Showing papers by "Frank B. Hu published in 2009"

Diabetes in Asia: epidemiology, risk factors, and pathophysiology.

Abstract: Context With increasing globalization and East-West exchanges, the increasing epidemic of type 2 diabetes in Asia has far-reaching public health and socioeconomic implications. Objective To review recent data in epidemiologic trends, risk factors, and complications of type 2 diabetes in Asia. Evidence Acquisition Search of MEDLINE using the term diabetes and other relevant keywords to identify meta-analyses, systematic reviews, large surveys, and cohort studies. Separate searches were performed for specific Asian countries. The review was limited to English-language articles published between January 1980 and March 2009; publications on type 1 diabetes were excluded. Evidence Synthesis The prevalence of diabetes in Asian populations has increased rapidly in recent decades. In 2007, more than 110 million individuals in Asia were living with diabetes, with a disproportionate burden among the young and middle aged. Similarly, rates of overweight and obesity are increasing sharply, driven by economic development, nutrition transition, and increasingly sedentary lifestyles. The “metabolically obese” phenotype (ie, normal body weight with increased abdominal adiposity) is common in Asian populations. The increased risk of gestational diabetes, combined with exposure to poor nutrition in utero and overnutrition in later life in some populations, may contribute to the increasing diabetes epidemic through “diabetes begetting diabetes” in Asia. While young age of onset and long disease duration place Asian patients with diabetes at high risk for cardiorenal complications, cancer is emerging as an important cause of morbidity and mortality. Conclusions Type 2 diabetes is an increasing epidemic in Asia, characterized by rapid rates of increase over short periods and onset at a relatively young age and low body mass index. Prevention and control of diabetes should be a top public health priority in Asian populations.

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Abstract: Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Mediterranean Diet and Incidence of and Mortality From Coronary Heart Disease and Stroke in Women

Abstract: Background— Several studies have documented an inverse association between adherence to the Mediterranean diet and risk of coronary heart disease (CHD), but few data are available on the relationsh...

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution

Abstract: To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

Abstract: Vandervell Foundation and Wellcome Trust (068545/Z/02, GR072960, GR076113, GR069224, 086596/Z/08/Z)

Sweetened beverage consumption and risk of coronary heart disease in women 1-4

Abstract: Background: Previous studies have linked full-calorie sugarsweetened beverages (SSBs) with greater weight gain and an increased risk of type 2 diabetes. Objective: We prospectively examined the association between consumption of SSBs and the risk of coronary heart disease (CHD) in women. Design: Women (n ¼ 88,520) from the Nurses’ Health Study aged 34–59 y, without previously diagnosed coronary heart disease (CHD), stroke, or diabetes in 1980, were followed from 1980 to 2004. Consumption of SSBs was derived from 7 repeated foodfrequency questionnaires administered between 1980 and 2002. Relative risks (RRs) for CHD were calculated by using Cox proportional hazards models and adjusted for known cardiovascular disease risk factors. Results: During 24 y of follow-up, we ascertained 3105 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). After standard and dietary risk factors were adjusted for, the RRs (and 95% CIs) of CHD according to categories of cumulative average of SSB consumption (,1/mo, 1–4/mo, 2–6/wk, 1/d, and � 2 servings/ d) were 1.0, 0.96 (0.87, 1.06), 1.04 (0.95, 1.14), 1.23 (1.06, 1.43), and 1.35 (1.07, 1.69) (P for trend , 0.001). Additional adjustment for body mass index, energy intake, and incident diabetes attenuated the associations, but they remained significant. Artificially sweetened beverages were not associated with CHD. Conclusion: Regular consumption of SSBs is associated with a higher risk of CHD in women, even after other unhealthful lifestyle or dietary factors are accounted for. Am J Clin Nutr

Isotemporal Substitution Paradigm for Physical Activity Epidemiology and Weight Change

