Dongping Lin

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

Blood lead level and its association with body mass index and obesity in China - Results from SPECT-China study

28 in 1978 to

Visceral fat dysfunction is positively associated with hypogonadism in Chinese men.

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.

Chemokine (C-C Motif) Ligand 20, a Potential Biomarker for Graves' Disease, Is Regulated by Osteopontin

We aimed to report environmental and blood lead level (BLL) in China, and investigate the relationship of BLL with body mass index (BMI) and obesity. 5558 subjects were enrolled from 16 sites in China. BLL was measured by atomic absorption spectrometry. Obesity was defined as BMI ≥ 30 kg/m2. Median (interquartile range) of BLL was 44.00 μg/L (29.00–62.16) for men and 37.79 μg/L (25.13–54.35) for women, about twice higher than in U.S. population. Subjects in rural and high-economic-status areas had significantly greater BLL (P < 0.001). However, in these areas, the lead levels in drinking water, river water and rice were comparable to or significantly lower than those in urban and low-economic-status areas. After adjustment for age, urbanization, economic status and metabolic factors, BLL was independently associated with BMI in women (P for trend < 0.001), but not in men. In fully adjusted model, increased quartiles of BLL were associated with significantly increased odds ratios of obesity (P for trend < 0.01) in women. In conclusion, BLLs in Chinese adults were much higher than in developed countries. There was a sex-specific association between BLL and BMI. Elevated BLL does not appear to be associated with lead levels in drinking water or rice, suggesting some other exposure source.

Follicle‐stimulating hormone is associated with non‐alcoholic fatty liver disease in Chinese women over 55 years old

Visceral adiposity index (VAI) well mirrors visceral fat dysfunction. No study explored the association between low androgen and VAI. We aimed to determine whether VAI was associated with hypogonadism and sex hormones, and also whether it better predicted hypogonadism than other obesity indices. Our data were collected from 16 sites in East China. 2,759 men were enrolled. Hypogonadism was defined as total testosterone < 11.3 nmol/L. VAI was calculated in male: (waist circumference/(39.68 + (1.88 × BMI))) × (triglycerides/1.03) × (1.31/HDL). 484 (17.5%) hypogonadal men had significantly higher VAI. After adjusting for age, smoking, neck and hip circumference, diabetes and hypertension, VAI was inversely associated with total testosterone, estradiol and SHBG (P < 0.01). Higher quartiles of VAI were associated with significantly increasing odds of hypogonadism (P for trend < 0.01). The fully adjusted odds ratio was 5.88 (95 CI% 4.09, 8.46) for the highest quartile compared with the lowest quartile of VAI. Among all the indices investigated, VAI showed the largest area under the curve (P < 0.001). In conclusion, the VAI was significantly associated with a higher prevalence of hypogonadism in Chinese men. VAI also best predicted hypogonadism among obesity indices (waist, hip and neck circumference, BMI, waist-hip ratio and body adiposity index).

Increased chemokine (C–C motif) ligand 21 expression and its correlation with osteopontin in Graves’ disease

Context Graves’ disease (GD) is a common autoimmune disease involving the thyroid gland. The altered balance of pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of GD. Chemokine (C-C motif) ligand 20 (CCL20) is important for interleukin-17 (IL-17) signal activation and a potent chemoattractant for Th17 cells. Meanwhile, Osteopontin (OPN), a broadly expressed pleiotropic cytokine, has been implicated in GD through inducing Th1-involved response to enhance the production of proinflammatory cytokines and chemokines, but little is known about the role of OPN in regulating CCL20 and IL-17 signaling. Objective This study sought to explore the possibility of CCL20 level as a biomarker for GD, as well as investigate the role of OPN in regulating CCL20 production. Methods Fifty untreated GD patients, fifteen euthyroid GD patients, twelve TRAb-negative GD patients and thirty-five healthy control donors were recruited. OPN, CCL20 and other clinical GD diagnosis parameters were measured. CD4+T cells were isolated from peripheral blood mononuclear cells (PBMCs) using antibody-coated magnetic beads. Enzyme-linked immune-sorbent assay and quantitative polymerase chain reaction were used to determine CCL20 expression level. Results We found that the plasma CCL20 level was enhanced in GD patients and decreased in euthyroid and TRAb-negative GD patients. In addition, CCL20 level correlated with GD clinical diagnostic parameters and plasma OPN level. Moreover, we demonstrated that recombinant OPN and plasma from untreated GD patients increased the expression of CCL20 in CD4+T cells, which could be blocked by OPN antibody. Furthermore, we found that the effect of OPN on CCL20 expression was mediated by β3 integrin receptor, IL-17, NF-κB and MAPK pathways. Conclusions These results demonstrated that CCL20 might serve as a biomarker for GD and suggested the possible role of OPN in induction of CCL20 expression.

