Association between dinner timing and glucose metabolism in rural China: A large-scale cross-sectional study.

OBJECTIVES: Meal timing is a major risk factor for metabolic disease. The aim of this study was to assess the relationship between dinner timing and glucose metabolism in the rural Chinese population. METHODS: This cross-sectional study included 7701 participants from a Henan rural cohort study. Basic information was collected by in-person questionnaires. Multiple linear regression analysis was used to evaluate the relationship between dinner timing and fasting insulin (FINS), fasting plasma glucose (FPG), and homeostatic model assessment for insulin resistance (HOMA-IR). Restricted cubic spline was employed to investigate the dose-response relationship between dinner timing and FINS, FPG, and HOMA-IR. A generalized linear model was used to explore the interaction effect of age and dinner timing on FINS, FPG, and HOMA-IR. RESULTS: After adjusting for confounding factors, FINS concentration was reduced by 0.482 mmol/L (P < 0.001) for each hour delay in dinner timing. Furthermore, the HOMA-IR index decreased by 0.122 mmol/L for each hour delay. The results indicated a noticeable trend of decreasing values associated with later dinner timing (FINS: Poverall association < 0.001, Pnonlinear association = 0.144; HOMA-IR: Poverall association = 0.001, Pnonlinear association = 0.186). The interaction between age and dinner time significantly correlated with FINS and HOMA-IR (P < 0.05). This relationship was statistically significant before 69 y (P < 0.05). CONCLUSION: A significant association between dinner timing and glucose metabolism was observed in the rural Chinese population. Delayed dinner timing may be associated with lower fasting insulin. The negative effect of dinner timing on FINS and HOMA-IR was diminished with age.

Both early and late maternal age at childbirth is associated with increasing odds of central obesity in offspring.

OBJECTIVE: Despite studies on offspring obesity and delayed parenthood, little attention has been paid to the central obesity of offspring. The purpose of this study was to test the hypothesis that maternal age at childbirth (MAC) was associated with central obesity in offspring among the adult population, and fasting insulin may play a role in this association as a mediating factor. METHODS: A total of 423 adults (mean age 37.9 years, 37.1% female) were included. Information about maternal variables and other confounders was collected by face-to-face interview. Waist circumference and insulin were determined through physical measurements and biochemical examinations. Logistic regression model and restricted cubic spline model were used to analyze the relationship between MAC and central obesity of offspring. The mediating effect of fasting insulin levels on association between MAC and offspring waist circumference was also analyzed. RESULTS: There was a nonlinear relationship between MAC and central obesity in offspring. Compared with subjects with MAC 27-32 years, those with MAC 21-26 years (OR = 1.814, 95% CI: 1.129-2.915) and MAC ≥33 years (OR = 3.337, 95% CI: 1.638-6.798) had higher odds to develop central obesity. Offspring fasting insulin was also higher in MAC 21-26 years and MAC ≥33 years compared with those with MAC 27-32 years. Taking the group MAC 27-32 years as reference, the mediating effect of fasting insulin levels on the waist circumference was 20.6% and 12.4% for MAC 21-26 years and ≥ 33 years, respectively. CONCLUSION: MAC 27-32 years has the lowest odds of central obesity in offspring. Fasting insulin levels may have a partial mediating effect on the association between MAC and central obesity.

Evidence of a casual relationship between vitamin D deficiency and hypertension: a family-based study.

An association between vitamin D deficiency and hypertension has been observed in numerous studies. However, blood pressure improvements resulting from supplementation with vitamin D have been inconsistent. The causal relationship between vitamin D deficiency and hypertension is still unclear and was investigated in this family-based study. A total of 1370 individuals from both vitamin D deficiency and hypertension families were included. First, the heritability of vitamin D deficiency was estimated by the Falconer method. Second, SNPs (single nucleotide polymorphisms) of vitamin D metabolic and functional pathway genes associated with vitamin D deficiency were screened by a family-based association test, and the findings were further verified in nuclear families with vitamin D deficiency. Finally, a family-based association test was applied to investigate the association between selected SNPs associated with vitamin D deficiency and hypertension. The heritability of vitamin D deficiency was 50.4% in this family-based study. Allele C of rs3847987 was a risk factor for vitamin D deficiency (OR: 1.639, 95% CI: 1.170-2.297, P = 0.004). Furthermore, a family-based association of rs3847987 with hypertension was found in both additive and recessive models (P < 0.05). In addition, vitamin D deficiency was associated with hypertension (OR: 1.317, 95% CI: 1.022-1.698, P = 0.033). In conclusion, rs3847987 in the VDR gene was associated with both vitamin D deficiency and hypertension. Therefore, vitamin D deficiency may be a causal factor for hypertension.

A digital immuno-PCR assay for simultaneous determination of 5-methylcytosine and 5-hydroxymethylcytosine in human serum.

This work aimed to develop an ultrasensitive and specific immunosorbent assay for simultaneous detection of double DNA methylation marks. Being considered the most important indicators in disease diagnosis, clinical treatment, and prognosis, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) were chosen as the proof-of-concept targets. The described strategy consisted of Phos-tag Biotin anchoring at streptavidin-magnetic nanoparticles, specific immune recognition of anti-5mC antibody and anti-5hmC antibody and labeling of Barcode-antibody, signal amplification of immune PCR and digital PCR machine. Under optimal conditions, the digital immuno-PCR assay showed a board dynamic range from 2.7 × 10-13 mol/L to 2.7 × 10-9 mol/L and the detection limits were 61.7 fmol/L for 5mC, and of 0.111 pmol/L for 5hmC. A 16-fold and 186-fold improvement of LOD were obtained by the proposed approach for 5mC and 5hmC detection compared with real-time immune PCR. The approach also showed ideal specificity, repeatability and stability. The recovery test demonstrated that the digital immuno-PCR assay is a promising platform for the simultaneous determination of the two DNA methylation marks in human serum sample.

