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.

VEGF Receptor-2 Variants Are Associated With Susceptibility to Stroke and Recurrence

Abstract: Background and Purpose—Dysregulation of vessel wall formation, growth, and maintenance may confer susceptibility of stroke. Methods—We tested the hypothesis that variants in 2 genes encoding vascular endothelial growth factor and vascular endothelial growth factor receptor-2 are associated with susceptibility to stroke and its recurrence in a Chinese case–control study comprising 1849 patients with stroke and 1798 control subjects and replicated the investigation in an independent study comprising 327 cases and 327 control subjects. The correlation of variants with carotid artery intima media thickness was examined in 1123 healthy individuals. Results—Compared with their corresponding wild-type genotypes, one coding variant, rs2305948 (Val297Ile), in the vascular endothelial growth factor receptor-2 gene was associated with increased susceptibility to intracerebral hemorrhage (additive model: OR, 2.06; 95% CI, 1.64 to 2.59; P=7.6×10−10; dominant model: OR, 2.20; 95% CI, 1.70 to 2.84; P=1.5×10−9), a promot...

Type of Menopause, Age at Menopause, and Risk of Developing Obstructive Sleep Apnea in Postmenopausal Women.

Abstract: Despite established sex differences and longstanding hypotheses of sex hormone influence in the etiology of obstructive sleep apnea (OSA), we have found no studies that evaluated type of menopause and age at menopause, which affect postmenopausal hormonal milieu, in relation to OSA risk in women. We followed 50,473 postmenopausal women from the Nurses' Health Study during 2002-2012 and 53,827 postmenopausal women from the Nurses' Health Study II during 1995-2013, with 1,712 and 2,560 incident OSA diagnoses, respectively. Compared with natural menopause, the pooled hazard ratio for OSA was 1.27 (95% confidence interval (CI): 1.17, 1.38) for surgical menopause by hysterectomy/oophorectomy. The association remained the same after further accounting for age at menopause (hazard ratio = 1.26, 95% CI: 1.15, 1.38). The risk associated with surgical menopause was higher among women who were not obese as well as among women who never used hormone therapy (P for interaction < 0.05). Earlier menopause was associated with higher OSA risk prior to adjustment for type of menopause (comparing those aged <40 years versus those aged 50-54 years, hazard ratio = 1.21, 95% CI: 1.08, 1.35; P for trend = 0.008), although no association was observed after the adjustment. Surgical as compared with natural menopause was independently associated with higher OSA risk in postmenopausal women. Our results provide additional evidence for a role for sex hormones, particularly abrupt hormonal changes, in modulating OSA risk.

Urinary Excretion of Select Dietary Polyphenol Metabolites Is Associated with a Lower Risk of Type 2 Diabetes in Proximate but Not Remote Follow-Up in a Prospective Investigation in 2 Cohorts of US Women

Abstract: Background: Polyphenols are phytochemicals that possess antioxidant and anti-inflammatory properties and improve glucose metabolism in animal experiments, although data from prospective epidemiologic studies examining polyphenol intakes in relation to type 2 diabetes (T2D) risk are inconsistent. Objectives: We examined urinary excretion of select flavonoid and phenolic acid metabolites, as biomarkers of intake, in relation to T2D risk. Methods: Eight polyphenol metabolites (naringenin, hesperetin, quercetin, isorhamnetin, catechin, epicatechin, caffeic acid, and ferulic acid) were quantified in spot urine samples by liquid chromatography/mass spectrometry among 1111 T2D case-control pairs selected from the Nurses’ Health Study (NHS) and NHSII. Results: Higher urinary excretion of hesperetin was associated with a lower T2D risk after multivariate adjustment: the OR comparing top vs. bottom quartiles was 0.68 (95% CI: 0.49, 0.96), although a linear trend was lacking (P = 0.30). The other measured polyphenols were not significantly associated with T2D risk after multivariate adjustment. However, during the early follow-up period [≤4.6 y (median) since urine sample collection], markers of flavanone intakes (naringenin and hesperetin) and flavonol intakes (quercetin and isorhamnetin) were significantly associated with a lower T2D risk. The ORs (95% CIs) comparing extreme quartiles were 0.61 (0.39, 0.98; P-trend: 0.03) for total flavanones and 0.55 (0.33, 0.92; P-trend: 0.04) for total flavonols (P-interaction with follow-up length: ≤0.04). An inverse association was also observed for caffeic acid during early follow-up only: the OR was 0.52 (95% CI: 0.32, 0.84; P-trend: 0.03). None of these markers was associated with T2D risk during later follow-up. Metabolites of flavan-3-ols and ferulic acid were not associated with T2D risk in either period. Conclusions: These results suggest that specific flavonoid subclasses, including flavanones and flavonols, as well as caffeic acid, are associated with a lower T2D risk in relatively short-term follow-up but not during longer follow-up. Substantial within-person variability of the metabolites in single spot urine samples may limit the ability to capture associations with long-term disease risk.

Interleukin-6 receptor gene, plasma C-reactive protein, and diabetes risk in women.

Abstract: OBJECTIVE— Recent genome-wide association studies (GWASs) related common variants in the interleukin-6 (Il-6) receptor ( IL6R ) gene to plasma C-reactive protein (CRP) concentrations. Because IL6R variants were previously associated with IL-6 levels, we tested whether the associations with CRP were independent of IL-6 and the interactions between IL6R variants and CRP in relation to diabetes risk. RESEARCH DESIGN AND METHODS— Plasma CRP and IL-6 levels and 10 IL6R polymorphisms were determined in a nested case-control study of 633 diabetic and 692 healthy Caucasian women. RESULTS— In both nondiabetic and diabetic women, IL6R polymorphisms were associated with plasma CRP levels, independent of IL-6 concentration. After adjustment of IL-6 levels, CRP concentrations in the genotype AA, AC, and CC of the GWAS polymorphism rs8192284 were 0.32, 0.26, and 0.24 pg/ml, respectively, among nondiabetic women ( P for trend = 0.003; false discovery rate [FDR] = 0.01) and 0.63, 0.48, and 0.43 pg/ml among diabetic women ( P for trend P = 0.0002). In an exploratory analysis, rs8192284 showed significant interactions with CRP levels in relation to diabetes risk ( P for interaction = 0.026). The odds ratios across increasing quartiles of CRP were 2.19 (95% CI 1.42–3.36), 2.03 (1.27–3.23), and 2.92 (1.77–4.82) in the carriers of allele-C and 2.21 (1.18–4.12), 3.77 (1.87–7.57), and 5.02 (2.4–10.5) in the noncarriers. CONCLUSIONS— IL6R variants were significantly associated with plasma CRP, independent of IL-6 levels. IL6R variants may interact with CRP in predicting diabetes risk.

Long-term intake of animal flesh and risk of developing hypertension in three prospective cohort studies

Abstract: Objective:Prospective data are scarce on the relation of red meat, seafood, and poultry consumption with hypertension risk. Although red and processed meats are generally considered to have adverse cardiovascular consequences, seafood is believed to be protective and poultry's effect is controversia

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 …