Abstract: For a fixed amount of time engaged in physical activity, activity choice may affect body weight differently depending partly on other activities' displacement. Typical models used to evaluate effects of physical activity on body weight do not directly address these substitutions. An isotemporal substitution paradigm was developed as a new analytic model to study the time-substitution effects of one activity for another. In 1991-1997, the authors longitudinally examined the associations of discretionary physical activities, with varying activity displacements, with 6-year weight loss maintenance among 4,558 healthy, premenopausal US women who had previously lost >5% of their weight. Results of isotemporal substitution models indicated widely heterogeneous relations with each physical activity type (P < 0.001) depending on the displaced activities. Notably, whereas 30 minutes/day of brisk walking substituted for 30 minutes/day of jogging/running was associated with weight increase (1.57 kg, 95% confidence interval: 0.33, 2.82), brisk walking was associated with lower weight when substituted for slow walking (-1.14 kg, 95% confidence interval: -1.75, -0.53) and with even lower weight when substituted for TV watching. Similar heterogeneous relations with weight change were found for each activity type (TV watching, slow walking, brisk walking, jogging/running) when displaced by other activities across these various models. The isotemporal substitution paradigm may offer new insights for future public health recommendations.

Plasma 25-Hydroxyvitamin D Concentration and Metabolic Syndrome Among Middle-Aged and Elderly Chinese Individuals

Abstract: OBJECTIVE To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome in the Chinese population. RESEARCH DESIGN AND METHODS Plasma 25(OH)D was measured in a cross-sectional sample of 1,443 men and 1,819 women aged 50–70 years from Beijing and Shanghai. Metabolic syndrome was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Fasting plasma glucose, insulin, lipid profile, A1C, and inflammatory markers were measured. RESULTS The geometric mean of plasma 25(OH)D was 40.4 nmol/l, and percentages of vitamin D deficiency [25(OH)D <50 nmol/l] and insufficiency [50 ≤ 25(OH)D <75 nmol/l] were 69.2 and 24.4%, respectively. Compared with the highest 25(OH)D quintile (≥57.7 nmol/l), the odds ratio for metabolic syndrome in the lowest quintile (≤28.7 nmol/l) was 1.52 (95% CI 1.17–1.98, P trend = 0.0002) after multiple adjustment. Significant inverse associations also existed between 25(OH)D and individual metabolic syndrome components plus A1C. Moreover, we observed significant inverse associations of 25(OH)D with fasting insulin and the insulin resistance index (homeostasis model assessment of insulin resistance [HOMA-IR]) in overweight and obese individuals (BMI ≥24 kg/m2) but not in their normal-weight counterparts (test for interaction: P = 0.0363 and 0.0187 for insulin and HOMA-IR, respectively). CONCLUSIONS Vitamin D deficiency is common in the middle-aged and elderly Chinese population, and a low 25(OH)D level is significantly associated with an increased risk of having metabolic syndrome and insulin resistance. Prospective studies and randomized clinical trials are warranted to determine the role of 25(OH)D in the development of metabolic syndrome and related metabolic diseases.

Joint Effects of Common Genetic Variants on the Risk for Type 2 Diabetes in U.S. Men and Women of European Ancestry

Abstract: Type 2 diabetes is a rapidly growing public health issue with a major impact on morbidity and premature mortality worldwide (1). The recent increase in the prevalence of this disease is largely attributable to environmental factors; however, convincing evidence shows that genetic factors also play an important role in causing type 2 diabetes (2, 3). Initial efforts to identify type 2 diabetes susceptibly genes favored genome-wide linkage and candidate gene association studies. These approaches identified common single nucleotide polymorphisms (SNPs) in PPARG, KCNJ11, and TCF7L2, which have been widely replicated in populations of various ethnicity (4 – 6). The advent of genome-wide association studies promises more efficient identification of susceptibility genes. Recent genome-wide association studies have discovered several new potential loci, including HHEX, CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and WFS1 (7–14). Variants in FTO and MC4R were also associated with type 2 diabetes, but the associations were entirely mediated by body mass index (BMI) (15, 16). Given our growing knowledge of the genetic factors that predispose to type 2 diabetes and the decreasing costs of genotyping, genetic screening for persons at high risk for type 2 diabetes has received considerable attention. The risk attributable to an individual variant is modest and unlikely to have important clinical utility. However, a combination of the major genetic factors may contribute substantially to the disease risk and will be useful in characterizing high-risk populations. Although the joint effects of type 2 diabetes loci identified from genome-wide association studies have been investigated previously (17–22), few studies have comprehensively investigated the impact of conventional risk factors, such as BMI, lifestyle, and family history, on these genetic effects. We sought to confirm associations reported by genome-wide association studies and to examine the joint genetic effects of established type 2 diabetes risk variants and their combination with conventional risk factors on type 2 diabetes risk in 2 prospective cohorts: the Health Professionals Follow-up Study (HPFS) and the Nurses’ Health Study (NHS).

