Frank B. Hu

Bio: Frank B. Hu is an academic researcher from Harvard University. The author has contributed to research in topics: Type 2 diabetes & Diabetes mellitus. The author has an hindex of 250, co-authored 1675 publications receiving 253464 citations. Previous affiliations of Frank B. Hu include Southwest University & Brigham and Women's Hospital.

Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?

Abstract: The INSIG2 rs7566605 polymorphism was identified for obesity (BMI> or =30 kg/m(2)) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status ('healthy population', HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I(2) measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I(2) measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI> or =32.5, 35.0, 37.5, 40.0 kg/m(2) versus BMI<25 kg/m(2)) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far.

Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study

Abstract: Objective To evaluate the combined associations of diet, physical activity, moderate alcohol consumption, and smoking with body weight on risk of all cause and cause specific mortality. Design Longitudinal study with up to 32 years of follow-up. Setting Nurses’ Health Study (1980-2012) and Health Professionals Follow-up Study (1986-2012). Participants 74 582 women from the Nurses’ Health Study and 39 284 men from the Health Professionals Follow-up Study who were free from cardiovascular disease and cancer at baseline. Main outcome measures Exposures included body mass index (BMI), score on the alternate healthy eating index, level of physical activity, smoking habits, and alcohol drinking while outcome was mortality (all cause, cardiovascular, cancer). Cox proportional hazard models were used to calculate the adjusted hazard ratios of all cause, cancer, and cardiovascular mortality with their 95% confidence intervals across categories of BMI, with 22.5-24.9 as the reference. Results During up to 32 years of follow-up, there were 30 013 deaths (including 10 808 from cancer and 7189 from cardiovascular disease). In each of the four categories of BMI studied (18.5-22.4, 22.5-24.9, 25-29.9, ≥30), people with one or more healthy lifestyle factors had a significantly lower risk of total, cardiovascular, and cancer mortality than individuals with no low risk lifestyle factors. A combination of at least three low risk lifestyle factors and BMI between 18.5-22.4 was associated with the lowest risk of all cause (hazard ratio 0.39, 95% confidence interval 0.35 to 0.43), cancer (0.40, 0.34 to 0.47), and cardiovascular (0.37, 0.29 to 0.46) mortality, compared with those with BMI between 22.5-24.9 and none of the four low risk lifestyle factors. Conclusion Although people with a higher BMI can have lower risk of premature mortality if they also have at least one low risk lifestyle factor, the lowest risk of premature mortality is in people in the 18.5-22.4 BMI range with high score on the alternate healthy eating index, high level of physical activity, moderate alcohol drinking, and who do not smoke. It is important to consider diet and lifestyle factors in the evaluation of the association between BMI and mortality.

Gene-environment interactions in the development of type 2 diabetes: recent progress and continuing challenges.

Abstract: Type 2 diabetes (T2D) is thought to arise from the complex interplay of both genetic and environmental factors. Since the advent of genome-wide association studies (GWAS), we have seen considerable progress in our understanding of the role that genetics and gene-environment interactions play in the development of T2D. Recent work suggests that the adverse effect of several T2D loci may be abolished or at least attenuated by higher physical activity levels or healthy lifestyle, whereas low physical activity and dietary factors characterizing a Western dietary pattern may augment it. However, there still remain inconsistencies warranting further investigation. Lack of statistical power and measurement errors for the environmental factors continue to challenge our efforts for characterizing interactions. Although our recent focus on established T2D loci is reasonable, we may be overlooking many other potential loci not captured by recent T2D GWAS. Agnostic approaches to the discovery of gene and environment ...

Dietary Fat Intake and Cognitive Decline in Women With Type 2 Diabetes

Abstract: OBJECTIVE Individuals with type 2 diabetes have high risk of late-life cognitive impairment, yet little is known about strategies to modify risk. Targeting insulin resistance and vascular complications—both associated with cognitive decline—may be a productive approach. We investigated whether dietary fat, which modulates glucose and lipid metabolism, might influence cognitive decline in older adults with diabetes. RESEARCH DESIGN AND METHODS Beginning in 1995–1999, we evaluated cognitive function in 1,486 Nurses' Health Study participants, aged ≥70 years, with type 2 diabetes; second evaluations were conducted 2 years later. Dietary fat intake was assessed regularly beginning in 1980; we considered average intake from 1980 (at midlife) through initial cognitive interview and also after diabetes diagnosis. We used multivariate-adjusted linear regression models to obtain mean differences in cognitive decline across tertiles of fat intake. RESULTS Higher intakes of saturated and trans fat since midlife, and lower polyunsaturated to saturated fat ratio, were each highly associated with worse cognitive decline in these women. On a global score averaging all six cognitive tests, mean decline among women in the highest trans fat tertile was 0.15 standard units worse than that among women in the lowest tertile (95% CI −0.24 to −0.06, P = 0.002); this mean difference was comparable with the difference we find in women 7 years apart in age. Results were similar when we analyzed diet after diabetes diagnosis. CONCLUSIONS These findings suggest that lower intakes of saturated and trans fat and higher intake of polyunsaturated fat relative to saturated fat may reduce cognitive decline in individuals with type 2 diabetes.

Genome-Wide Association Study Identifies Variants at the IL18 -BCO2 Locus Associated With Interleukin-18 Levels

Abstract: Objective— Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the processes of innate and acquired immunities and associated with cardiovascular disease and type 2 diabetes. We sought to identify the common genetic variants associated with IL-18 levels. Methods and Results— We performed a 2-stage genome-wide association study among women of European ancestry from the Nurses’ Health Study (NHS) and Women’s Genome Health Study (WGHS). IL-18 levels were measured by ELISA. In the discovery stage (NHS, n=1523), 7 single-nucleotide polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 1×10−5 significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31×10−8). In silico replication in WGHS (435 women) confirmed these findings. The combined analysis of the 2 studies indicated that SNPs rs2115763, rs1834481, and rs7106524 reached a genome-wide significance level (P<5×10−8). Forward selection analysis indicated that SNPs rs211...

Vitamin D Deficiency

Abstract: Once foods in the United States were fortified with vitamin D, rickets appeared to have been conquered, and many considered major health problems from vitamin D deficiency resolved. But vitamin D deficiency is common. This review considers the role of vitamin D in skeletal and nonskeletal health and suggests strategies for the prevention and treatment of vitamin D deficiency.

Diagnosis and Management of the Metabolic Syndrome An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

Abstract: The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …