Person:

Hu, Frank

OBJECTIVE: Accumulating evidence has identified a positive association between active smoking and the risk of diabetes, but previous studies had limited information on passive smoking or changes in smoking behaviors over time. This analysis examined the association between exposure to passive smoke, active smoking, and the risk of incident type 2 diabetes among women. RESEARCH DESIGN AND METHODS: This is a prospective cohort study of 100,526 women in the Nurses’ Health Study who did not have prevalent diabetes in 1982, with follow-up for diabetes for 24 years. RESULTS: We identified 5,392 incident cases of type 2 diabetes during 24 years of follow-up. Compared with nonsmokers with no exposure to passive smoke, there was an increased risk of diabetes among nonsmokers who were occasionally (relative risk [RR] 1.10 [95% CI 0.94–1.23]) or regularly (1.16 [1.00–1.35]) exposed to passive smoke. The risk of incident type 2 diabetes was increased by 28% (12–50) among all past smokers. The risk diminished as time since quitting increased but still was elevated even 20–29 years later (1.15 [1.00–1.32]). Current smokers had the highest risk of incident type 2 diabetes in a dose-dependent manner. Adjusted RRs increased from 1.39 (1.17–1.64) for 1–14 cigarettes per day to 1.98 (1.57–2.36) for ≥25 cigarettes per day compared with nonsmokers with no exposure to passive smoke. CONCLUSIONS: Our study suggests that exposure to passive smoke and active smoking are positively and independently associated with the risk of type 2 diabetes.

Background: Findings from observational studies suggest that sex hormone-binding globulin (SHBG) and endogenous sex hormones may be mediators of the putative relation between coffee consumption and lower risk of type 2 diabetes. The objective of this study was to evaluate the effects of caffeinated and decaffeinated coffee on SHBG and sex hormone levels. Findings: After a two-week run-in phase with caffeine abstention, we conducted an 8-week parallel-arm randomized controlled trial. Healthy adults (n = 42) were recruited from the Boston community who were regular coffee consumers, nonsmokers, and overweight. Participants were randomized to five 6-ounce cups of caffeinated or decaffeinated instant coffee or water (control group) per day consumed with each meal, mid-morning, and mid-afternoon. The main outcome measures were SHBG and sex hormones [i.e., testosterone, estradiol, dehydroepiandrosterone sulfate]. No significant differences were found between treatment groups for any of the studied outcomes at week 8. At 4 weeks, decaffeinated coffee was associated with a borderline significant increase in SHBG in women, but not in men. At week 4, we also observed several differences in hormone concentrations between the treatment groups. Among men, consumption of caffeinated coffee increased total testosterone and decreased total and free estradiol. Among women, decaffeinated coffee decreased total and free testosterone and caffeinated coffee decreased total testosterone. Conclusions: Our data do not indicate a consistent effect of caffeinated coffee consumption on SHBG in men or women, however results should be interpreted with caution given the small sample size. This is the first randomized trial investigating the effects of caffeinated and decaffeinated coffee on SHBG and sex hormones and our findings necessitate further examination in a larger intervention trial.

Objective: To 1) compare associations of diet-quality scores, which were inversely associated with cardiovascular disease, with incident type 2 diabetes and 2) test for differences in absolute-risk reduction across various strata. Research Design and Methods: Men from the Health Professionals Follow-Up Study, who were initially free of type 2 diabetes, cardiovascular disease, or cancer (n = 41,615), were followed for (\leq 20) years. The Healthy Eating Index (HEI) 2005, the alternative HEI (aHEI) the Recommended Food Score, the alternative Mediterranean Diet (aMED) Score, and the Dietary Approaches to Stop Hypertension (DASH) Score were calculated from food-frequency questionnaires. Cox proportional hazard models with time-varying covariates were used to assess risk by quintiles and continuous intervals. Results: There were 2,795 incident cases of type 2 diabetes. After multivariate adjustment, the aHEI, aMED, and DASH scores were significantly associated with reduced risk. A 1-SD increase was associated with 9–13% reduced risk (P < 0.01), and the DASH score was associated with lower risk independent of other scores. These scores were associated with lower absolute risk among those who were overweight or obese compared with normal weight (P for interaction < 0.01). Conclusions: Several diet-quality scores were associated with a lower risk of type 2 diabetes and reflect a common dietary pattern characterized by high intakes of plant-based foods such as whole grains; moderate alcohol; and low intakes of red and processed meat, sodium, sugar-sweetened beverages, and trans fat. High-quality diets may yield the greatest reduction in diabetes cases when followed by those with a high BMI.

