Showing papers by "Frank B. Hu published in 2008"

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Abstract: Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.

Short Sleep Duration and Weight Gain : A Systematic Review

Abstract: Objective The recent obesity epidemic has been accompanied by a parallel growth in chronic sleep deprivation. Physiologic studies suggest sleep deprivation may influence weight through effects on appetite, physical activity, and/or thermoregulation. This work reviews the literature regarding short sleep duration as an independent risk factor for obesity and weight gain.

Adherence to a DASH-style diet and risk of coronary heart disease and stroke in women.

Abstract: Background: The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to lower blood pressure, but little is known about its long-term effect on cardiovascular end points. Our objective was to assess the association between a DASH-style diet adherence score and risk of coronary heart disease (CHD) and stroke in women. Methods: In this prospective cohort study, diet was assessed 7 times during 24 years of follow-up (19802004) with validated food frequency questionnaires. A DASH score based on 8 food and nutrient components (fruits, vegetables, whole grains, nuts and legumes, lowfat dairy, red and processed meats, sweetened beverages, and sodium) was calculated. Lifestyle and medical information was collected biennially with a questionnaire. The Cox proportional hazard model was used to adjust for potential confounders. The study population comprised 88 517 female nurses aged 34 to 59 years without a history of cardiovascular disease or diabetes in 1980. The main outcome measures were the numbers of confirmed incident cases of nonfatal myocardial infarction, CHD death, and stroke. Results: We documented 2129 cases of incident nonfatal myocardial infarction, 976 CHD deaths, and 3105 cases of stroke. After adjustment for age, smoking, and other cardiovascular risk factors, the relative risks of CHD across quintiles of the DASH score were 1.0, 0.99, 0.86, 0.87, and 0.76 (95% confidence interval, 0.67-0.85) (P.001 for trend). The magnitude of risk difference was similar for nonfatal myocardial infarction and fatal CHD. The DASH score was also significantly associated with lower risk of stroke (multivariate relative risks across quintiles of the DASH score were 1.0, 0.92, 0.91, 0.89, and 0.82) (P=.002 for trend). Cross-sectional analysis in a subgroup of women with blood samples showed that the DASH score was significantly associated with lower plasma levels of C-reactive protein (P=.008 for trend) and interleukin 6 (P=.04 for trend). Conclusion: Adherence to the DASH-style diet is associated with a lower risk of CHD and stroke among middleaged women during 24 years of follow-up.

Abdominal Obesity and the Risk of All-Cause, Cardiovascular, and Cancer Mortality Sixteen Years of Follow-Up in US Women

Abstract: Background— Accumulating evidence indicates that abdominal adiposity is positively related to cardiovascular disease (CVD) risk and some other diseases independently of overall adiposity. However, the association of premature death resulting from these diseases with abdominal adiposity has not been widely studied, and findings are inconsistent. Methods and Results— In a prospective cohort study of 44 636 women in the Nurses’ Health Study, associations of abdominal adiposity with all-cause and cause-specific mortality were examined. During 16 years of follow-up, 3507 deaths were identified, including 751 cardiovascular deaths and 1748 cancer deaths. After adjustment for body mass index and potential confounders, the relative risks across the lowest to the highest waist circumference quintiles were 1.00, 1.11, 1.17, 1.31, and 1.79 (95% confidence interval [CI], 1.47 to 1.98) for all-cause mortality; 1.00, 1.04, 1.04, 1.28, and 1.99 (95% CI, 1.44 to 2.73) for CVD mortality; and 1.00, 1.18, 1.20, 1.34, and 1....

Identification of ten loci associated with height highlights new biological pathways in human growth.

Abstract: Identification of ten loci associated with height highlights new biological pathways in human growth

Dietary Patterns and Risk of Mortality From Cardiovascular Disease, Cancer, and All Causes in a Prospective Cohort of Women

Abstract: Background— The impact of overall dietary patterns that reflect actual eating behaviors on mortality caused by cardiovascular or other chronic diseases is largely unknown. Methods and Results— We p...

A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.