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

Obesity and diabetes are related to non‐alcoholic fatty liver disease (NAFLD). A reduction in follicle‐stimulating hormone (FSH) is associated with obesity and diabetes in postmenopausal women. Thus, we aim to investigate whether FSH is associated with NAFLD in women over 55 who were postmenopausal with a high probability.

MicroRNA-4443 Causes CD4+ T Cells Dysfunction by Targeting TNFR-Associated Factor 4 in Graves’ Disease

Graves’ disease (GD) is a chronic autoimmune process characterized by the production of auto-antibodies that presumably consequent to the lymphocytic infiltrates in the thyroid. Chemokine (C–C motif) ligand 21 (CCL21) is important for the circulation of CC-chemokine receptor 7 (CCR7)-expressing cells. Meanwhile, osteopontin (OPN) enhances the production of proinflammatory cytokines and chemokines through NF-κB and MAPK signaling pathways in GD. Although CCL21 has been reported to play a vital role in several autoimmune diseases, little is known about the relationship between CCL21 and GD development. This study aimed to detect the CCL21 level in GD and to examine the role of OPN in regulating CCL21 production. 40 initial GD patients, 15 euthyroid GD patients, 12 TRAb-negative GD patients, and 25 healthy control donors were recruited. CCL21 levels in plasma and culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). CD4+ T cells were isolated from peripheral blood mononuclear cells using antibody-coated magnetic beads. Quantitative polymerase chain reaction was used to determine CCL21 expression levels in CD4+ T cells. We demonstrated for the first time that plasma CCL21 levels were overexpressed in GD patients and recovered in TRAb-negative GD patients. Moreover, CCL21 levels correlated with TRAb levels and plasma OPN concentrations. Furthermore, we demonstrated that recombinant OPN increased the expression of CCL21 in a dose- and time-dependent manner. These data indicated a clinical correlation between plasma CCL21 levels and GD. CCL21 could serve as a novel biomarker for GD as well as a potential target for TRAb-positive GD treatment.

Type 2 Diabetes and Adiposity Induce Different Lipid Profile Disorders: A Mendelian Randomization Analysis

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 (β) 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 (β = -0.272/year, p < 0.001). E2 and SHBG increased with age (β = 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 (β = -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.

Low Sex Hormone-Binding Globulin Levels Associate with Prediabetes in Chinese Men Independent of Total Testosterone.

Context Aberrant CD4+ T cell function plays a critical role in the process of Graves’ disease (GD). MicroRNAs (miRNAs) are important regulators of T cell activation, proliferation, and cytokine production. However, the contribution of miRNAs to CD4+ T cell dysfunction in GD remains unclear. Objective To investigate how certain miRNA causes aberrant CD4+ T cell function in GD patients. Methods We compared the expression pattern of miRNAs in CD4+ T cells from untreated GD (UGD) patients with those from healthy controls. The most significantly dysregulated miRNAs were selected and their correlations with clinical parameters were analyzed. The effect of miR-4443 on CD4+ T cells cytokines production and proliferation was assessed. The potential gene target was identified and validated. Results GD patients had unique pattern of miRNA expression profile in CD4+ T cells comparing to healthy subjects. miR-10a, miR-125b, and miR-4443 were the three most significantly dysregulated miRNAs. The elevated miR-4443 levels were strongly correlated with clinical parameters in an independent dataset of UGD patients (N = 40), while miR-4443 was normally expressed in GD patients with euthyroidism and negative TRAb level. We found that miR-4443 directly inhibited TNFR-associated factor (TRAF) 4 expression to increase CD4+ T cells cytokines secretion as well as proliferation through the NF-κB pathway. Furthermore, the TRAF4 levels in GD patients were inversely correlated with miR-4443, and knocking down TRAF4 had a similar effect with miR-4443 overexpression. Conclusion The increased expression of miR-4443 induced CD4+ T cells dysfunction by targeting TRAF4, which may cause GD.