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IMPORTANCE: Changes in the economy, nutrition policies, and food processing methods can affect dietary macronutrient intake and diet quality. It is essential to evaluate trends in dietary intake, food sources, and diet quality to inform policy makers. OBJECTIVE: To investigate trends in dietary macronutrient intake, food sources, and diet quality among US adults. DESIGN, SETTING, AND PARTICIPANTS: Serial cross-sectional analysis of the US nationally representative 24-hour dietary recall data from 9 National Health and Nutrition Examination Survey cycles (1999-2016) among adults aged 20 years or older. EXPOSURE: Survey cycle. MAIN OUTCOMES AND MEASURES: Dietary intake of macronutrients and their subtypes, food sources, and the Healthy Eating Index 2015 (range, 0-100; higher scores indicate better diet quality; a minimal clinically important difference has not been defined). RESULTS: There were 43 996 respondents (weighted mean age, 46.9 years; 51.9% women). From 1999 to 2016, the estimated energy from total carbohydrates declined from 52.5% to 50.5% (difference, −2.02%; 95% CI, −2.41% to −1.63%), whereas that of total protein and total fat increased from 15.5% to 16.4% (difference, 0.82%; 95% CI, 0.67%-0.97%) and from 32.0% to 33.2% (difference, 1.20%; 95% CI, 0.84%-1.55%), respectively (all P

Data describing the effects of weight gain across adulthood on overall health are important for weight control.To examine the association of weight gain from early to middle adulthood with health outcomes later in life.Cohort analysis of US women from the Nurses' Health Study (1976-June 30, 2012) and US men from the Health Professionals Follow-Up Study (1986-January 31, 2012) who recalled weight during early adulthood (at age of 18 years in women; 21 years in men), and reported current weight during middle adulthood (at age of 55 years).Weight change from early to middle adulthood (age of 18 or 21 years to age of 55 years).Beginning at the age of 55 years, participants were followed up to the incident disease outcomes. Cardiovascular disease, cancer, and death were confirmed by medical records or the National Death Index. A composite healthy aging outcome was defined as being free of 11 chronic diseases and major cognitive or physical impairment.A total of 92 837 women (97% white; mean [SD] weight gain: 12.6 kg [12.3 kg] over 37 years) and 25 303 men (97% white; mean [SD] weight gain: 9.7 kg [9.7 kg] over 34 years) were included in the analysis. For type 2 diabetes, the adjusted incidence per 100 000 person-years was 207 among women who gained a moderate amount of weight (≥2.5 kg to10 kg) vs 110 among women who maintained a stable weight (weight loss ≤2.5 kg or gain2.5 kg) (absolute rate difference [ARD] per 100 000 person-years, 98; 95% CI, 72 to 127) and 258 vs 147, respectively, among men (ARD, 111; 95% CI, 58 to 179); hypertension: 3415 vs 2754 among women (ARD, 662; 95% CI, 545 to 782) and 2861 vs 2366 among men (ARD, 495; 95% CI, 281 to 726); cardiovascular disease: 309 vs 248 among women (ARD, 61; 95% CI, 38 to 87) and 383 vs 340 among men (ARD, 43; 95% CI, -14 to 109); obesity-related cancer: 452 vs 415 among women (ARD, 37; 95% CI, 4 to 73) and 208 vs 165 among men (ARD, 42; 95% CI, 0.5 to 94). Among those who gained a moderate amount of weight, 3651 women (24%) and 2405 men (37%) achieved the composite healthy aging outcome. Among those who maintained a stable weight, 1528 women (27%) and 989 men (39%) achieved the composite healthy aging outcome. The multivariable-adjusted odds ratio for the composite healthy aging outcome associated with moderate weight gain was 0.78 (95% CI, 0.72 to 0.84) in women and 0.88 (95% CI, 0.79 to 0.97) in men. Higher amounts of weight gain were associated with greater risks of major chronic diseases and lower likelihood of healthy aging.In these cohorts of health professionals, weight gain during adulthood was associated with significantly increased risk of major chronic diseases and decreased odds of healthy aging. These findings may help counsel patients regarding the risks of weight gain.