Abstract: We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0×10−62 and p = 7.46×10−127, respectively. The IRF4 SNP was also associated with skin color (p = 6.2×10−14), eye color (p = 6.1×10−13), and skin tanning response to sunlight (p = 3.9×10−89). A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52). One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation.

Combined impact of lifestyle factors on mortality: prospective cohort study in US women

Abstract: Objective To evaluate the impact of combinations of lifestyle factors on mortality in middle aged women. Design Prospective cohort study. Setting Nurses’ health study, United States. Participants 77 782 women aged 34 to 59 years and free from cardiovascular disease and cancer in 1980. Main outcome measure Relative risk of mortality during 24 years of follow-up in relation to five lifestyle factors (cigarette smoking, being overweight, taking little moderate to vigorous physical activity, no light to moderate alcohol intake, and low diet quality score). Results 8882 deaths were documented, including 1790 from cardiovascular disease and 4527 from cancer. Each lifestyle factor independently and significantly predicted mortality. Relative risks for five compared with zero lifestyle risk factors were 3.26 (95% confidence interval 2.45 to 4.34) for cancer mortality, 8.17 (4.96 to 13.47) for cardiovascular mortality, and 4.31 (3.51 to 5.31) for all cause mortality. A total of 28% (25% to 31%) of deaths during follow-up could be attributed to smoking and 55% (47% to 62%) to the combination of smoking, being overweight, lack of physical activity, and a low diet quality. Additionally considering alcohol intake did not substantially change this estimate. Conclusions These results indicate that adherence to lifestyle guidelines is associated with markedly lower mortality in middle aged women. Both efforts to eradicate cigarette smoking and those to stimulate regular physical activity and a healthy diet should be intensified.

Intake of fruit, vegetables, and fruit juices and risk of diabetes in women.

Abstract: OBJECTIVE—The purpose of this study was to examine the association between fruit, vegetable, and fruit juice intake and development of type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 71,346 female nurses aged 38–63 years who were free of cardiovascular disease, cancer, and diabetes in 1984 were followed for 18 years, and dietary information was collected using a semiquantitative food frequency questionnaire every 4 years. Diagnosis of diabetes was self-reported. RESULTS—During follow-up, 4,529 cases of diabetes were documented, and the cumulative incidence of diabetes was 7.4%. An increase of three servings/day in total fruit and vegetable consumption was not associated with development of diabetes (multivariate-adjusted hazard ratio 0.99 [95% CI 0.94–1.05]), whereas the same increase in whole fruit consumption was associated with a lower hazard of diabetes (0.82 [0.72–0.94]). An increase of 1 serving/day in green leafy vegetable consumption was associated with a modestly lower hazard of diabetes (0.91 [0.84–0.98]), whereas the same change in fruit juice intake was associated with an increased hazard of diabetes (1.18 [1.10–1.26]). CONCLUSIONS—Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women.

The Role of Tree Nuts and Peanuts in the Prevention of Coronary Heart Disease: Multiple Potential Mechanisms

Abstract: Epidemiologic and clinical trial evidence has demonstrated consistent benefits of nut and peanut consumption on coronary heart disease (CHD) risk and associated risk factors. The epidemiologic studies have reported various endpoints, including fatal CHD, total CHD death, total CHD, and nonfatal myocardial infarct. A pooled analysis of 4 U.S. epidemiologic studies showed that subjects in the highest intake group for nut consumption had an approximately 35% reduced risk of CHD incidence. The reduction in total CHD death was due primarily to a decrease in sudden cardiac death. Clinical studies have evaluated the effects of many different nuts and peanuts on lipids, lipoproteins, and various CHD risk factors, including oxidation, inflammation, and vascular reactivity. Evidence from these studies consistently shows a beneficial effect on these CHD risk factors. The LDL cholesterol-lowering response of nut and peanut studies is greater than expected on the basis of blood cholesterol-lowering equations that are derived from changes in the fatty acid profile of the diet. Thus, in addition to a favorable fatty acid profile, nuts and peanuts contain other bioactive compounds that explain their multiple cardiovascular benefits. Other macronutrients include plant protein and fiber; micronutrients including potassium, calcium, magnesium, and tocopherols; and phytochemicals such as phytosterols, phenolic compounds, resveratrol, and arginine. Nuts and peanuts are food sources that are a composite of numerous cardioprotective nutrients and if routinely incorporated in a healthy diet, population risk of CHD would therefore be expected to decrease markedly.

