ± 0.02 versus 0.17 ± 0.02 µmol/g/min) were increased markedly (p < 0.01). Ultrastructural observations revealed that exenatide attenuated the effect of swollen mitochondrial and endoplasmic reticulum within the cells of the skeletal muscle of T2DM rats. CONCLUSIONS: These data suggest that exenatide can significantly improve insulin sensitivity in skeletal muscle by increasing glucose uptake in T2DM rats.

Castration-induced testosterone deficiency increases fasting glucose associated with hepatic and extra-hepatic insulin resistance in adult male rats.

BACKGROUND: Testosterone deficiency is associated with insulin resistance. However, how testosterone deficiency affects insulin actions remains unclear. The aim of this study was to investigate the influence of castration-induced testosterone deficiency on the metabolic kinetics of glucose and to evaluate the hepatic and extra-hepatic insulin sensitivity, in advanced-age male Sprague-Dawley (SD) rats. METHODS: Ten-week-old male SD rats were randomly divided into three groups: (1) a control group (n = 10) in which the rats underwent sham castration (2) a castrated group (TD group for testosterone deficiency, n = 10) in which the rats underwent bilateral orchidectomy surgery and (3) a castrated group given testosterone propionate via intraperitoneal injection (25 mg/kg/day) to supplement androgen (TD + TP group, n = 10). At ten weeks after castration in the noted groups, all rats were subjected to an oral glucose tolerance test (OGTT), a pyruvate tolerance test (PTT) and an insulin tolerance test (ITT). Twenty weeks following that treatment, all rats underwent a hyperinsulinemic-euglycemic clamp procedure in conjunction with isotope--labeled glucose and glycerol tracer infusions. The rate of appearance (Ra) of glucose, glycerol and gluconeogenesis (GNG), hepatic glucose production and the rate of glucose disappearance (Rd) were assessed. Glucose uptake was determined by measuring the 2-deoxy-D-14C-glucose in the gastrocnemius muscles. RESULTS: Ten weeks after castration in the TD group, the fasting blood glucose and insulin levels were significantly increased (p < 0.01), the glucose-- induced insulin secretion was impaired and ITT revealed a temporarily increased whole body insulin sensitivity compared with the control group; 30 weeks after castration, the Ra of glucose, Ra of glycerol, as well as the HGP and GNG were also increased (p < 0.01), while the exogenous glucose infusion rate and uptake glucose in the muscle markedly decreased (p < 0.01). CONCLUSIONS: Castration-induced testosterone deficiency primarily increases fasting blood glucose levels. The clamp experiments revealed a clear insulin resistance both at the hepatic and extra-hepatic levels.

Blood Lead Level Is Associated with Visceral Adipose Dysfunction in Patients with Type 2 Diabetes.

We aimed to explore whether an elevated blood lead level (BLL) is associated with visceral adipose dysfunction in patients with type 2 diabetes mellitus (T2DM). Four thousand one hundred and fourteen diabetic participants were enrolled from seven communities in Shanghai in 2018 in the cross-sectional METAL study. BLL was measured by graphite furnace atomic absorption spectrometry. Visceral adiposity index (VAI) and lipid accumulation product (LAP)were calculated by simple anthropometric and biochemical parameters. We found that medians (IQR) of BLL were 26.0 µg/L (18.0-37.0) for men and 25.0 µg/L (18.0-35.0) for women, respectively. In men, each doubling of BLL was associated with a 2.0% higher VAI (95% CI, 0.6 to 3.5%) and 1.8% higher LAP (95% CI, 0.2 to 3.3%) after full adjustment. Using the lowest BLL quartile as the referent group, significant positive trends were observed for BLL with VAI and LAP. In women, each doubling of BLL was associated with a 1.9% higher LAP (95% CI, 0.6 to 3.1%). Additionally, there was a marginally significant positive association between BLL and VAI, either using log2-transformed concentrations as continuous variables or categorized in quartiles. In conclusion, lead exposure is associated with visceral adipose dysfunction in patients with T2DM. Further prospective studies are warranted to confirm our findings.

Association of follicle-stimulating hormone with lipid profiles in older women: a cross-sectional SPECT-China study.

AIMS: Follicle-stimulating hormone (FSH) is associated with higher risks of metabolic syndrome and diabetes in menopausal women. We aimed to investigate whether FSH was associated with the lipid profile in women older than 55 years. DESIGN: The data were obtained from a cross-sectional study. PARTICIPANTS: Our data were from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (China, including Shanghai and Zhejiang, Jiangxi and Anhui provinces). A total of 1795 women older than 55 years were selected. METHODS: Morning serum sex hormones and lipid profiles were measured. Linear and logistic regression analyses were used to analyse the data. RESULTS: Lower FSH was associated with lower high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TG), total cholesterol (TC)/HDL-C ratio and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio (all p for trend <0.05) after adjusting for age and other sex hormones. After further adjustment for body mass index, diabetes and hypertension, the associations of FSH with the lipid profile weakened, but the associations of FSH quartiles with HDL-C and the TC/HDL-C ratio were still significant (both p for trend <0.05). Compared with women in the highest FSH quartile, the odds of low HDL-C (HDL-C<1.04 mmol/L) in women in the lowest FSH quartile were 5.25 (95% CI 1.60 to 17.26) (p for trend <0.05) in the fully adjusted model, and the odds of TC≥6.22 mmol/L, TGs≥2.26 mmol/L and LDL-C≥4.14 mmol/L were not significant. Luteinising hormone did not show a significant association with dyslipidaemia. CONCLUSION: Lower FSH was associated with a worse lipid profile in women older than 55. Diabetes, adiposity and hypertension mostly explained the association of FSH with TGs and the LDL-C/HDL-C ratio but only partially explained the associations of FSH with HDL-C and the TC/HDL-C ratio.

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.

Bidirectional Mendelian Randomization Analysis for Vitamin D and Thyroid Peroxidase Antibody.

Purpose: Whether Vitamin D deficiency or insufficiency is associated with thyroid autoimmunity was debated for long time. This study was still to explore the causal relationship of 25 (OH) D with a thyroid peroxidase antibody (TPOAb). Methods: The data were obtained from a cross-sectional study, SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. 10636 participants were finally included in this study. Genotyped four 25 (OH) D-related and four TPOAb-associated single nucleotide polymorphisms (SNPs) created their genetic risk scores (GRS). Bidirectional mendelian randomization (MR) analysis was used in this study. Results: 25 (OH) D GRS was significantly associated with 25 (OH) D (B -0.093, 95% CI -0.111, -0.074) and TPOAb level (B 0.067, 95% CI 0.002 to 0.132). TPOAb GRS was significantly associated with TPOAb concentration (B 0.345, 95% CI 0.135 to 0.556), but not 25 (OH) D (B -0.030, 95% CI -0.091 to 0.030). Using 25 (OH) D_GRS as instrumental variable in the MR analysis, a causal relationship of genetically determined 25 (OH) D with increased TPOAb concentration (B -0.720, 95% CI -1.429 to -0.012). No relation was found between genetically instrumented TPOAb and 25 (OH) D. Conclusion: A higher VD_GRS was associated with higher risk of increased TPOAb concentration, which supports a causal association between decreased vitamin D and increased concentration of TPOAb in an eastern Chinese population.