Several studies have suggested that depression is associated with an increased risk of stroke; however, the results are inconsistent.To conduct a systematic review and meta-analysis of prospective studies assessing the association between depression and risk of developing stroke in adults.A search of MEDLINE, EMBASE, and PsycINFO databases (to May 2011) was supplemented by manual searches of bibliographies of key retrieved articles and relevant reviews.We included prospective cohort studies that reported risk estimates of stroke morbidity or mortality by baseline or updated depression status assessed by self-reported scales or clinician diagnosis.Two independent reviewers extracted data on depression status at baseline, risk estimates of stroke, study quality, and methods used to assess depression and stroke. Hazard ratios (HRs) were pooled using fixed-effect or random-effects models when appropriate. Associations were tested in subgroups representing different participant and study characteristics. Publication bias was evaluated with funnel plots and Begg test.The search yielded 28 prospective cohort studies (comprising 317,540 participants) that reported 8478 stroke cases (morbidity and mortality) during a follow-up period ranging from 2 to 29 years. The pooled adjusted HRs were 1.45 (95% CI, 1.29-1.63; P for heterogeneity.001; random-effects model) for total stroke, 1.55 (95% CI, 1.25-1.93; P for heterogeneity = .31; fixed-effects model) for fatal stroke (8 studies), and 1.25 (95% CI, 1.11-1.40; P for heterogeneity = .34; fixed-effects model) for ischemic stroke (6 studies). The estimated absolute risk differences associated with depression were 106 cases for total stroke, 53 cases for ischemic stroke, and 22 cases for fatal stroke per 100,000 individuals per year. The increased risk of total stroke associated with depression was consistent across most subgroups.Depression is associated with a significantly increased risk of stroke morbidity and mortality.

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.

Context: Emerging epidemiological evidence suggests that higher coffee consumption may reduce the risk of type 2 diabetes. Objective: To examine the association between habitual coffee consumption and risk of type 2 diabetes and related outcomes. Data Sources and Study Selection: We searched MEDLINE through January 2005 and examined the reference lists of the retrieved articles. Because this review focuses on studies of habitual coffee consumption and risk of type 2 diabetes, we excluded studies of type 1 diabetes, animal studies, and studies of short-term exposure to coffee or caffeine, leaving 15 epidemiological studies (cohort or cross-sectional). Data Extraction: Information on study design, participant characteristics, measurement of coffee consumption and outcomes, adjustment for potential confounders, and estimates of associations was abstracted independently by 2 investigators. Data Synthesis: We identified 9 cohort studies of coffee consumption and risk of type 2 diabetes, including 193 473 participants and 8394 incident cases of type 2 diabetes, and calculated summary relative risks (RRs) using a random-effects model. The RR of type 2 diabetes was 0.65 (95% confidence interval [CI], 0.54-0.78) for the highest (≥6 or ≥7 cups per day) and 0.72 (95% CI, 0.62-0.83) for the second highest (4-6 cups per day) category of coffee consumption compared with the lowest consumption category (0 or ≤2 cups per day). These associations did not differ substantially by sex, obesity, or region (United States and Europe). In the cross-sectional studies conducted in northern Europe, southern Europe, and Japan, higher coffee consumption was consistently associated with a lower prevalence of newly detected hyperglycemia, particularly postprandial hyperglycemia. Conclusions: This systematic review supports the hypothesis that habitual coffee consumption is associated with a substantially lower risk of type 2 diabetes. Longer-term intervention studies of coffee consumption and glucose metabolism are warranted to examine the mechanisms underlying the relationship between coffee consumption and type 2 diabetes. ©2005 American Medical Association. All rights reserved.

Type 2 diabetes is a common manifestation of hemochromatosis, a disease of iron overload. However, it is not clear whether higher iron stores predict the development of type 2 diabetes in a healthy population.To examine plasma ferritin concentration and the ratio of the concentrations of transferrin receptors to ferritin in relation to risk of type 2 diabetes.Prospective nested case-control study within the Nurses' Health Study cohort. Of the 32 826 women who provided blood samples during 1989-1990 and were free of diagnosed diabetes, cardiovascular disease, and cancer, 698 developed diabetes during 10 years of follow-up. The controls (n = 716) were matched to cases on age, race, and fasting status; and on body mass index (BMI) for cases in the top BMI decile.Incident cases of type 2 diabetes.Among cases, the mean (SD) concentration of ferritin was significantly higher (109 [105] vs 71.5 [68.7] ng/mL for controls; P.001 for difference) and the mean (SD) ratio of transferrin receptors to ferritin was significantly lower (102 [205] vs 141 [340], respectively; P =.01). In conditional logistic regression stratified on the matching factors and controlled for BMI and other diabetes risk factors, the multivariate relative risks [RRs] of incident type 2 diabetes across increasing quintiles of ferritin were 1.00, 1.09 (95% confidence interval [CI], 0.70-1.70), 1.26 (95% CI, 0.82-1.95), 1.30 (95% CI, 0.83-2.04), and 2.68 (95% CI, 1.75-4.11) (P.001 for trend). The RRs across increasing quintiles of transferrin receptors to ferritin ratio were 2.44 (95% CI, 1.61-3.71), 1.00 (95% CI, 0.64-1.56), 1.13 (95% CI, 0.73-1.74), 0.99 (95% CI, 0.64-1.53), and 1.00 (P =.01 for trend). Further adjustment for an inflammatory marker (C-reactive protein) did not change the results appreciably. The associations persisted within strata defined by levels of BMI, menopausal status, alcohol consumption, and C-reactive protein.Higher iron stores (reflected by an elevated ferritin concentration and a lower ratio of transferrin receptors to ferritin) are associated with an increased risk of type 2 diabetes in healthy women independent of known diabetes risk factors.