Maternal Plasma 25-Hydroxyvitamin D Concentrations and the Risk for Gestational Diabetes Mellitus

Abstract: Background: Evidence is accumulating for a role of vitamin D in maintaining normal glucose homeostasis. However, studies that prospectively examined circulating concentrations of 25-hydroxyvitamin D (25-[OH] D) in relation to diabetes risk are limited. Our objective is to determine the association between maternal plasma 25-[OH] D concentrations in early pregnancy and the risk for gestational diabetes mellitus (GDM). Methods: A nested case-control study was conducted among a prospective cohort of 953 pregnant women. Among them, 57 incident GDM cases were ascertained and 114 women who were not diagnosed with GDM were selected as controls. Controls were frequency matched to cases for the estimated season of conception of the index pregnancy. Results: Among women who developed GDM, maternal plasma 25-[OH] D concentrations at an average of 16 weeks of gestation were significantly lower than controls (24.2 vs. 30.1 ng/ml, P,0.001). This difference remained significant (3.62 ng/ml lower on average in GDM cases than controls (P value=0.018)) after the adjustment for maternal age, race, family history of diabetes, and pre-pregnancy BMI. Approximately 33% of GDM cases, compared with 14% of controls (P,0.001), had maternal plasma 25-[OH] D concentrations consistent with a pre-specified diagnosis of vitamin D deficiency (,20 ng/ml). After adjustment for the aforementioned covariates including BMI, vitamin D deficiency was associated with a 2.66-fold (OR (95% CI): 2.66 (1.01–7.02)) increased GDM risk. Moreover, each 5 ng/ml decrease in 25-[OH] D concentrations was related to a 1.29-fold increase in GDM risk (OR (95% CI): 1.29 (1.05–1.60)). Additional adjustment for season and physical activity did not change findings substantially. Conclusions: Findings from the present study suggest that maternal vitamin D deficiency in early pregnancy is significantly associated with an elevated risk for GDM.

Sugar-sweetened beverages and incidence of type 2 diabetes mellitus in African American women.

Abstract: Results: The incidence of type 2 diabetes mellitus was higher with higher intake of both sugar-sweetened soft drinks and fruit drinks. After adjustment for confounding variables including other dietary factors, the incidencerateratiofor2ormoresoftdrinksperdaywas1.24 (95% confidence interval, 1.06-1.45). For fruit drinks, the comparable incidence rate ratio was 1.31 (95% confidence interval, 1.13-1.52). The association of diabetes with soft drink consumption was almost entirely mediated by body mass index, whereas the association with fruit drink consumption was independent of body mass index. Conclusions: Regular consumption of sugar-sweetened soft drinks and fruit drinks is associated with an increasedriskoftype2diabetesmellitusinAfricanAmericanwomen.Whiletherehasbeenincreasingpublicawareness of the adverse health effects of soft drinks, little attention has been given to fruit drinks, which are often marketed as a healthier alternative to soft drinks.

Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population

Abstract: OBJECTIVE—Genome-wide association studies have identified common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX/IDE, EXT2, and LOC387761 loci that significantly increase the risk of type 2 diabetes. We aimed to replicate these observations in a population-based cohort of Chinese Hans and examine the associations of these variants with type 2 diabetes and diabetes-related phenotypes. RESEARCH DESIGN AND METHODS—We genotyped 17 single nucleotide polymorhisms (SNPs) in 3,210 unrelated Chinese Hans, including 424 participants with type 2 diabetes, 878 with impaired fasting glucose (IFG), and 1,908 with normal fasting glucose. RESULTS—We confirmed the associations between type 2 diabetes and variants near CDKAL1 (odds ratio 1.49 [95% CI 1.27‐1.75]; P 8.91 10 7 ) and CDKN2A/B (1.31 [1.12‐1.54]; P 1.0 10 3 ). We observed significant association of SNPs in IGF2BP2 (1.17 [1.03‐1.32]; P 0.014) and SLC30A8 (1.12 [1.01‐1.25]; P 0.033) with combined IFG/type 2 diabetes. The SNPs in CDKAL1, IGF2BP2, and SLC30A8 were also associated with impaired -cell function estimated by homeostasis model assessment of -cell function. When combined, each additional risk allele from CDKAL1-rs9465871, CDKN2A/B-rs10811661, IGF2BP2-rs4402960, and SLC30A8-rs13266634 increased the risk

Variants in the Fat Mass–and Obesity-Associated (FTO) Gene Are Not Associated With Obesity in a Chinese Han Population

Abstract: OBJECTIVE— Recently, genome-wide association studies have provided evidence that several common variants within the fat mass–and obesity-associated ( FTO ) gene were significantly associated with obesity in populations of European origin. However, their effects in other ethnic populations remain to be elucidated. RESEARCH DESIGN AND METHODS— In this study, we examined the association between three FTO variants (rs8050136, rs9939609, and rs9930506) and obesity and related traits in a population-based study of 3,210 unrelated Chinese Han subjects from Shanghai and Beijing. In secondary analyses, we also tested for association with type 2 diabetes and related traits. Logistics regression and generalized linear models were used to test for additive and dominant effects of the risk alleles. RESULTS— The minor allele frequencies of rs8050136, rs9939609, and rs9930506 in our population (0.12, 0.12, and 0.20, respectively) were substantially lower than those observed for populations of European descent (e.g., for CEU population of HapMap: 0.45, 0.48, and 0.45, respectively). Despite our study being sufficiently powered to detect effects similar to those previously reported, none of the FTO SNPs were found to be associated with obesity, overweight, BMI, waist circumference, or body fat percentage. In addition, none of the SNPs exhibited significant associations with fasting levels of plasma glucose, A1C, insulin, or β-cell function (estimated via homeostasis model assessment) under either an additive or a dominant model in the quantitative trait analyses. Analyses stratified by sex or geographical region did not change these observations. CONCLUSIONS— Our data do not support that the FTO common variants are major contributors of obesity or type 2 diabetes in the Chinese Han population.

Association of Dietary Patterns With Cancer Recurrence and Survival in Patients With Stage III Colon Cancer

Abstract: While dietary factors have been implicated in the risk of developing colon cancer, it is not clear whether diet influences the outcome in patients who have established disease This question was addressed in a prospective observational study of 1009 patients with stage III colon cancer who enrolled in a randomized trial of adjuvant chemotherapy in 1999-2001 Participants were asked to complete a semiquantitative food frequency questionnaire midway in the course of chemotherapy and again about 6 months after adjuvant therapy ceased Two major dietary patterns emerged: a prudent pattern with high intakes of fruits and vegetables, poultry, and fish; and a Western pattern with high intakes of meat, fat, refined grains, and deserts The median follow-up interval was 53 years Recurrent disease developed during follow-up in 324 patients, and 223 of them died with recurrent disease Another 28 patients died without documented recurrent disease Higher intake of a Western dietary pattern following diagnosis of colon cancer was associated with significantly worse disease-free survival Compared with patients in the lowest quintile of the Western pattern, those in the highest quintile had an adjusted hazard ratio (AHR) for disease-free survival of 325 (95% confidence interval [CI], 204-519) The AHR for recurrence-free survival was 285 (95% CI, 175-463) For overall survival, the AHR associated with intake of a Western dietary pattern was 232, with a 95% CI of 136-396 The reduced disease-free survival associated with a Western diet was not significantly altered when adjusted for gender, age, lymph node stage, body mass index, level of physical activity, performance status at baseline, or treatment group The prudent dietary pattern, in contrast, was not significantly associated with recurrent cancer or cancer mortality The AHR for disease-free survival, comparing the highest and lowest quintiles of the prudent dietary pattern, was 120 (95% CI, 083-175) There also was no relationship between the prudent pattern and either recurrence-free survival or overall survival The investigators believe this to be the first study in a potentially cured group of colon cancer survivors to analyze the effects of diet Further studies hopefully will identify those elements of a Western dietary pattern that are most closely associated with an adverse outcome