Influence of 4-week or 12-week glucocorticoid treatment on metabolic changes in patients with active moderate-to-severe thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is a serious, progressive, vision-threatening and difficult-to-treat organ-specific autoimmune disease. The course, therapeutic effects and prognosis of moderate to severe TAO vary greatly. High-dose intravenous glucocorticoid (IVGC) therapy is considered a first-line treatment for active moderate-to-severe TAO, but there is still insufficient evidence regarding the treatment duration. Long-term IVGC therapy can influence the metabolism of glucose, lipids, and bone. This study was designed to compare changes in metabolic and immunological indexes as well as the magnetic resonance imaging apparent diffusion coefficient (ADC) of the extraocular muscles after 4 and 12 weeks of IVGC therapy. Forty-eight patients with active moderate-to-severe TAO were included in this retrospective cohort study. Metabolism and immunological indexes were measured before and after therapy. The ADC and clinical activity score (CAS) were used to evaluate the efficacy of treatment in these patients. We found that the patients in the 12-week group had increased fasting plasma glucose (p = 0.004), glycated hemoglobin (p = 0.028), total cholesterol (p < 0.001), and low-density lipoprotein (p < 0.001) after therapy. The patients in both groups had reduced bone metabolism markers after therapy. Thyroid peroxidase antibody and thyrotropin receptor antibody levels decreased after treatment in both groups (p < 0.001). A significant decrease in thyroglobulin antibody levels was found in the 4-week group (p = 0.006). The change in the ADC was higher in the 4-week group than in the 12-week group (p = 0.014). However, there were no significant differences in CAS values between the two groups. Therefore, 4-week IVGC therapy was recommended for patients with TAO with glucose and lipid disorders.

Iodine nutrition status and its association with microvascular complications in urban dwellers with type 2 diabetes.

BACKGROUND: The principal function of iodine acts on thyroid function, but in recent years, the role of iodine deficiency in metabolism has also been gradually revealed. We aimed to investigate the current status of iodized salt consumption and urinary iodine concentration (UIC) in an urban Chinese population with type 2 diabetes, and to further explore whether UIC was associated with diabetic microvascular complications. METHODS: Four thousand five hundred fifty-nine subjects with diabetes from 7 communities in downtown Shanghai were enrolled in the cross-sectional Metal Study in 2018. UIC was detected using an inductively coupled plasma-mass spectrometer. Diabetic kidney disease (DKD) was defined as urinary albumin-to-creatinine ratio (UACR) > 30 mg/g or estimated glomerular filtration rate < 60 mL/min/1.73 m2. Diabetic retinopathy (DR) was evaluated by high-quality fundus photographs and was remotely read by ophthalmologist. RESULTS: The median UIC of subjects with diabetes was 115.4 µg/L (78.9-170.8) in downtown Shanghai. Among all the subjects, 52.7% consumed non-iodized salt and 40.4% were iodine deficient. Iodine deficiency (UIC < 100 µg/L) was associated with an increased odds of DKD (OR 1.17; 95%CI 1.01-1.37) after adjustment for age, sex, education, current smokers, BMI, HbA1c, duration of diabetes, dyslipidemia, thyroid-stimulating hormone and free thyroxine. No association was observed between UIC and DR after multivariable adjustment. CONCLUSIONS: A concerning number of subjects with diabetes consumed non-iodized salt and suffered from iodine deficiency in coastal regions of China. Low UIC might be a risk factor for DKD, which should be further confirmed by longitudinal prospective studies.

Trends in Bone Mineral Density, Osteoporosis, and Osteopenia Among U.S. Adults With Prediabetes, 2005-2014.