Prospective Study of Zinc Intake and Risk of Type 2 Diabetes in Women

Abstract: OBJECTIVE The aim of this study is to investigate the intake of zinc in relation to risk of type 2 diabetes in U.S. women. RESEARCH DESIGN AND METHODS Dietary intakes of zinc and other nutrients were assessed and updated using a validated food frequency questionnaire from 1980 to 2002 among 82,297 women who were aged 33–60 years at baseline in 1980 and followed up to 2004 in the Nurses9 Health Study. RESULTS During the 24 years of follow-up, 6,030 incident cases of type 2 diabetes were ascertained. After adjustment of lifestyle and dietary risk factors, the relative risks (RRs) (95% CI) of type 2 diabetes comparing the highest with the lowest quintiles were 0.90 (0.82–0.99) ( P trend = 0.04) for total zinc intake and 0.92 (0.84–1.00) ( P trend = 0.009) for dietary zinc intake from food sources, respectively. We further found an inverse association for dietary zinc to heme iron ratio. After multivariate adjustment of covariates, the RRs (95% CI) across quintiles of this ratio were 1.0 (reference), 0.93 (0.86–1.01), 0.86 (0.79–0.94), 0.82 (0.75–0.90), and 0.72 (0.66–0.80), respectively ( P trend CONCLUSIONS Higher zinc intake may be associated with a slightly lower risk of type 2 diabetes in women. More studies are warranted to confirm this association and to explore potential mechanisms.

Beyond odds ratios — communicating disease risk based on genetic profiles

Abstract: The success of genome wide association (GWA) studies raises the hope that disease-associated markers will be useful in predicting disease risk. However, the metrics used to report effect sizes in GWA studies are not useful for determining the accuracy of genetic profiles. The brisk discovery of novel inherited disease markers by genome-wide association (GWA) studies has raised expectations for predicting disease risk by analysing multiple common alleles. However, the statistics used during the discovery phase of research (such as odds ratios or p values for association) are not the most appropriate measures for evaluating the predictive value of genetic profiles. We argue that other measures — such as sensitivity, specificity, and positive and negative predictive values — are more useful when proposing a genetic profile for risk prediction.

A prediction model for type 2 diabetes risk among Chinese people.

Abstract: Aims/hypothesis A range of prediction rules for the onset of type 2 diabetes have been proposed. However, most studies have been conducted in white groups and it is not clear whether these models apply to Asian populations. The purpose of this study was to construct a simple points model for predicting incident diabetes among Chinese people.

Coffee Consumption and Risk of Stroke in Women

Abstract: Background— Data on the association between coffee consumption and risk of stroke are sparse. We assessed the association between coffee consumption and the risk of stroke over 24 years of follow-up in women. Methods and Results— We analyzed data from a prospective cohort of 83 076 women in the Nurses’ Health Study without history of stroke, coronary heart disease, diabetes, or cancer at baseline. Coffee consumption was assessed first in 1980 and then repeatedly every 2 to 4 years, with follow-up through 2004. We documented 2280 strokes, of which 426 were hemorrhagic, 1224 were ischemic, and 630 were undetermined. In multivariable Cox regression models with adjustment for age, smoking status, body mass index, physical activity, alcohol intake, menopausal status, hormone replacement therapy, aspirin use, and dietary factors, the relative risks (RRs) of stroke across categories of coffee consumption (<1 cup per month, 1 per month to 4 per week, 5 to 7 per week, 2 to 3 per day, and ≥4 per day) were 1, 0.98 (...

Regular Consumption of Nuts Is Associated with a Lower Risk of Cardiovascular Disease in Women with Type 2 Diabetes