Total and High-Molecular-Weight Adiponectin and Resistin in Relation to the Risk for Type 2 Diabetes in Women

Abstract: Participants: 1038 initially healthy women of the Nurses’ Health Study who developed type 2 diabetes after blood sampling (1989 to 1990) through 2002 and 1136 matched control participants. Measurements: Plasma concentrations of total and high-molecularweight adiponectin and resistin. Results: In multivariate models including body mass index, higher total and high-molecular-weight adiponectin levels were associated with a substantially lower risk for type 2 diabetes (odds ratio [OR] comparing the highest with the lowest quintiles, 0.17 [95% CI, 0.12 to 0.25] for total adiponectin and 0.10 [CI, 0.06 to 0.15] for high-molecular-weight adiponectin). A higher ratio of high-molecular-weight to total adiponectin was associated with a statistically significantly lower risk even after adjustment for total adiponectin (OR, 0.45 [CI, 0.31 to 0.65]). In the multivariate model without body mass index, higher resistin levels were associated with a higher risk for diabetes (OR, 1.68 [CI, 1.25 to 2.25]), but the association was no longer statistically significant after adjustment for body mass index (OR, 1.28 [CI, 0.93 to 1.76]). Limitation: The findings apply mainly to white women and could be partly explained by residual confounding from imperfectly measured or unmeasured variables. Conclusion: Adiponectin is strongly and inversely associated with risk for diabetes, independent of body mass index, whereas resistin is not. The ratio of high-molecular-weight to total adiponectin is related to risk for diabetes independent of total adiponectin, suggesting an important role of the relative proportion of high-molecular-weight adiponectin in diabetes pathogenesis.

The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes risk in women

Abstract: Melanocortin-4 receptor (MC4R) plays critical roles in regulating food intake and energy balance. Recent genome wide scans found common variants near MC4R were related to obesity and insulin resistance. We examined the associations of the reported variants rs17782313 (T>C) and rs17700633 (G>A) with dietary intakes, weight change and diabetes risk in 5724 women (1533 with type 2 diabetes) from a prospective cohort. Under an additive inheritance model, SNP rs17782313 was significantly associated with high intakes of total energy (P = 0.028), total fat (P = 0.008) and protein (P = 0.003). Adjustment for age, BMI, diabetes status and other covariates did not appreciably change the associations. The SNP was also associated with significantly increasing trend of percentage of energy from total fat (P for trend = 0.037). The associations between SNP rs17782313 and higher BMI (P = 0.002) were independent of dietary intakes. In addition, carriers of allele-C had 0.2 kg/m2 greater 10-year increase in BMI from cohort baseline 1976 to 1986 (P = 0.028) compared with the non-carriers. Moreover, per allele-C of rs17782313 was associated with 14% (2–32%) increased risk of type 2 diabetes, adjusting for BMI and other covariates. SNP rs1770833 was not significantly associated with either dietary intakes or obesity traits. In conclusion, the common SNP rs17782313 near MC4R gene was significantly associated with higher intakes of total energy and dietary fat. In addition, the SNP was related to greater long-term weight change and increased risk of diabetes in women.

