Person:

Li, Yanping

Objectives To prospectively assess the joint association of birth weight and established lifestyle risk factors in adulthood with incident type 2 diabetes and to quantitatively decompose the attributing effects to birth weight only, to adulthood lifestyle only, and to their interaction. Design: Prospective cohort study. Setting: Health Professionals Follow-up Study (1986-2010), Nurses’ Health Study (1980-2010), and Nurses’ Health Study II (1991-2011). Participants: 149 794 men and women without diabetes, cardiovascular disease, or cancer at baseline. Main outcome measure Incident cases of type 2 diabetes, identified through self report and validated by a supplementary questionnaire. Unhealthy lifestyle was defined on the basis of body mass index, smoking, physical activity, alcohol consumption, and the alternate healthy eating index. Results: During 20-30 years of follow-up, 11 709 new cases of type 2 diabetes were documented. The multivariate adjusted relative risk of type 2 diabetes was 1.45 (95% confidence interval 1.32 to 1.59) per kg lower birth weight and 2.10 (1.71 to 2.58) per unhealthy lifestyle factor. The relative risk of type 2 diabetes associated with a combination of per kg lower birth weight and per unhealthy lifestyle factor was 2.86 (2.26 to 3.63), which was more than the addition of the risk associated with each individual factor, indicating a significant interaction on an additive scale (P for interaction<0.001). The attributable proportions of joint effect were 22% (95% confidence interval 18.3% to 26.4%) to lower birth weight alone, 59% (57.1% to 61.5%) to unhealthy lifestyle alone, and 18% (13.9% to 21.3%) to their interaction. Conclusion: Most cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle, but simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases.

The first epigenome-wide association study of BMI identified DNA methylation at an HIF3A locus associated with BMI. We tested the hypothesis that DNA methylation variants are associated with BMI according to intake of B vitamins. In two large cohorts, we found significant interactions between the DNA methylation–associated HIF3A single nucleotide polymorphism (SNP) rs3826795 and intake of B vitamins on 10-year changes in BMI. The association between rs3826795 and BMI changes consistently increased across the tertiles of total vitamin B2 and B12 intake (all P for interaction <0.01). The differences in the BMI changes per increment of minor allele were −0.10 (SE 0.06), −0.01 (SE 0.06), and 0.12 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B2 intake and −0.10 (SE 0.06), −0.01 (SE 0.06), and 0.10 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B12 intake. In two independent cohorts, a DNA methylation variant in HIF3A was associated with BMI changes through interactions with total or supplemental vitamin B2, vitamin B12, and folate. These findings suggest a potential causal relation between DNA methylation and adiposity.

Background: Although the timing of menarche and menopause may be associated with cardiovascular disease (CVD), the entire reproductive life span has not been considered comprehensively as risk for CVD. We investigate the associations of reproductive life span duration and ages at menarche and menopause, induced by natural means or surgical bilateral oophorectomy, with incident CVD in women. Methods and Results: Prospective cohort study of 73 814 Nurses' Health Study following participants without CVD, defined as incident coronary heart disease or stroke, from 1980 through 2012. Duration of reproductive life span was generated by subtracting age at menarche from age at menopause. A shorter reproductive life span was associated with a higher risk of incident CVD after multivariable adjustment (relative risk, 1.32 [95% confidence interval, 1.16–1.49] comparing duration <30 with ≥42 years; P trend<0.0001). Early age at menopause was associated with higher multivariable‐adjusted CVD risk (1.32 [1.16–1.51] comparing age <40 with 50 to <55 years; P trend<0.0001), with excess risk for both natural and surgical menopause. Compared with women with menarche at 13 years, the multivariable‐adjusted CVD risk for early menarche at ≤10 years was 1.22 (1.09–1.36). The association between reproductive life span and CVD remained significant in sensitivity analyses excluding women who experienced extreme early age at menarche or who used hormone therapy. Conclusions: A shorter duration of reproductive life span is associated with a higher risk of CVD, which is likely driven by the timing of menopause induced either naturally or surgically. Extremely early age at menarche is also associated with a higher risk of CVD.

OBJECTIVE Recent public health recommendations emphasize adopting a healthful dietary pattern, but evidence is scarce on whether incremental diet quality changes have an impact on long-term diabetes prevention. We aim to evaluate diet quality changes during a 4-year period and subsequent 4-year type 2 diabetes incidence. RESEARCH DESIGN AND METHODS Participants of prospective cohorts, the Nurses’ Health Study (NHS), NHS II, and the Health Professionals Follow-up Study, who were free of diabetes at baseline (n = 124,607), were observed for ≥20 years. Diet quality, reflected by the Alternate Healthy Eating Index (AHEI) score, was assessed every 4 years to calculate changes. RESULTS We documented 9,361 cases of type 2 diabetes during 2,093,416 person-years of follow-up. A >10% decrease in AHEI score over 4 years was associated with a higher subsequent diabetes risk (pooled hazard ratio 1.34 [95% CI 1.23–1.46]) with multiple adjustment, whereas a >10% increase in AHEI score was associated with a lower risk (0.84 [0.78–0.90]). Greater improvement in diet quality was associated with lower diabetes risk across baseline diet quality status (P for trend ≤ 0.001 for low, medium, or high initial diet quality) and baseline BMI (P for trend ≤ 0.01 for BMI <25, 25–29, or 30 kg/m2). Changes in body weight explained 32% (95% CI 24–41) of the association between AHEI changes (per 10% increase) and diabetes risk. CONCLUSIONS Improvement in overall diet quality is associated with a lower risk of type 2 diabetes, whereas deterioration in diet quality is associated with a higher risk. The association between diet quality changes and diabetes risk is only partly explained by body weight changes.