OBJECTIVE: The objective of this study was to investigate the association of 4-year changes in alcohol consumption with a subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We prospectively examined 38,031 men from the Health Professionals Follow-Up Study who were free of diagnosed diabetes or cancer in 1990. Alcohol consumption was reported on food frequency questionnaires and updated every 4 years. RESULTS: A total of 1,905 cases of type 2 diabetes occurred during 428,497 person-years of follow-up. A 7.5 g/day (approximately half a glass) increase in alcohol consumption over 4 years was associated with lower diabetes risk among initial nondrinkers (multivariable hazard ratio [HR] 0.78; 95% CI: 0.60–1.00) and drinkers initially consuming <15 g/day (HR 0.89; 95% CI: 0.83–0.96), but not among men initially drinking ≥15 g/day (HR 0.99; 95% CI: 0.95–1.02; Pinteraction < 0.01). A similar pattern was observed for levels of total adiponectin and hemoglobin A1c, with a better metabolic profile among abstainers and light drinkers who modestly increased their alcohol intake, compared with men who either drank less or among men who were already moderate drinkers and increased their intake. Likewise, compared with stable light drinkers (0–4.9 g/day), light drinkers who increased their intake to moderate levels (5.0–29.9 g/day) had a significantly lower risk of type 2 diabetes (HR 0.75; 95% CI: 0.62–0.90). CONCLUSIONS: Increases in alcohol consumption over time were associated with lower risk of type 2 diabetes among initially rare and light drinkers. This lower risk was evident within a 4-year period following increased alcohol intake.

Hypertension and type 2 diabetes (T2D) commonly coexist, and both conditions are major risk factors for cardiovascular disease (CVD). We aimed to examine the association between genetic predisposition to high blood pressure and risk of CVD in individuals with T2D. The current study included 1,005 men and 1,299 women with T2D from the Health Professionals Follow-up Study and Nurses’ Health Study, of whom 732 developed CVD. A genetic predisposition score was calculated on the basis of 29 established blood pressure–associated variants. The genetic predisposition score showed consistent associations with risk of CVD in men and women. In the combined results, each additional blood pressure–increasing allele was associated with a 6% increased risk of CVD (odds ratio [OR] 1.06 [95% CI 1.03–1.10]). The OR was 1.62 (1.22–2.14) for risk of CVD comparing the extreme quartiles of the genetic predisposition score. The genetic association for CVD risk was significantly stronger in patients with T2D than that estimated in the general populations by a meta-analysis (OR per SD of genetic score 1.22 [95% CI 1.10–1.35] vs. 1.10 [1.08–1.12]; I2 = 71%). Our data indicate that genetic predisposition to high blood pressure is associated with an increased risk of CVD in individuals with T2D.

Background: Health concerns have been raised about rice consumption, which may significantly contribute to arsenic exposure. However, little is known regarding whether habitual rice consumption is associated with cardiovascular disease (CVD) risk. Objective: We examined prospectively the association of white rice and brown rice consumption with CVD risk. Design: We followed a total of 207,556 women and men [73,228 women from the Nurses’ Health Study (1984–2010), 92,158 women from the Nurses’ Health Study II (1991–2011), and 42,170 men from the Health Professionals Follow-Up Study (1986–2010)] who were free of CVD and cancer at baseline. Validated semiquantitative food-frequency questionnaires were used to assess consumption of white rice, brown rice, and other food items. Fatal and nonfatal CVD (coronary artery disease and stroke) was confirmed by medical records or self-reports. Results: During 4,393,130 person-years of follow-up, 12,391 cases of CVD were identified. After adjustment for major CVD risk factors, including demographics, lifestyle, and other dietary intakes, rice consumption was not associated with CVD risk. The multivariable-adjuted HR of developing CVD comparing ≥5 servings/wk with <1 serving/wk was 0.98 (95% CI: 0.84, 1.14) for white rice, 1.01 (0.79, 1.28) for brown rice, and 0.99 (0.90, 1.08) for total rice. To minimize the potential impact of racial difference in rice consumption, we restricted the analyses to whites only and obtained similar results: the HRs of CVD for ≥5 servings/wk compared with <1 serving/wk were 1.04 (95% CI: 0.88, 1.22) for white rice and 1.01 (0.78, 1.31) for brown rice. Conclusions: Greater habitual consumption of white rice or brown rice is not associated with CVD risk. These findings suggest that rice consumption may not pose a significant CVD risk among the U.S. population when consumed at current amounts. More prospective studies are needed to explore these associations in other populations.

Objective: Many confirmed genetic loci for obesity are expressed in regions of the brain that regulate energy intake and reward-seeking behavior. Whether these loci contribute to the development of specific eating behaviors has not been investigated. We examined the relationship between a genetic susceptibility to obesity and cognitive restraint, uncontrolled and emotional eating. Design and Methods Eating behavior and body mass index (BMI) were determined by questionnaires for 1471 men and 2381 women from two U.S cohorts. Genotypes were extracted from genome-wide scans and a genetic-risk score (GRS) derived from 32 obesity-loci was calculated. Results: The GRS was positively associated with emotional and uncontrolled eating(P<0.002). In exploratory analysis, BMI-increasing variants of MTCH2, TNNI3K and ZC3H4 were positively associated with emotional eating and those of TNNI3K and ZC3H4 were positively associated with uncontrolled eating. The BMI-increasing variant of FTO was positively and those of LRP1B and TFAP2B were inversely associated with cognitive restraint. These associations for single SNPs were independent of BMI but were not significant after multiple-testing correction. Conclusions: An overall genetic susceptibility to obesity may also extend to eating behaviors. The link between specific loci and obesity may be mediated by eating behavior but larger studies are warranted to confirm these results.