Prospective study of dietary pattern and risk of Parkinson

Abstract: Background—Several studies have shown associations between Parkinson Disease (PD) risk and individual foods and nutrients with inconsistent results. Objective—We examined associations between dietary patterns and risk of PD in the Health Professionals Follow-Up Study (1986–2002) and the Nurses’ Health Study (1984–2000). Design—We included 49 692 men and 81 676 women free of PD at baseline and used principal components analysis to identify major dietary patterns and the Alternate Healthy Eating Index (AHEI) and the alternate Mediterranean Diet Score (aMed) to assess diet quality. Relative risks (RRs) were computed by using Cox proportional hazards models within each cohort and were pooled by using a random-effects model. Results—We documented 508 new PD cases after 16 y of follow-up. The principal components analysis identified 2 dietary patterns: prudent and Western. The prudent dietary pattern, characterized by high intakes of fruit, vegetables, and fish, was inversely associated with PD risk, but the Western pattern was not. The pooled multivariate-adjusted RR for the top compared with the bottom quintiles of the prudent score was 0.78 (95% CI: 0.56, 1.07; P for trend = 0.04). For the AHEI, the pooled multivariate-adjusted RR for the top compared with the bottom quintile was 0.70 (95% CI: 0.51, 0.94; P for trend = 0.01) and for aMED was 0.75 (95% CI: 0.57, 1.00; P for trend = 0.07). Conclusions—Dietary patterns with a high intake of fruit, vegetables, legumes, whole grains, nuts, fish, and poultry and a low intake of saturated fat and a moderate intake of alcohol may protect against PD. Benefits of a plant-based dietary pattern including fish to PD merit further investigation.

Ferritin concentrations, metabolic syndrome, and type 2 diabetes in middle-aged and elderly chinese.

Abstract: Context: Elevated ferritin concentrations frequently cluster with well-established risk factors of diabetes including obesity, metabolic syndrome, chronic inflammation, and altered circulating adipokines. Few studies, however, have systematically evaluated the effect of these risk factors on ferritin-diabetes association, particularly in Chinese populations. Objective: We aimed to investigate, in a middle-aged and elderly Chinese population, whether elevated ferritin concentrations are associated with higher risk of metabolic syndrome and type 2 diabetes and to what extent the associations were influenced by obesity, inflammation, and adipokines. Design and Methods: We conducted a population-based, cross-sectional survey of 3289 participants aged 50–70 yr in Beijing and Shanghai in 2005. Fasting plasma ferritin, glucose, insulin, lipid profile, glycohemoglobin, inflammatory markers, adipokines, and dietary profile were measured. Results: Median ferritin concentrations were 155.7 ng/ml for men and 111.9 ng...

The Relationship of Coffee Consumption with Mortality

Abstract: Studies have examined the association between coffee consumption and a variety of specific diseases, but the relationship between coffee consumption and all-cause mortality remains unclear. This st...

Plasma uric acid and the risk of type 2 diabetes in a Chinese community.

Abstract: Background: Previous cross-sectional studies have shown hyperuricemia to be prevalent among individuals with metabolic syndrome, but the evidence from prospective studies of an association between uric acid and diabetes risk is limited. We prospectively investigated the association between plasma concentrations of uric acid and the incidence of type 2 diabetes in Chinese individuals. Methods: We conducted a community-based prospective cohort study of 2690 participants (age range, 35–97 years) in the Chin-Shan Community Cardiovascular Cohort Study, who were found to be free of diabetes and cardiovascular disease during baseline assessment at study entry in 1990. During a median 9.0-year follow-up, 548 participants developed type 2 diabetes. Results: High plasma uric acid concentrations were associated with a higher prevalence of metabolic syndrome. After adjustment for age, sex, body mass index, and other covariates, the relative risks (RR) of diabetes according to uric acid quintile were 1.11, 1.29, 1.40, and 1.63 [95% confidence interval (CI), 1.20–2.23; P for trend <0.001]. After additional adjustment for metabolic syndrome, the RR for comparing the participants in the fifth and first uric acid quintiles was 1.40 (95% CI, 1.02–1.92; P for trend = 0.027). In joint analyses, participants who were in the highest uric acid quintile and also had metabolic syndrome had a 3.3-fold greater risk of diabetes (95% CI, 2.27–4.94) than those in the lowest uric acid quintile and without metabolic syndrome. Conclusions: These findings suggest a modest positive association between plasma uric acid concentration and the incidence of type 2 diabetes in Chinese individuals. The association between hyperuricemia and diabetes was partly mediated through the metabolic syndrome.

