Lyn M. Steffen

Dietary Intake and the Development of the Metabolic Syndrome The Atherosclerosis Risk in Communities Study

Background— The role of diet in the origin of metabolic syndrome (MetSyn) is not well understood; thus, we sought to evaluate the relationship between incident MetSyn and dietary intake using prospective data from 9514 participants (age, 45 to 64 years) enrolled in the Atherosclerosis Risk in Communities (ARIC) study. Methods and Results— Dietary intake was assessed at baseline via a 66-item food frequency questionnaire. We used principal-components analysis to derive “Western” and “prudent” dietary patterns from 32 food groups and evaluated 10 food groups used in previous studies of the ARIC cohort. MetSyn was defined by American Heart Association guidelines. Proportional-hazards regression was used. Over 9 years of follow-up, 3782 incident cases of MetSyn were identified. After adjustment for demographic factors, smoking, physical activity, and energy intake, consumption of a Western dietary pattern (Ptrend=0.03) was adversely associated with incident MetSyn. After further adjustment for intake of meat, dairy, fruits and vegetables, refined grains, and whole grains, analysis of individual food groups revealed that meat (Ptrend<0.001), fried foods (Ptrend=0.02), and diet soda (Ptrend=< 0.001) also were adversely associated with incident MetSyn, whereas dairy consumption (Ptrend=0.006) was beneficial. No associations were observed between incident MetSyn and a prudent dietary pattern or intakes of whole grains, refined grains, fruits and vegetables, nuts, coffee, or sweetened beverages. Conclusions— These prospective findings suggest that consumption of a Western dietary pattern, meat, and fried foods promotes the incidence of MetSyn, whereas dairy consumption provides some protection. The diet soda association was not hypothesized and deserves further study.

Genetic loci associated with plasma phospholipid N-3 fatty acids: A Meta-Analysis of Genome-Wide association studies from the charge consortium

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3×10−64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10−58) and docosapentaenoic acid (DPA, p = 4×10−154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10−12) and DPA (p = 1×10−43) and lower docosahexaenoic acid (DHA, p = 1×10−15). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10−8). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Background— Previous studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk. Methods and Results— We searched MEDLINE and EMBASE databases through June 2013 for prospective cohort studies that reported the association between dietary LA and CHD events. In addition, we used unpublished data from cohort studies in a previous pooling project. We pooled the multivariate-adjusted relative risk (RR) to compare the highest with the lowest categories of LA intake using fixed-effect meta-analysis. We identified 13 published and unpublished cohort studies with a total of 310 602 individuals and 12 479 total CHD events, including 5882 CHD deaths. When the highest category was compared with the lowest category, dietary LA was associated with a 15% lower risk of CHD events (pooled RR, 0.85; 95% confidence intervals, 0.78–0.92; I2=35.5%) and a 21% lower risk of CHD deaths (pooled RR, 0.79; 95% confidence intervals, 0.71–0.89; I2=0.0%). A 5% of energy increment in LA intake replacing energy from saturated fat intake was associated with a 9% lower risk of CHD events (RR, 0.91; 95% confidence intervals, 0.87–0.96) and a 13% lower risk of CHD deaths (RR, 0.87; 95% confidence intervals, 0.82–0.94). Conclusions— In prospective observational studies, dietary LA intake is inversely associated with CHD risk in a dose–response manner. These data provide support for current recommendations to replace saturated fat with polyunsaturated fat for primary prevention of CHD.

Food Omega-3 Fatty Acid Intake of Individuals (Total, Linolenic Acid, Long-Chain) and Their Blood Pressure. INTERMAP Study

Findings from short-term randomized trials indicate that dietary supplements of omega-3 polyunsaturated fatty acids (PFA) lower blood pressure of hypertensive persons, but effect size in nonhypertensive individuals is small and nonsignificant. Data are lacking on food omega-3 PFA and blood pressure in general populations. The International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) is an international cross-sectional epidemiologic study of 4680 men and women ages 40 to 59 from 17 population-based samples in China, Japan, United Kingdom, and United States. We report associations of food omega-3 PFA intake (total, linolenic acid, long-chain) of individuals with blood pressure. Systolic and diastolic blood pressure were measured 8 times at 4 visits. With several models to control for possible confounders (dietary, other), linear regression analyses showed inverse relationship of total omega-3 PFA from food (percent kilocalories, from four 24-hour dietary recalls) to systolic and diastolic blood pressures. With adjustment for 17 variables, estimated systolic blood pressure/diastolic blood pressure differences with 2 standard deviation higher (0.67% kcal) omega-3 PFA were −0.55/−0.57 mm Hg (Z-score −1.33, −2.00); for 2238 persons without medical or dietary intervention, −1.01/−0.98 mm Hg (Z −1.63, −2.25); for 2038 nonhypertensive persons from this sub-cohort, −0.91/−0.92 mm Hg (Z −1.80, −2.38). For linolenic acid (largely from vegetable foods), blood pressure differences were similar, eg, for the 2238 “nonintervened” individuals, −0.97/−0.87 mm Hg (Z −1.52, −1.95); blood pressure differences were −0.32/−0.45 mm Hg for long-chain omega-3 PFA (largely from fish). In summary, food omega-3 PFA intake related inversely to blood pressure, including in nonhypertensive persons, with small estimated effect size. Food omega-3 PFA may contribute to prevention and control of adverse blood pressure levels.

Dietary patterns and risk of incident type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVE—We characterized dietary patterns and their relation to incident type 2 diabetes in 5,011 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). RESEARCH DESIGN AND METHODS—White, black, Hispanic, and Chinese adults, aged 45–84 years and free of cardiovascular disease and diabetes, completed food frequency questionnaires at baseline (2000–2002). Incident type 2 diabetes was defined at three follow-up exams (2002–2003, 2004–2005, and 2005–2007) as fasting glucose >126 mg/dl, self-reported type 2 diabetes, or use of diabetes medication. Two types of dietary patterns were studied: four empirically derived (principal components analysis) and one author-defined (low-risk food pattern) as the weighted sum of whole grains, vegetables, nuts/seeds, low-fat dairy, coffee (positively weighted), red meat, processed meat, high-fat dairy, and soda (negatively weighted). RESULTS—The empirically derived dietary pattern characterized by high intake of tomatoes, beans, refined grains, high-fat dairy, and red meat was associated with an 18% greater risk (hazard ratio per 1-score SD 1.18 [95% CI 1.06–1.32]; Ptrend = 0.004), whereas the empirically derived dietary pattern characterized by high intake of whole grains, fruit, nuts/seeds, green leafy vegetables, and low-fat dairy was associated with a 15% lower diabetes risk (0.85 [0.76–0.95]; Ptrend = 0.005). The low-risk food pattern was also inversely associated with diabetes risk (0.87 [0.81–0.99]; Ptrend = 0.04). Individual component food groups were not independently associated with diabetes risk. Associations were not modified by sex or race/ethnicity. CONCLUSIONS—Multiple food groups collectively influence type 2 diabetes risk beyond that of the individual food groups themselves.

Whole grain intake and its cross-sectional association with obesity, insulin resistance, inflammation, diabetes and subclinical CVD: The MESA Study

We examined the relationship between whole grain intake and obesity, insulin resistance, inflammation, diabetes and subclinical CVD using baseline data from the Multi-Ethnic Study of Atherosclerosis. Whole grain intake was measured by a 127-item FFQ in 5496 men and women free of CHD and previously known diabetes. Mean whole grain intake was 0.5 (sd 0.5) servings per d; biochemical measures reflect fasting levels. After adjustment for demographic and health behaviour variables, mean differences for the highest quintile of whole grain intake minus the lowest quintile of intake were 0.6 kg/m2 for BMI, 0.36 mg/l for C-reactive protein, 0.82 micromol/l for homocysteine, 0.15 mU/l*mmol/l for homeostasis model assessment (HOMA), 0.48 mU/l for serum insulin, 2.0 mg/dl for glucose and 5.7 % for prevalence of newly diagnosed impaired fasting glucose (glucose >or= 100 mg/dl or diabetes medication). These differences represent 11-13 % of a standard deviation of BMI, HOMA, glucose and impaired fasting glucose, but 23 %, 52 % and 80 % of a standard deviation of homocysteine, C-reactive protein and insulin, respectively. An inverse association between whole grains and urine albumin excretion was suggested but retained statistical significance after adjustment only in Chinese and Hispanic participants. No associations were observed between whole grain intake and two subclinical disease measures: carotid intima-media thickness and coronary artery calcification. Concordant with previous research, whole grain intake was inversely associated with obesity, insulin resistance, inflammation and elevated fasting glucose or newly diagnosed diabetes. Counter to hypothesis, however, whole grain intake was unrelated to subclinical CVD.

Dietary linoleic acid and risk of coronary heart disease

Background— Previous studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk. Methods and Results— We searched MEDLINE and EMBASE databases through June 2013 for prospective cohort studies that reported the association between dietary LA and CHD events. In addition, we used unpublished data from cohort studies in a previous pooling project. We pooled the multivariate-adjusted relative risk (RR) to compare the highest with the lowest categories of LA intake using fixed-effect meta-analysis. We identified 13 published and unpublished cohort studies with a total of 310 602 individuals and 12 479 total CHD events, including 5882 CHD deaths. When the highest category was compared with the lowest category, dietary LA was associated with a 15% lower risk of CHD events (pooled RR, 0.85; 95% confidence intervals, 0.78–0.92; I2=35.5%) and a 21% lower risk of CHD deaths (pooled RR, 0.79; 95% confidence intervals, 0.71–0.89; I2=0.0%). A 5% of energy increment in LA intake replacing energy from saturated fat intake was associated with a 9% lower risk of CHD events (RR, 0.91; 95% confidence intervals, 0.87–0.96) and a 13% lower risk of CHD deaths (RR, 0.87; 95% confidence intervals, 0.82–0.94). Conclusions— In prospective observational studies, dietary LA intake is inversely associated with CHD risk in a dose–response manner. These data provide support for current recommendations to replace saturated fat with polyunsaturated fat for primary prevention of CHD.