Abstract: Higher nut consumption has been associated with lower risk of coronary heart disease (CHD) events in several epidemiologic studies. The study examined the association between intake of nuts and incident cardiovascular disease (CVD) in a cohort of women with type 2 diabetes. For the primary analysis, there were 6309 women with type 2 diabetes who completed a validated FFQ every 2–4 y between 1980 and 2002 and were without CVD or cancer at study entry. Major CVD events included incident myocardial infarction (MI), revascularization, and stroke. During 54,656 person-years of follow-up, there were 452 CHD events (including MI and revascularization) and 182 incident stroke cases. Frequent nut and peanut butter consumption was inversely associated with total CVD risk in age-adjusted analyses. After adjustment for conventional CVD risk factors, consumption of at least 5 servings/wk of nuts or peanut butter [serving size, 28 g (1 ounce) for nuts and 16 g (1 tablespoon) for peanut butter] was significantly associated with a lower risk of CVD (relative risk = 0.56; 95% CI: 0.36–0.89). Furthermore, when we evaluated plasma lipid and inflammatory biomarkers, we observed that increasing nut consumption was significantly associated with a more favorable plasma lipid profile, including lower LDL cholesterol, non-HDL cholesterol, total cholesterol, and apolipoprotein-B-100 concentrations. However, we did not observe significant associations for HDL cholesterol or inflammatory markers. These data suggest that frequent nut and peanut butter consumption is associated with a significantly lower CVD risk in women with type 2 diabetes.

Associations of physical activity with inflammatory factors, adipocytokines, and metabolic syndrome in middle-aged and older chinese people

Abstract: Background—Inflammatory factors, adipocytokines, and the metabolic syndrome are important determinants of cardiometabolic disease. It remains unclear how physical activity is related to these risk factors. Our objective was to investigate single and joint associations of physical activity with inflammatory factors, adipocytokines, and the metabolic syndrome among middle-aged and older Chinese people. Methods and Results—A total of 3289 individuals (1458 men, 1831 women) 50 to 70 years of age participated in a population-based cross-sectional survey in Beijing and Shanghai, China. Levels of total physical activity were assessed with the International Physical Activity Questionnaire. High-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor- receptor 2, adiponectin, and retinol-binding protein 4 were measured. The metabolic syndrome was defined using the updated National Cholesterol Education Program/Adult Treatment Panel III criteria for Asian Americans. Plasma concentrations of high-sensitivity C-reactive protein were 1.58, 1.74, and 1.27 mg/L (P0.0138) and of adiponectin were 16.12, 16.20, and 17.21 mg/L (P0.0078) among individuals with low, medium, and high levels of total physical activity, respectively, with adjustment for potential confounders. In the multivariable-adjusted logistic regression analyses, participants with higher levels of total physical activity had a lower risk of having the metabolic syndrome (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.85; P for trend0.001) compared with those with lower levels. Conclusions—Being physically active is associated with a better profile of inflammatory factors and adipocytokines and a reduced risk of having the metabolic syndrome among Chinese people. (Circulation. 2009;119:2969-2977.)

Expert panel on weight loss surgery: executive report update.

Abstract: Rapid shifts in the demographics and techniques of weight loss surgery (WLS) have led to new issues, new data, new concerns, and new challenges. In 2004, this journal published comprehensive evidence-based guidelines on WLS. In this issue, we've updated those guidelines to assure patient safety in this fast-changing field. WLS involves a uniquely vulnerable population in need of specialized resources and ongoing multidisciplinary care. Timely best-practice updates are required to identify new risks, develop strategies to address them, and optimize treatment. Findings in these reports are based on a comprehensive review of the most current literature on WLS; they directly link patient safety to methods for setting evidence-based guidelines developed from peer-reviewed scientific publications. Among other outcomes, these reports show that WLS reduces chronic disease risk factors, improves health, and confers a survival benefit on those who undergo it. The literature also shows that laparoscopy has displaced open surgery as the predominant approach; that government agencies and insurers only reimburse procedures performed at accredited WLS centers; that best practice care requires close collaboration between members of a multidisciplinary team; and that new and existing facilities require wide-ranging changes to accommodate growing numbers of severely obese patients. More than 100 specialists from across the state of Massachusetts and across the many disciplines involved in WLS came together to develop these new standards. We expect them to have far-reaching effects of the development of health care policy and the practice of WLS.

A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients.