Coffee Consumption Is Associated With Higher Plasma Adiponectin Concentrations in Women With or Without Type 2 Diabetes A prospective cohort study

Abstract: To test whether the beneficial effects of coffee consumption in metabolism might be explained by changes in circulating levels of adiponectin, we evaluated self-reported habitual coffee and tea consumption and caffeine intake as predictors of plasma adiponectin concentrations among 982 diabetic and 1,058 nondiabetic women without cardiovascular disease from the Nurses' Health Study. Women with and without diabetes who drank >or=4 cups of coffee per day had significantly higher adiponectin concentrations than those who didn't drink coffee regularly (7.7 vs. 6.1 microg/ml, respectively, in diabetic women, P = 0.004; 15.0 vs. 13.2 microg/ml in nondiabetic women, P = 0.04). Similar associations were observed for caffeine intake. We confirm previously reported inverse associations of coffee consumption with inflammatory markers, C-reactive protein, and tumor necrosis factor-alpha receptor II. Adjustment for adiponectin did not weaken these associations, and adjustment for inflammatory markers did not attenuate the association between coffee consumption and adiponectin concentrations. High consumption of caffeine-containing coffee is associated with higher adiponectin and lower inflammatory marker concentrations.

Fat Mass–and Obesity-Associated (FTO) Gene Variant Is Associated With Obesity: Longitudinal Analyses in Two Cohort Studies and Functional Test

Abstract: Objective: To examine the longitudinal association of FTO variant with obesity, circulating adipokine levels, and FTO expression in various materials from human and mouse. Research Design and Methods: We genotyped rs9939609 in 2,287 men and 3,520 women from two prospective cohorts. Plasma adiponectin and leptin were measured in a subset of diabetic men (n=854) and women (n=987). Expression of FTO was tested in adipocytes from db/db mice and mouse macrophages. Results: We observed a trend toward decreasing associations between rs9939609 and BMI at older age (≥65 y) in men, whereas the associations were constant across different age groups in women. In addition, SNP rs9939609 was associated with lower plasma adiponectin [log(e)- means: 1.82±0.04, 1.73±0.03, and 1.68±0.05 for TT, TA, and AA genotypes; P for trend=0.02] and leptin (log(e)- means: 3.56±0.04, 3.63±0.04, and 3.70±0.06; P for trend=0.06] in diabetic women. Adjustment for BMI attenuated the associations. FTO gene was universally expressed in human and mice tissues, including adipocytes. In an ancillary study of adipocytes from db/db mice, FTO expression was ∼50% lower than those from wild-type mice. Conclusions: The association between FTO SNP rs9939609 and obesity risk may decline at older age. The variant affects circulating adiponectin and leptin levels through the changes in BMI. In addition, the expression of FTO gene was reduced in adipocytes from db/db mice.

Genes, environment, and interactions in prevention of type 2 diabetes: a focus on physical activity and lifestyle changes.

Abstract: Type 2 diabetes is one of the fastest growing public health problems worldwide. Both environmental (e.g. physical activity, obesity, and diet) and genetic factors are involved in the development of type 2 diabetes. The associations between physical activity and diabetes risk have been assessed by a number of prospective studies and clinical trials. The results from these studies consistently indicate that the regular physical activity during occupation, commuting, leisure time or daily life reduces the risk of type 2 diabetes by 15-60%; and lifestyle intervention, including counselling for physical activity, nutrition, and body weight, can reduce the risk of type 2 diabetes by 40-60% among adults with impaired glucose tolerance and by about 20% among general individuals. In the past decade, studies using traditional linkage analysis and candidate-gene association approach have found dozens of genes harboring common variants that were related to the common-form type 2 diabetes. However, most reported associations are lack of reproducibility, except TCF7L2, PPARG, CAPN10, and KCNJ11. Since 2007, seven genome-wide association (GWA) studies emerged to generate a list of new diabetes genes. The genetic effects are largely of moderate size. These findings provide novel insight into the diabetes etiology and pave new avenue for predicting the disease risk using genetic information. In addition, data especially those from intervention trials display preliminary but promising evidence that the genetic variants might interact with physical activity in predisposing to type 2 diabetes. The gene-environment interactions merit extensive exploration in large, prospective studies.