Vitamin D receptor methylation attenuates the association between physical activity and type 2 diabetes mellitus: A case-control study.

BACKGROUND: Physical activity and vitamin D receptor (VDR) have been associated with type 2 diabetes mellitus (T2DM). However, the associations of VDR methylation with T2DM and physical activity remained unknown. We aimed to investigate whether VDR methylation was a link between physical activity and T2DM. METHODS: A 1:1 matching case-control study was designed based on the Henan Rural Cohort Study, including 272 pairs of T2DM patients and nonpatients. Physical activity level was assessed using the International Physical Activity Questionnaire. The high-resolution melt method was applied to determine the methylation level of the promoter region of VDR. The association between physical activity and T2DM was analyzed with a conditional logistic regression model. The effect modification of VDR methylation levels on the association between physical activity and T2DM was conducted. A multivariate correlation analysis model was applied to investigate correlations of VDR methylation with insulin sensitivity. RESULTS: Physical activity level was associated with T2DM risk (crude model: odds ratio [OR] 0.611; 95% CI, 0.416-0.897; adjusted model: OR 0.619; 95% CI, 0.418-0.917). In effect modification analysis, the effects of physical activity on T2DM were stronger for low VDR methylation levels than for high (P = .025). Moreover, VDR methylation levels were associated with insulin (r = -0.089, P = .039) as well as homeostatic model assessment of insulin resistance (r = -0.098, P = .022). CONCLUSIONS: The methylation status of the VDR promoter is associated with the secretion and sensitivity of insulin. VDR methylation attenuates the association between physical activity and T2DM, indicating that proactively physical activity may reduce the risk of T2DM, especially in people with low VDR methylation level.

Heritability Estimation and Environmental Risk Assessment for Type 2 Diabetes Mellitus in a Rural Region in Henan, China: Family-Based and Case-Control Studies.

Objective: The prevalence of type 2 diabetes mellitus (T2DM) varies greatly in different regions and populations. This study aims to assess the heritability and environmental risk factors of T2DM among rural Chinese adults. Methods: Thousand five hundred thirty three participants from 499 extended families, which included 24 nuclear families, were recruited in the family-based study to assess the heritable risk of T2DM. Heritability of T2DM was estimated by the Falconer method. Using conditional logistic regression model, couple case-control study involving 127 couples were applied to assess the environmental risk factors of T2DM. Results: Compared with the Henan Rural Cohort, T2DM was significantly clustered in the nuclear families (OR: 8.389, 95% CI: 5.537-12.711, P < 0.001) and heritability was 0.74. No association between the heredity of T2DM and sex was observed between the extended families and the Henan Rural Cohort. Besides, results from the couple case-control study showed that physical activity (OR: 0.482, 95% CI: 0.261-0.893, P = 0.020) and fat intake (OR: 3.036, 95% CI: 1.070-8.610, P = 0.037) was associated with T2DM, and the proportion of offspring engaged in medium and high physical activity was higher than that of mothers in mother-offspring pairs. Conclusion: People with a family history of T2DM may have a higher risk of developing T2DM, however, there was no difference in genetic risk between males and females. Adherence to active physical activity and low fat intake can reduce the risk of T2DM.

CYP27B1 as an instrument gene to investigate the causal relationship between vitamin D deficiency and obesity: a family-based study.

OBJECTIVES: Vitamin D deficiency was associated with obesity. However, the causal relationship remains controversial. We hypothesized that there would be family-based associations in both vitamin D deficient families and obese families for the SNPs associated with vitamin D deficiency, if vitamin D deficiency was a causal factor of obesity. We aimed to investigate the family-based association of SNPs in CYP27B1 with both vitamin D deficiency and obesity. METHODS: Four hundred and nineteen pedigrees containing 1505 rural individuals aged from 18 to 79 years in Henan Province of China were included in this study. Family-based associations of rs10877012 and rs4646536 in CYP27B1 with vitamin D deficiency and obesity were investigated. Serum 25(OH)D3 concentration <20 µg/L was defined as vitamin D deficiency. BMI ≥ 28 kg/m2 was applied for obesity definition. Taqman assays were applied for SNP genotyping. Family-based associations were investigated with FBAT software. RESULTS: It was shown that vitamin D deficiency was a risk factor of obesity (adjusted OR: 1.332, 95% CI: 1.042-1.703, P = 0.022). Furthermore, there were family-based associations for allele T of rs10877012 and allele T of rs4646536 in both vitamin D deficient families and obese families (P < 0.05). Both rs10877012 and rs4646536 were associated with serum 25(OH)D3 levels between siblings (P < 0.05), but not BMI (P > 0.05). In addition, there is linkage disequilibrium between rs10877012 and rs4646536 (D' = 1.0, r2 = 0.992). CONCLUSION: Vitamin D deficiency may be a causal factor of obesity. Maintaining sufficient vitamin D is beneficial to obesity prevention.