ContextCurrent public health campaigns to reduce obesity and type 2 diabetes have largely focused on increasing exercise, but have paid little attention to the reduction of sedentary behaviors.ObjectiveTo examine the relationship between various sedentary behaviors, especially prolonged television (TV) watching, and risk of obesity and type 2 diabetes in women.Design, Setting, and ParticipantsProspective cohort study conducted from 1992 to 1998 among women from 11 states in the Nurses' Health Study. The obesity analysis included 50 277 women who had a body mass index (BMI) of less than 30 and were free from diagnosed cardiovascular disease, diabetes, or cancer and completed questions on physical activity and sedentary behaviors at baseline. The diabetes analysis included 68 497 women who at baseline were free from diagnosed diabetes mellitus, cardiovascular disease, or cancer.Main Outcome MeasuresOnset of obesity and type 2 diabetes mellitus.ResultsDuring 6 years of follow-up, 3757 (7.5%) of 50 277 women who had a BMI of less than 30 in 1992 became obese (BMI ≥30). Overall, we documented 1515 new cases of type 2 diabetes. Time spent watching TV was positively associated with risk of obesity and type 2 diabetes. In the multivariate analyses adjusting for age, smoking, exercise levels, dietary factors, and other covariates, each 2-h/d increment in TV watching was associated with a 23% (95% confidence interval [CI], 17%-30%) increase in obesity and a 14% (95% CI, 5%-23%) increase in risk of diabetes; each 2-h/d increment in sitting at work was associated with a 5% (95% CI, 0%-10%) increase in obesity and a 7% (95% CI, 0%-16%) increase in diabetes. In contrast, standing or walking around at home (2 h/d) was associated with a 9% (95% CI, 6%-12%) reduction in obesity and a 12% (95% CI, 7%-16%) reduction in diabetes. Each 1 hour per day of brisk walking was associated with a 24% (95% CI, 19%-29%) reduction in obesity and a 34% (95% CI, 27%-41%) reduction in diabetes. We estimated that in our cohort, 30% (95% CI, 24%-36%) of new cases of obesity and 43% (95% CI, 32%-52%) of new cases of diabetes could be prevented by adopting a relatively active lifestyle (

ContextStudies have shown an inverse relationship between exercise and risk of coronary heart disease (CHD), but data on type and intensity are sparse.ObjectiveTo assess the amount, type, and intensity of physical activity in relation to risk of CHD among men.Design, Setting, and ParticipantsA cohort of 44 452 US men enrolled in the Health Professionals' Follow-up Study, followed up at 2-year intervals from 1986 through January 31, 1998, to assess potential CHD risk factors, identify newly diagnosed cases of CHD, and assess levels of leisure-time physical activity.Main Outcome MeasureIncident nonfatal myocardial infarction or fatal CHD occurring during the follow-up period.ResultsDuring 475 755 person-years, we documented 1700 new cases of CHD. Total physical activity, running, weight training, and rowing were each inversely associated with risk of CHD. The RRs (95% confidence intervals [CIs]) corresponding to quintiles of metabolic equivalent tasks (METs) for total physical activity adjusted for age, smoking, and other cardiovascular risk factors were 1.0, 0.90 (0.78-1.04), 0.87 (0.75-1.00), 0.83 (0.71-0.96), and 0.70 (0.59-0.82) (P

Higher consumption of fish and omega-3 fatty acids has been associated with a lower risk of coronary heart disease (CHD) in men, but limited data are available regarding women.To examine the association between fish and long-chain omega-3 fatty acid consumption and risk of CHD in women.Dietary consumption and follow-up data from 84 688 female nurses enrolled in the Nurses' Health Study, aged 34 to 59 years and free from cardiovascular disease and cancer at baseline in 1980, were compared from validated questionnaires completed in 1980, 1984, 1986, 1990, and 1994.Incident nonfatal myocardial infarction and CHD deaths.During 16 years of follow-up, there were 1513 incident cases of CHD (484 CHD deaths and 1029 nonfatal myocardial infarctions). Compared with women who rarely ate fish (1 per month), those with a higher intake of fish had a lower risk of CHD. After adjustment for age, smoking, and other cardiovascular risk factors, the multivariable relative risks (RRs) of CHD were 0.79 (95% confidence interval [CI], 0.64-0.97) for fish consumption 1 to 3 times per month, 0.71 (95% CI, 0.58-0.87) for once per week, 0.69 (95% CI, 0.55-0.88) for 2 to 4 times per week, and 0.66 (95% CI, 0.50-0.89) for 5 or more times per week (P for trend =.001). Similarly, women with a higher intake of omega-3 fatty acids had a lower risk of CHD, with multivariable RRs of 1.0, 0.93, 0.78, 0.68, and 0.67 (P.001 for trend) across quintiles of intake. For fish intake and omega-3 fatty acids, the inverse association appeared to be stronger for CHD deaths (multivariate RR for fish consumption 5 times per week, 0.55 [95% CI, 0.33-0.90] for CHD deaths vs 0.73 [0.51-1.04]) than for nonfatal myocardial infarction.Among women, higher consumption of fish and omega-3 fatty acids is associated with a lower risk of CHD, particularly CHD deaths.

ContextPersuasive evidence has demonstrated that increased physical activity is associated with substantial reduction in risk of coronary heart disease. However, the role of physical activity in the prevention of stroke is less well established.ObjectiveTo examine the association between physical activity and risk of total stroke and stroke subtypes in women.Design and SettingThe Nurses' Health Study, a prospective cohort study of subjects residing in 11 US states.SubjectsA total of 72,488 female nurses aged 40 to 65 years who did not have diagnosed cardiovascular disease or cancer at baseline in 1986 and who completed detailed physical activity questionnaires in 1986, 1988, and 1992.Main Outcome MeasureIncident stroke occurring between baseline and June 1, 1994, compared among quintiles of physical activity level as measured by metabolic equivalent tasks (METs) in hours per week.ResultsDuring 8 years (560,087 person-years) of follow-up, we documented 407 incident cases of stroke (258 ischemic strokes, 67 subarachnoid hemorrhages, 42 intracerebral hemorrhages, and 40 strokes of unknown type). In multivariate analyses controlling for age, body mass index, history of hypertension, and other covariates, increasing physical activity was strongly inversely associated with risk of total stroke. Relative risks (RRs) in the lowest to highest MET quintiles were 1.00, 0.98, 0.82, 0.74, and 0.66 (P for trend=.005). The inverse gradient was seen primarily for ischemic stroke (RRs across increasing MET quintiles, 1.00, 0.87, 0.83, 0.76, and 0.52; P for trend=.003). Physical activity was not significantly associated with subarachnoid hemorrhage or intracerebral hemorrhage. After multivariate adjustment, walking was associated with reduced risk of total stroke (RRs across increasing walking MET quintiles, 1.00, 0.76, 0.78, 0.70, and 0.66; P for trend=.01) and ischemic stroke (RRs across increasing walking MET quintiles, 1.00, 0.77, 0.75, 0.69, and 0.60; P for trend=.02). Brisk or striding walking pace was associated with lower risk of total and ischemic stroke compared with average or casual pace.ConclusionThese data indicate that physical activity, including moderate-intensity exercise such as walking, is associated with substantial reduction in risk of total and ischemic stroke in a dose-response manner.

ContextAlthough many studies suggest that physical activity may reduce risk of type 2 diabetes, the role of moderate-intensity activity such as walking is not well understood.ObjectivesTo examine the relationship of total physical activity and incidence of type 2 diabetes in women and to compare the benefits of walking vs vigorous activity as predictors of subsequent risk of type 2 diabetes.Design and SettingThe Nurses' Health Study, a prospective cohort study that included detailed data for physical activity from women surveyed in 11 US states in 1986, with updates in 1988 and 1992.ParticipantsA total of 70,102 female nurses aged 40 to 65 years who did not have diabetes, cardiovascular disease, or cancer at baseline (1986).Main Outcome MeasureRisk of type 2 diabetes by quintile of metabolic equivalent task (MET) score, based on time spent per week on each of 8 common physical activities, including walking.ResultsDuring 8 years of follow-up (534,928 person-years), we documented 1419 incident cases of type 2 diabetes. After adjusting for age, smoking, alcohol use, history of hypertension, history of high cholesterol level, and other covariates, the relative risks (RRs) of developing type 2 diabetes across quintiles of physical activity (least to most) were 1.0, 0.77, 0.75, 0.62, and 0.54 (P for trend

In their meta-analysis of BMI and mortality �to inform decision making in the clinical setting,� Dr Flegal and colleagues1 found that mortality was not increased up to a BMI of less than 35.

Importance Loss-of-function mutations in the melatonin receptor are associated with insulin resistance and type 2 diabetes. Additionally, in a cross-sectional analysis of persons without diabetes, lower nocturnal melatonin secretion was associated with increased insulin resistance. Objective To study the association between melatonin secretion and the risk of developing type 2 diabetes. Design, Setting, and Participants Case-control study nested within the Nurses' Health Study cohort. Among participants without diabetes who provided urine and blood samples at baseline in 2000, we identified 370 women who developed type 2 diabetes from 2000-2012 and matched 370 controls using risk-set sampling. Main Outcome Measures Associations between melatonin secretion at baseline and incidence of type 2 diabetes were evaluated with multivariable conditional logistic regression controlling for demographic characteristics, lifestyle habits, measures of sleep quality, and biomarkers of inflammation and endothelial dysfunction. Results The median urinary ratios of 6-sulfatoxymelatonin to creatinine were 28.2 ng/mg (5%-95% range, 5.5-84.2 ng/mg) among cases and 36.3 ng/mg (5%-95% range, 6.9-110.8 ng/mg) among controls. Women with lower ratios of 6-sulfatoxymelatonin to creatinine had increased risk of diabetes (multivariable odds ratio, 1.48 [95% CI, 1.11-1.98] per unit decrease in the estimated log ratio of 6-sulfatoxymelatonin to creatinine). Compared with women in the highest ratio category of 6-sulfatoxymelatonin to creatinine, those in the lowest category had a multivariable odds ratio of 2.17 (95% CI, 1.18-3.98) of developing type 2 diabetes. Women in the highest category of melatonin secretion had an estimated diabetes incidence rate of 4.27 cases/1000 person-years compared with 9.27 cases/1000 person-years in the lowest category. Conclusions and Relevance Lower melatonin secretion was independently associated with a higher risk of developing type 2 diabetes. Further research is warranted to assess if melatonin secretion is a modifiable risk factor for diabetes within the general population.

Context Recent recommendations from the American Heart Association aim to improve cardiovascular health by encouraging the general population to meet 7 cardiovascular health metrics: not smoking; being physically active; having normal blood pressure, blood glucose and total cholesterol levels, and weight; and eating a healthy diet. Objective To examine time trends in cardiovascular health metrics and to estimate joint associations and population-attributable fractions of these metrics in relation to all-cause and cardiovascular disease (CVD) mortality risk. Design, Setting, and Participants Study of a nationally representative sample of 44 959 US adults (≥20 years), using data from the National Health and Nutrition Examination Survey (NHANES) 1988-1994, 1999-2004, and 2005-2010 and the NHANES III Linked Mortality File (through 2006). Main Outcome Measures All-cause, CVD, and ischemic heart disease (IHD) mortality. Results Few participants met all 7 cardiovascular health metrics (2.0% [95% CI, 1.5%-2.5%] in 1988-1994, 1.2% [95% CI, 0.8%-1.9%] in 2005-2010). Among NHANES III participants, 2673 all-cause, 1085 CVD, and 576 IHD deaths occurred (median follow-up, 14.5 years). Among participants who met 1 or fewer cardiovascular health metrics, age- and sex-standardized absolute risks were 14.8 (95% CI, 13.2-16.5) deaths per 1000 person-years for all-cause mortality, 6.5 (95% CI, 5.5-7.6) for CVD mortality, and 3.7 (95% CI, 2.8-4.5) for IHD mortality. Among those who met 6 or more metrics, corresponding risks were 5.4 (95% CI, 3.6-7.3) for all-cause mortality, 1.5 (95% CI, 0.5-2.5) for CVD mortality, and 1.1 (95% CI, 0.7-2.0) for IHD mortality. Adjusted hazard ratios were 0.49 (95% CI, 0.33-0.74) for all-cause mortality, 0.24 (95% CI, 0.13-0.47) for CVD mortality, and 0.30 (95% CI, 0.13-0.68) for IHD mortality, comparing participants who met 6 or more vs 1 or fewer cardiovascular health metrics. Adjusted population-attributable fractions were 59% (95% CI, 33%-76%) for all-cause mortality, 64% (95% CI, 28%-84%) for CVD mortality, and 63% (95% CI, 5%-89%) for IHD mortality. Conclusion Meeting a greater number of cardiovascular health metrics was associated with a lower risk of total and CVD mortality, but the prevalence of meeting all 7 cardiovascular health metrics was low in the study population.

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.

ContextDietary factors have been associated with the risk of developing colon cancer but the influence of diet on patients with established disease is unknown.ObjectiveTo determine the association of dietary patterns with cancer recurrences and mortality of colon cancer survivors.Design, Setting, and PatientsProspective observational study of 1009 patients with stage III colon cancer who were enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803) between April 1999 and May 2001. Patients reported on dietary intake using a semiquantitative food frequency questionnaire during and 6 months after adjuvant chemotherapy. We identified 2 major dietary patterns, prudent and Western, by factor analysis. The prudent pattern was characterized by high intakes of fruits and vegetables, poultry, and fish; the Western pattern was characterized by high intakes of meat, fat, refined grains, and dessert. Patients were followed up for cancer recurrence or death.Main Outcome MeasuresDisease-free survival, recurrence-free survival, and overall survival by dietary pattern.ResultsDuring a median follow-up of 5.3 years for the overall cohort, 324 patients had cancer recurrence, 223 patients died with cancer recurrence, and 28 died without documented cancer recurrence. A higher intake of a Western dietary pattern after cancer diagnosis was associated with a significantly worse disease-free survival (colon cancer recurrences or death). Compared with patients in the lowest quintile of Western dietary pattern, those in the highest quintile experienced an adjusted hazard ratio (AHR) for disease-free survival of 3.25 (95% confidence interval [CI], 2.04-5.19; P for trend

In their study of deaths associated with underweight, overweight, and obesity, Dr Flegal and colleagues1 conclude that excess mortality due to obesity and overweight is much lower than previously reported. We believe that their analysis is flawed and misleading. A major challenge in such studies is that low weight is often due to underlying chronic disease, which may exist for many years before death. Thus, lean persons are a mix of smokers, healthy active persons, and those with chronic illness (due to the direct effects of disease on weight and sometimes purposeful weight loss motivated by diagnosis of a serious illness). Their analysis does not successfully disentangle this diverse group.

ContextSugar-sweetened beverages like soft drinks and fruit punches contain large amounts of readily absorbable sugars and may contribute to weight gain and an increased risk of type 2 diabetes, but these relationships have been minimally addressed in adults.ObjectiveTo examine the association between consumption of sugar-sweetened beverages and weight change and risk of type 2 diabetes in women.Design, Setting, and ParticipantsProspective cohort analyses conducted from 1991 to 1999 among women in the Nurses' Health Study II. The diabetes analysis included 91 249 women free of diabetes and other major chronic diseases at baseline in 1991. The weight change analysis included 51 603 women for whom complete dietary information and body weight were ascertained in 1991, 1995, and 1999. We identified 741 incident cases of confirmed type 2 diabetes during 716 300 person-years of follow-up.Main Outcome MeasuresWeight gain and incidence of type 2 diabetes.ResultsThose with stable consumption patterns had no difference in weight gain, but weight gain over a 4-year period was highest among women who increased their sugar-sweetened soft drink consumption from 1 or fewer drinks per week to 1 or more drinks per day (multivariate-adjusted means, 4.69 kg for 1991 to 1995 and 4.20 kg for 1995 to 1999) and was smallest among women who decreased their intake (1.34 and 0.15 kg for the 2 periods, respectively) after adjusting for lifestyle and dietary confounders. Increased consumption of fruit punch was also associated with greater weight gain compared with decreased consumption. After adjustment for potential confounders, women consuming 1 or more sugar-sweetened soft drinks per day had a relative risk [RR] of type 2 diabetes of 1.83 (95% confidence interval [CI], 1.42-2.36; P

Nuts are high in unsaturated (polyunsaturated and monounsaturated) fat and other nutrients that may improve glucose and insulin homeostasis.To examine prospectively the relationship between nut consumption and risk of type 2 diabetes.Prospective cohort study of 83 818 women from 11 states in the Nurses' Health Study. The women were aged 34 to 59 years, had no history of diabetes, cardiovascular disease, or cancer, completed a validated dietary questionnaire at baseline in 1980, and were followed up for 16 years.Incident cases of type 2 diabetes.We documented 3206 new cases of type 2 diabetes. Nut consumption was inversely associated with risk of type 2 diabetes after adjustment for age, body mass index (BMI), family history of diabetes, physical activity, smoking, alcohol use, and total energy intake. The multivariate relative risks (RRs) across categories of nut consumption (never/almost never,once/week, 1-4 times/week, andor =5 times/week) for a 28-g (1 oz) serving size were 1.0, 0.92 (95% confidence interval [CI], 0.85-1.00), 0.84 (0.95% CI, 0.76-0.93), and 0.73 (95% CI, 0.60-0.89) (P for trend.001). Further adjustment for intakes of dietary fats, cereal fiber, and other dietary factors did not appreciably change the results. The inverse association persisted within strata defined by levels of BMI, smoking, alcohol use, and other diabetes risk factors. Consumption of peanut butter was also inversely associated with type 2 diabetes. The multivariate RR was 0.79 (95% CI, 0.68-0.91; P for trend.001) in women consuming peanut butter 5 times or more a week (equivalent toor =140 g [5 oz] of peanuts/week) compared with those who never/almost never ate peanut butter.Our findings suggest potential benefits of higher nut and peanut butter consumption in lowering risk of type 2 diabetes in women. To avoid increasing caloric intake, regular nut consumption can be recommended as a replacement for consumption of refined grain products or red or processed meats.

Although long or very irregular menstrual cycles may correlate with insulin resistance, it is not clear whether these irregularities predict a heightened future risk of type 2 (non-insulin-dependent) diabetes mellitus (DM). This study prospectively examined the risk of type 2 DM in 101,073 participants in the Nurses' Health Study II who had no history of diabetes and who described their menstrual pattern at age 18 to 22 years. Follow-up totalled 564,333 person-years, during which 507 cases of type 2 DM were identified. Normal cycles were those lasting 26 to 31 days; short cycles, less than 21 days; and long cycles, 40 days or more. Compared with women with cycles of normal length, the relative risk (RR) of type 2 DM was modestly but not significantly increased in those with short cycles. This remained the case after adjusting for age and body mass index at age 18, physical activity level, smoking status, oral contraceptive use, and a history of DM in a first-degree relative (multivariate RR, 1.50). The risk for women whose usual cycles lasted 32 to 39 days was very similar to the risk for those with cycles of 26 to 31 days. When cycles usually lasted 40 days or longer or were too irregular to estimate, the multivariate RR for type DM was 2.08. The risk of type 2 DM in women with long or very irregular cycles was greater in obese women, but it also was increased in those who were not obese. The findings were not substantially changed when adjusting for markers of androgen excess (eg, hirsutism or severe teenage acne), DM in a first-degree relative, and body mass index at age 18. The association between long or irregular cycles and a later diagnosis of type 2 DM also was not much altered when adjusting for race, past hypertension, antihypertensive therapy, or a history of infertility treatment. Prolonged or highly irregular menstrual cycles increase the risk of future type 2 DM, and this association is not entirely attributable to obesity. Possibly such menstrual irregularity is a marker for metabolic abnormalities. It may be these women who are especially likely to benefit from weight control and exercise.