OBJECTIVE: We aimed to evaluate trends in bone mineral density (BMD) and the prevalence of osteoporosis/osteopenia in U.S. adults with prediabetes and normal glucose regulation (NGR) and further investigate the association among prediabetes, osteopenia/osteoporosis, and fracture. RESEARCH DESIGN AND METHODS: We collected and analyzed data from the U.S. National Health and Nutrition Examination Surveys during the period from 2005 to 2014. Femoral neck and lumbar spine BMD data were available for 5,310 adults with prediabetes and 5,162 adults with NGR >40 years old. RESULTS: A shift was observed toward a lower BMD and a higher prevalence of osteopenia/osteoporosis at the femoral neck and lumbar spine in U.S. adults >40 years old with prediabetes since 2005, especially in men <60 and women ≥60 years old. A shift toward a higher prevalence of osteopenia/osteoporosis at the femoral neck was also observed in adults >40 years old with NGR. Moreover, prediabetes was associated with a higher prevalence of hip fracture, although participants with prediabetes had higher BMD and a lower prevalence of osteopenia/osteoporosis at the femoral neck. CONCLUSIONS: There was a declining trend in BMD from 2005 to 2014 in U.S. adults >40 years old with prediabetes and NGR, and this trend was more significant in men <60 years old. Populations with prediabetes may be exposed to relatively higher BMD but a higher prevalence of fracture.

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.

Multiple pregnancies and the risk of diabetes mellitus in postmenopausal women.

OBJECTIVE: We aimed to investigate whether the number of pregnancies during childbearing age was associated with diabetes in postmenopausal women with no history of gestational diabetes. METHODS: Our data source was the continuous National Health and Nutrition Examination Survey 1999 to 2014. We selected 9,138 postmenopausal women over 40 years old who did not have a history of gestational diabetes during pregnancy. Logistic regression analyses were applied for the association of the number of pregnancies with diabetes. RESULTS: We found women with ≥4 pregnancies had significantly greater fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), 2-hour plasma glucose, and the Homeostatic Model Assessment of Insulin Resistance than those with two to three pregnancies (all P < 0.01). These women also had a significantly higher prevalence of diabetes (28.4% vs 20.7%; P < 0.001). Using the two to three pregnancies group as the reference, we observed a positive association of log-FPG and log-HbA1c with 4 or more pregnancies after adjustment for sociodemographic, lifestyle, and reproductive factors, and body mass index (both P < 0.05). Compared to women with two to three pregnancies, the odds ratios for diabetes were 1.31 (95% confidence interval [CI] 1.01-1.71) for women who never got pregnant and 1.28 (95% CI 1.10-1.48) for those with at least 4 pregnancies after multivariate adjustment. CONCLUSIONS: At least 4 pregnancies through childbearing age may be a potential risk factor for diabetes in postmenopausal women without a history of gestational diabetes.

Causal Link Between Vitamin D and Total Testosterone in Men: A Mendelian Randomization Analysis.

CONTEXT: Low circulating vitamin D levels have been associated with lower total testosterone levels. These epidemiological associations, if true, would have public health importance because vitamin D deficiency is common and correctable. We tested whether genetically lowered vitamin D levels were associated with lower total testosterone (T), using Mendelian randomization (MR) methodology. DESIGN AND SETTING: A total of 4254 men were enrolled from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) study, which was performed at 23 sites in eastern China during 2014 to 2016. Using four single-nucleotide polymorphisms strongly associated with 25-hydroxyvitamin D [25(OH)D] levels, we created a genetic risk score (GRS) as an instrumental variable to estimate the effect of genetically lowered 25(OH)D on total T. MAIN OUTCOME MEASURE: Total T was detected by chemiluminescence assay. RESULTS: Lower 25(OH)D levels were associated with lower total T (ß, 0.40; 95% CI, 0.23 to 0.58) after multivariable adjustment. Per-SD increase in the vitamin D GRS (VD_GRS) was significantly associated with 25(OH)D (ß, -1.64; 95% CI, -2.04 to -1.24) and with total T (ß, -0.19; 95% CI, -0.37 to -0.02). Using VD_GRS as the instrumental variable in the MR analysis, the causal regression coefficient of genetically determined per-SD increase for 25(OH)D on total T was 0.12 (95% CI, 0.02 to 0.22). CONCLUSION: We provide evidence for the biologically plausible causal effects of 25(OH)D on total T using MR analysis. Whether vitamin D supplementation can raise androgen levels merits further investigation in long-term, randomized controlled trials.