Abstract: Our pre-clinical studies demonstrated that intratumoral vaccination with a recombinant oncolytic type 2 adenovirus overexpressing the heat shock protein (HSP)70 protein, designated as H103, can inhibit primary and metastatic tumors through enhanced oncolytic activity and HSP-mediated immune responses against shared and mutated tumor antigens. In the pre-clinical studies of local H103 administration, no significant toxicity was observed in the animal trials with mice, cavy or rhesus monkeys. A phase I clinical trial of intratumoral injection of H103 was conducted in the patients with advanced solid tumors. A total of 27 patients were injected intratumorally with H103 in a dose-escalation study from a dose of 2.5 x 10(7) to 3.0 x 10(12) viral particles (VPs). The maximum tolerated dose of H103 was not defined. Two patients developed dose-limiting toxicities of grade III fever at the dose of 1.5 x 10(12) VP and transient grade IV thrombocytopenia at the dose of 3.0 x 10(12) VP. The common adverse events were mainly mild to moderate (grade I/II) in nature, including fever, mild injection-site reaction, leucopenia, lymphopenia, thrombocytopenia and hypochromia. The objective response (complete response+partial response) to H103-injected tumors was 11.1% (3/27), and the clinical benefit rate (complete response+partial response+minor response+stable disease) was 48.1%. Interestingly, transient and partial regression of distant, uninjected tumors was observed in three patients. The numbers of immune cells (CD4(+) and CD8(+) T cells, and natural killer cells) were elevated after H103 administration, but without statistical significance. This phase I trial demonstrates that intratumoral administration of H103 can be safely applied to cancer patients and shows promising clinical antitumor activity, warranting a further clinical investigation.

Prospective study of pre-gravid sugar-sweetened beverage consumption and the risk of gestational diabetes mellitus.

Abstract: OBJECTIVE — Consumption of sugar-sweetened beverages (SSBs) was related to an elevated risk of type 2 diabetes and insulin resistance in several recent studies among middle- or olderaged populations. Studies on SSB consumption and glucose intolerance among pregnant women, however, are lacking. We therefore examined the association between regular SSB consumption before pregnancy and the risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS — This was a prospective study among 13,475 U.S. women who reported at least one singleton pregnancy between 1992 and 2001 in the Nurses’ Health Study II. GDM was self-reported and validated by medical record review in a subsample. Cox proportional hazards models with multivariate adjustments were applied to examine the association of SSB consumption with GDM risk. RESULTS — During 10 years of follow-up, 860 incident GDM case subjects were identified. After adjustment for age, parity, race, physical activity, smoking, alcohol intake, prepregnancy BMI, and Western dietary pattern, intake of sugar-sweetened cola was positively associated with the risk of GDM, whereas no significant association was found for other SSBs and diet beverages. Compared with women who consumed 1 serving/month, those who consumed 5 servings/ week of sugar-sweetened cola had a 22% greater GDM risk (relative risk 1.22 [95% CI 1.01–1.47]). CONCLUSIONS — Findings from this study suggest that prepregnancy higher consumption of sugar-sweetened cola (5 servings/week) is associated with an elevated GDM risk, whereas no significant association with GDM risk was observed for other SSBs and diet beverages. Diabetes Care 32:2236–2241, 2009

Adiposity and weight change in mid-life in relation to healthy survival after age 70 in women: prospective cohort study.

Abstract: Objective: To examine the hypothesis that mid-life adiposity is associated with a reduced probability of maintaining an optimal health status among those who survive to older ages. Design: Prospective cohort study. Setting: The Nurses’ Health Study, United States. Participants: 17 065 women who survived until at least the age of 70, provided information on occurrence of chronic disease, cognitive function, physical function, and mental health at older ages, and were free from major chronic diseases at mid-life (mean age was 50 at baseline in 1976). Main outcome measures: Healthy survival to age 70 and over was defined as having no history of 11 major chronic diseases and having no substantial cognitive, physical, or mental limitations. Results: Of the women who survived until at least age 70, 1686 (9.9%) met our criteria for healthy survival. Increased body mass index (BMI) at baseline was significantly associated with linearly reduced odds of healthy survival compared with usual survival, after adjustment for various lifestyle and dietary variables (P<0.001 for trend). Compared with lean women (BMI 18.5-22.9), obese women (BMI ≥30) had 79% lower odds of healthy survival (odds ratio 0.21, 95% confidence interval 0.15 to 0.29). In addition, the more weight gained from age 18 until mid-life, the less likely was healthy survival after the age of 70. The lowest odds of healthy survival were among women who were overweight (BMI ≥25) at age 18 and gained ≥10 kg weight (0.18, 0.09 to 0.36), relative to women who were lean (BMI 18.5-22.9) and maintained a stable weight. Conclusions: These data provide evidence that adiposity in mid-life is strongly related to a reduced probability of healthy survival among women who live to older ages, and emphasise the importance of maintaining a healthy weight from early adulthood.