Primary open angle glaucoma (POAG) is a leading cause of blindness world-wide. To identify new susceptibility loci, we meta-analyzed GWAS results from 8 independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significant SNPs in two Australian studies (1,252 cases and 2,592 controls), 3 European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of top SNPs identified three novel loci: rs35934224[T] within TXNRD2 (odds ratio (OR) = 0.78, P = 4.05×10−11 encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] within ATXN2 (OR = 1.17, P = 8.73×10−10), and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76×10−10). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest novel targets for preventative therapies.

Background: Plant-based diets have been recommended to reduce the risk of type 2 diabetes (T2D). However, not all plant foods are necessarily beneficial. We examined the association of an overall plant-based diet and hypothesized healthful and unhealthful versions of a plant-based diet with T2D incidence in three prospective cohort studies in the US. Methods and Findings: We included 69,949 women from the Nurses’ Health Study (1984–2012), 90,239 women from the Nurses’ Health Study 2 (1991–2011), and 40,539 men from the Health Professionals Follow-Up Study (1986–2010), free of chronic diseases at baseline. Dietary data were collected every 2–4 y using a semi-quantitative food frequency questionnaire. Using these data, we created an overall plant-based diet index (PDI), where plant foods received positive scores, while animal foods (animal fats, dairy, eggs, fish/seafood, poultry/red meat, miscellaneous animal-based foods) received reverse scores. We also created a healthful plant-based diet index (hPDI), where healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, tea/coffee) received positive scores, while less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, sweets/desserts) and animal foods received reverse scores. Lastly, we created an unhealthful plant-based diet index (uPDI) by assigning positive scores to less healthy plant foods and reverse scores to healthy plant foods and animal foods. We documented 16,162 incident T2D cases during 4,102,369 person-years of follow-up. In pooled multivariable-adjusted analysis, both PDI and hPDI were inversely associated with T2D (PDI: hazard ratio [HR] for extreme deciles 0.51, 95% CI 0.47–0.55, p trend < 0.001; hPDI: HR for extreme deciles 0.55, 95% CI 0.51–0.59, p trend < 0.001). The association of T2D with PDI was considerably attenuated when we additionally adjusted for body mass index (BMI) categories (HR 0.80, 95% CI 0.74–0.87, p trend < 0.001), while that with hPDI remained largely unchanged (HR 0.66, 95% CI 0.61–0.72, p trend < 0.001). uPDI was positively associated with T2D even after BMI adjustment (HR for extreme deciles 1.16, 95% CI 1.08–1.25, p trend < 0.001). Limitations of the study include self-reported diet assessment, with the possibility of measurement error, and the potential for residual or unmeasured confounding given the observational nature of the study design. Conclusions: Our study suggests that plant-based diets, especially when rich in high-quality plant foods, are associated with substantially lower risk of developing T2D. This supports current recommendations to shift to diets rich in healthy plant foods, with lower intake of less healthy plant and animal foods.

Background: Hemoglobin A1c (HbA1c), a time‐integrated marker of glycemic control, predicts risk of coronary heart disease (CHD) among diabetics. Few studies have examined HbA1c and risk of CHD among women and men without clinically elevated levels or previously diagnosed diabetes. Methods and Results: We conducted parallel nested case–control studies among women (Nurses' Health Study) and men (Health Professionals Follow‐up Study). During 14 and 10 years of follow‐up, 468 women and 454 men developed incident nonfatal myocardial infarction (MI) and fatal CHD. Controls were matched 2:1 based on age, smoking, and date of blood draw. For these analyses, participants with a history of diabetes or HbA1c levels ≥6.5% at baseline were excluded. Compared with HbA1c of 5.0% to <5.5%, those with an HbA1c of 6.0% to <6.5% had a multivariable‐adjusted relative risk (RR) of CHD of 1.90 (95% CI 1.11 to 3.25) in women and 1.81 (95% CI 1.09 to 3.03) in men. The pooled RR of CHD was 1.29 (95% CI 1.11 to 1.50) for every 0.5%‐increment increase in HbA1c levels and 1.67 (95% CI 1.23 to 2.25) for every 1%‐increment increase, with the risk plateauing around 5.0%. Furthermore, participants with HbA1c levels between 6.0% and <6.5% and C‐reactive protein levels >3.0 mg/L had a 2.5‐fold higher risk of CHD compared with participants in the lowest categories of both biomarkers. Conclusions: Our findings suggest that HbA1c is associated with CHD risk among apparently healthy, nondiabetic women and men and may be an important early clinical marker of disease risk.