ContextAlthough increased intake of grain products has been recommended to prevent cardiovascular disease (CVD), prospective data examining the relation of whole grain intake to risk of ischemic stroke are sparse, especially among women.ObjectiveTo examine the hypothesis that higher whole grain intake reduces the risk of ischemic stroke in women.Design, Setting, and ParticipantsA prospective cohort of 75,521 US women aged 38 to 63 years without previous diagnosis of diabetes mellitus, coronary heart disease, stroke, or other CVDs in 1984, who completed detailed food frequency questionnaires (FFQs) in 1984, 1986, 1990, and 1994, and were followed up for 12 years as part of the Nurses' Health Study.Main Outcome MeasureIncidence of ischemic stroke, confirmed by medical records, by quintile of whole grain intake according to FFQ responses.ResultsDuring 861,900 person-years of follow-up, 352 confirmed incident cases of ischemic stroke occurred. We observed an inverse association between whole grain intake and ischemic stroke risk. The age-adjusted relative risks (RRs) from the lowest to highest quintiles of whole grain intake were 1.00 (referent), 0.68 (95% confidence interval [CI], 0.49-0.94), 0.69 (95% CI, 0.51-0.95), 0.49 (95% CI, 0.35-0.69), and 0.57 (95% CI, 0.42-0.78; P = .003 for trend). Adjustment for smoking modestly attenuated this association (RR comparing extreme quintiles, 0.64; 95% CI, 0.47-0.89). This inverse association remained essentially unchanged with further adjustment for known CVD risk factors, including saturated fat and transfatty acid intake (multivariate-adjusted RR comparing extreme quintiles, 0.69; 95% CI, 0.50-0.98). The inverse relation between whole grain intake and risk of ischemic stroke was also consistently observed among subgroups of women who never smoked, did not drink alcohol, did not exercise regularly, or who did not use postmenopausal hormones. No significant association was observed between total grain intake and risk of ischemic stroke.ConclusionsIn this cohort, higher intake of whole grain foods was associated with a lower risk of ischemic stroke among women, independent of known CVD risk factors. These prospective data support the notion that higher intake of whole grains may reduce the risk of ischemic stroke.

ContextEpidemiological studies of men suggest that dietary fiber intake protects against coronary heart disease (CHD), but data on this association in women are sparse.ObjectiveTo examine the association between long-term intake of total dietary fiber as well as fiber from different sources and risk of CHD in women.Design and SettingThe Nurses' Health Study, a large, prospective cohort study of US women followed up for 10 years from 1984. Dietary data were collected in 1984, 1986, and 1990, using a validated semiquantitative food frequency questionnaire.ParticipantsA total of 68,782 women aged 37 to 64 years without previously diagnosed angina, myocardial infarction (MI), stroke, cancer, hypercholesterolemia, or diabetes at baseline.Main Outcome MeasureIncidence of acute MI or death due to CHD by amount of fiber intake.ResultsResponse rate averaged 80% to 90% during the 10-year follow-up. We documented 591 major CHD events (429 nonfatal MIs and 162 CHD deaths). The age-adjusted relative risk (RR) for major CHD events was 0.53 (95% confidence interval [CI], 0.40-0.69) for women in the highest quintile of total dietary fiber intake (median, 22.9 g/d) compared with women in the lowest quintile (median, 11.5 g/d). After controlling for age, cardiovascular risk factors, dietary factors, and multivitamin supplement use, the RR was 0.77 (95% CI, 0.57-1.04). For a 10-g/d increase in total fiber intake (the difference between the lowest and highest quintiles), the multivariate RR of total CHD events was 0.81 (95% CI, 0.66-0.99). Among different sources of dietary fiber (eg, cereal, vegetables, fruit), only cereal fiber was strongly associated with a reduced risk of CHD (multivariate RR, 0.63; 95% CI, 0.49-0.81 for each 5-g/d increase in cereal fiber).ConclusionsOur findings in women support the hypothesis that higher fiber intake, particularly from cereal sources, reduces the risk of CHD.

ContextReduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease (CHD). Epidemiologic studies on egg consumption and risk of CHD are sparse.ObjectiveTo examine the association between egg consumption and risk of CHD and stroke in men and women.Design and SettingTwo prospective cohort studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses' Health Study (1980-1994).ParticipantsA total of 37,851 men aged 40 to 75 years at study outset and 80,082 women aged 34 to 59 years at study outset, free of cardiovascular disease, diabetes, hypercholesterolemia, or cancer.Main Outcome MeasuresIncident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire.ResultsWe documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up. After adjustment for age, smoking, and other potential CHD risk factors, we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women. The relative risks (RRs) of CHD across categories of intake were less than 1 per week (1.0), 1 per week (1.06), 2 to 4 per week (1.12), 5 to 6 per week (0.90), and ≥1 per day (1.08) (P for trend=.75) for men; and less than 1 per week (1.0), 1 per week (0.82), 2 to 4 per week (0.99), 5 to 6 per week (0.95), and ≥1 per day (0.82) (P for trend=.95) for women. In subgroup analyses, higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects (RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men, 2.02 [95% confidence interval, 1.05-3.87; P for trend=.04], and among diabetic women, 1.49 [0.88-2.52; P for trend=.008]).ConclusionsThese findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women. The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research.