Interaction Between Poor Glycemic Control and 9p21 Locus on Risk of Coronary Artery Disease in Type 2 Diabetes

Abstract: Context A common allele on chromosome 9p21 has been repeatedly associated with increased risk of coronary artery disease (CAD) in the general population. However, the magnitude of this effect in the population with diabetes has not been well characterized. Objective To examine the association of the 9p21 variant with CAD in individuals with type 2 diabetes and evaluate its interaction with poor glycemic control. Design, Setting, and Participants (1) Case-control study of 734 type 2 diabetes patients (322 with angiographically diagnosed CAD and 412 with no evidence of CAD) who were recruited between 2001 and 2006 at the Joslin Clinic, Beth Israel Deaconess Medical Center; and (2) independent cohort study of 475 type 2 diabetes patients from the Joslin Clinic whose survival status was monitored from their recruitment between 1993 and 1996 until December 31, 2004. Participants for both studies were genotyped for a representative single-nucleotide polymorphism at 9p21 (rs2383206) and characterized for their long-term glycemic control by averaging multiple hemoglobin A 1c (HbA 1c ) measurements taken in the years before study entry. Main Outcome Measures For the case-control study, association between single-nucleotide polymorphism rs2383206 and CAD defined as angiographically documented stenosis greater than 50% in a major coronary artery or a main branch thereof was assessed and for the cohort study, cumulative 10-year mortality was documented. Results Individuals who were homozygous for the risk allele were significantly more frequent among case than control participants (42.3% vs 28.9P = .0002). This association was unaffected by adjustment for cardiovascular risk factors, but the effect of the risk genotype was significantly magnified (adjusted P for interaction = .048) in the presence of poor glycemic control (worst tertile of the distribution of HbA 1c at examination). Relative to the CAD risk for patients with neither a 9p21 risk allele nor poor glycemic control, the CAD odds for participants having 2 risk alleles but not poor glycemic control were increased 2-fold (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.17-3.41), whereas the odds for study participants with the same genotype and with poor glycemic control were increased 4-fold (OR, 4.27; 95% CI, 2.26-8.01). The interaction was stronger (adjusted P = .005) when a measure of long-term glycemic control (7-year average rather than most recent HbA 1c ) was used with ORs of 7.83 (95% CI, 3.49-17.6) for participants having 2 risk alleles and a history of poor glycemia and 1.54 (95% CI, 0.72-3.30) for participants with the same genotype but without this exposure. A similar interaction between 9p21 variant and poor glycemic control was observed with respect to cumulative 10-year mortality in the cohort study (43.6% in patients with 2 risk alleles and poor glycemic control, 23.1% in individuals with only the 2 risk alleles, 30.0% in individuals with only poor glycemic control, and 31.6% in individuals with neither factor, P for interaction, = .036). Conclusion In this study population, the CAD risk associated with the 9p21 variant was increased in the presence of poor glycemic control in type 2 diabetes.

Passive Smoking and Risk of Peripheral Arterial Disease and Ischemic Stroke in Chinese Women Who Never Smoked

Abstract: Background— The association between secondhand smoke (SHS) and risk of peripheral arterial disease (PAD) and stroke remains uncertain. Methods and Results— We examined the relationship between SHS and cardiovascular diseases, particularly PAD and stroke, in Chinese women who never smoked from a population-based cross-sectional study in Beijing, China. SHS exposure was defined as exposure to another person’s tobacco smoke at home or in the workplace. Cardiovascular disease events included coronary heart disease, stroke, and PAD. PAD was defined by signs of intermittent claudication as measured by the World Health Organization Rose questionnaire and an ankle-brachial index of <0.90. Among 1209 women who never smoked, 39.5% were exposed to SHS at home or in workplaces. Those individuals who were exposed to SHS had a significantly higher risk of coronary heart disease (adjusted odds ratio [OR], 1.69; 95% CI, 1.31 to 2.18) and ischemic stroke (OR, 1.56; 95% CI, 1.03 to 2.35) than those never exposed to SHS aft...