Changes in Insulin Resistance and Cardiovascular Risk During Adolescence Establishment of Differential Risk in Males and Females

Background— Developmental changes in insulin resistance and cardiovascular risk were studied in youths 11 to 19 years of age. Methods and Results— A cohort was randomly selected after blood pressure screening of Minneapolis, Minn, school children. Studies were done 3 times on this cohort and once on their siblings (996 observations on 507 individuals from 363 families). Insulin sensitivity was determined by euglycemic clamp. Body mass index and waist circumference increased similarly in both sexes from ages 11 to 19 years. Body fat decreased in males and increased in females (P<0.001). Lean body mass increased at a steeper rate in males (P<0.0001). Insulin resistance was lower in males at 11 years but increased steadily to 19 years (P=0.003); in contrast, it did not increase in females. Thus, despite being less insulin resistant at 11 years and decreasing in fatness during puberty, males became more insulin resistant than females by 19 years of age. Triglycerides increased in males and high-density lipoprotein cholesterol decreased, whereas the opposite pattern was seen in females, which resulted in higher triglycerides and lower high-density lipoprotein cholesterol in males at 19 years. No gender difference in low-density lipoprotein or total cholesterol was seen. Systolic blood pressure increased in both sexes but at a greater rate in boys (P=0.03). Conclusions— During the transition from late childhood through adolescence, insulin resistance in males increased in association with increased triglycerides and decreased high-density lipoprotein cholesterol, despite a concurrent reduction in body fatness, whereas the opposite occurred in females. These gender-related developmental changes in insulin resistance, which were independent from changes in fatness, total cholesterol, and low-density lipoprotein cholesterol, are consistent with an early role for insulin resistance in the increased cardiovascular risk found in males.

Nonnutritive Sweeteners: Current Use and Health Perspectives A Scientific Statement From the American Heart Association and the American Diabetes Association

A 2009 American Heart Association scientific statement titled “Dietary Sugars Intake and Cardiovascular Health”1 concluded that current intake of added sugars among Americans greatly exceeds discretionary calorie allowances based on the 2005 US Dietary Guidelines.2 For this reason, the American Heart Association Nutrition Committee recommended population-wide reductions in added sugars intake. The present statement from the American Heart Association and the American Diabetes Association addresses the potential role of nonnutritive sweeteners (NNS) in helping Americans to adhere to this recommendation in the context of current usage and health perspectives. By definition, NNS, otherwise referred to as very low-calorie sweeteners, artificial sweeteners, noncaloric sweeteners, and intense sweeteners, have a higher intensity of sweetness per gram than caloric sweeteners such as sucrose, corn syrups, and fruit juice concentrates. As a caloric sweetener replacement, they are added in smaller quantities; hence, they provide no or few calories. In our current food supply, NNS are widely used in thousands of beverages and other food products such as diet soft drinks, yogurts, desserts, and gum. Food manufacturers often use a blend of NNS or use a blend of sugar and NNS to improve the flavor acceptability of NNS. In developing this scientific statement, the writing group reviewed issues pertaining to NNS in the context of data on consumer attitudes, consumption patterns, appetite, hunger and energy intake, body weight, and components of cardiometabolic syndrome. The objective was to review the literature to determine whether there were adequate data to provide guidance for the use of NNS. The focus of the statement is on the 6 NNS that are described in Table 1. Aspartame, acesulfame-K, neotame, saccharin, and sucralose are regulated as food additives by the US Food and Drug Administration and therefore had to be approved as safe before being marketed. Regarding stevia, …

Epidemiological support for the protection of whole grains against diabetes.

The epidemic of type 2 diabetes among children, adolescents and adults is increasing along with the increasing prevalence of overweight and obesity. Overweight is the most powerful modifiable risk factor for type 2 diabetes. Intake of wholegrain foods may reduce diabetes risk. Three prospective studies in 160000 men and women examined the relationship of whole-grain or cereal-fibre intake with the risk of type 2 diabetes. Each study used a mailed Willett food-frequency questionnaire and similar methods of quantifying wholegrain foods and cereal fibre. The self-reported incident diabetes outcome was more reliably determined in the two studies of health-care professionals than in the study of Iowa women. Risk for incident type 2 diabetes was 21-27% lower for those in the highest quintile of whole-grain intake, and 30-36% lower in the highest quintile of cereal-fibre intake, each compared with the lowest quintile. Risk reduction persisted after adjustment for the healthier lifestyle found among habitual whole-grain consumers. Observations in non-diabetic individuals support an inverse relationship between whole-grain consumption and fasting insulin levels. In feeding studies in non-diabetic individuals insulin resistance was reduced using whole grains or diets rich in whole grains. Glucose control improved with diets rich in whole grains in feeding studies of subjects with type 2 diabetes. There is accumulating evidence to support the hypothesis that whole-grain consumption is associated with a reduced risk of incident type 2 diabetes; it may also improve glucose control in diabetic individuals.