Nicola M. McKeown

Plasma 25-Hydroxyvitamin D Is Associated with Markers of the Insulin Resistant Phenotype in Nondiabetic Adults

We examined the cross-sectional association between plasma 25-hydroxyvitamin D [25(OH)D] and markers of the insulin resistant phenotype. Plasma 25(OH)D concentrations were measured in 808 nondiabetic participants of the Framingham Offspring Study. Outcome measures included fasting and 2-h post 75-g oral glucose tolerance test (OGTT) glucose and insulin; these were used to calculate the homeostatic model assessment-insulin resistance (HOMA-IR) and insulin sensitivity index (ISI(0,120)). We also measured plasma adiponectin, triacylglycerol, and HDL cholesterol concentrations as markers of the insulin-resistant phenotype. After adjusting for age, sex, BMI, waist circumference, and current smoking status, plasma 25(OH)D concentration was inversely associated with fasting plasma glucose and insulin concentrations, and HOMA-IR. Compared with the participants in the lowest tertile category of plasma 25(OH)D, those in the highest tertile category had a 1.6% lower concentration of fasting plasma glucose (P-trend = 0.007), 9.8% lower concentration of fasting plasma insulin (P-trend = 0.001), and 12.7% lower HOMA-IR score (P-trend < 0.001). After adjusting for age and sex, plasma 25(OH)D was positively associated with ISI(0,120), plasma adiponectin, and HDL cholesterol and inversely associated with plasma triacylglycerol, but these associations were no longer significant after further adjustment for BMI, waist circumference, and current smoking status. 25(OH)D and 2-h post-OGTT glucose were not associated. Among adults without diabetes, vitamin D status was inversely associated with surrogate fasting measures of insulin resistance. These results suggest that vitamin D status may be an important determinant for type 2 diabetes mellitus.

Mediterranean-style dietary pattern, reduced risk of metabolic syndrome traits, and incidence in the Framingham Offspring Cohort

BACKGROUND The benefit of the Mediterranean-style dietary pattern in mitigating metabolic risk factors for type 2 diabetes and cardiovascular disease has not been well investigated among nondiabetic Americans. OBJECTIVE The aim of this study was to examine the prospective association between the Mediterranean-style dietary pattern and metabolic syndrome. DESIGN The Mediterranean-style dietary pattern score (MSDPS) was used to characterize a Mediterranean-style dietary pattern in the Framingham Heart Study Offspring Cohort. We examined the longitudinal association between MSDPS and metabolic syndrome traits (including homeostasis model assessment-insulin resistance, fasting glucose, waist circumference, triglyceride, HDL cholesterol, and systolic and diastolic blood pressure) among 2730 participants of the Framingham Heart Study Offspring Cohort without type 2 diabetes (baseline median age: 54 y; 55% women), who were followed from the fifth (baseline) to the seventh study examinations (mean follow-up time: 7 y), and metabolic syndrome incidence (according to the National Cholesterol Education Program Adult Treatment Panel III definition) in 1918 participants free of the condition at baseline. RESULTS A higher MSDPS was associated with lower homeostasis model assessment-insulin resistance (P = 0.02), waist circumference (P < 0.001), fasting plasma glucose (P = 0.03), and triglycerides (P < 0.001) and higher HDL cholesterol (P = 0.02) after adjustment for the corresponding baseline values and for several confounding factors associated with type 2 diabetes risk. Participants in the highest quintile category of the MSDPS had a lower incidence of metabolic syndrome than those in the lowest quintile category (38.5% compared with 30.1%; P = 0.01). CONCLUSION Our study suggests that the consumption of a diet consistent with the principles of the Mediterranean-style diet may protect against metabolic syndrome in Americans.

Putting the Whole Grain Puzzle Together: Health Benefits Associated with Whole Grains—Summary of American Society for Nutrition 2010 Satellite Symposium

The symposium “Putting the Whole Grain Puzzle Together: Health Benefits Associated with Whole Grains” sponsored by the ASN brought together researchers to review the evidence regarding the health benefits associated with whole grains. Current scientific evidence indicates that whole grains play an important role in lowering the risk of chronic diseases, such as coronary heart disease, diabetes, and cancer, and also contribute to body weight management and gastrointestinal health. The essential macro- and micronutrients, along with the phytonutrients present in whole grains, synergistically contribute to their beneficial effects. Current evidence lends credence to the recommendations to incorporate whole grain foods into a healthy diet and lifestyle program. The symposium also highlighted the need for further research to examine the role of whole grain foods in disease prevention and management to gain a better understanding of their mechanisms of action.

Predicted 25-hydroxyvitamin D score and incident type 2 diabetes in the Framingham Offspring Study

BACKGROUND Accumulating evidence suggests that vitamin D is involved in the development of type 2 diabetes (T2D). OBJECTIVE Our objective was to examine the relation between vitamin D status and incidence of T2D. DESIGN We used a subsample of 1972 Framingham Offspring Study participants to develop a regression model to predict plasma 25-hydroxyvitamin D [25(OH)D] concentrations from age, sex, body mass index, month of blood sampling, total vitamin D intake, smoking status, and total energy intake. Using this model, we calculated the predicted 25(OH)D score for each nondiabetic participant at the cohorts fifth examination to assess the association between the predicted 25(OH)D score and incidence of T2D by using Cox proportional hazards models. RESULTS A total of 133 T2D cases were identified over a 7-y average follow-up. In comparison with individuals in the lowest tertile of the predicted 25(OH)D score at baseline, those in the highest tertile had a 40% lower incidence of T2D after adjustment for age, sex, waist circumference, parental history of T2D, hypertension, low HDL cholesterol, elevated triglycerides, impaired fasting glucose, and Dietary Guidelines for Americans Adherence Index score (hazard ratio: 0.60; 95% CI: 0.37, 0.97; P for trend = 0.03). CONCLUSIONS Our findings suggest that higher vitamin D status is associated with decreased risk of T2D. Maintaining optimal 25(OH)D status may be a strategy to prevent the development of T2D.

Interactions of dietary whole grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies

OBJECTIVE Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. RESEARCH DESIGN AND METHODS Via meta-analysis of data from 14 cohorts comprising ∼48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. RESULTS Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: −0.009 mmol/l glucose [−0.013 to −0.005], P < 0.0001 and −0.011 pmol/l [ln] insulin [−0.015 to −0.007], P = 0.0003). No interactions met our multiple testing–adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. CONCLUSIONS Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake

Background: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. Objective: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. Design: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 × 10−6 were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data. Results: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (β ± SE: 0.25 ± 0.04%; P = 1.68 × 10−8) and lower fat (β ± SE: −0.21 ± 0.04%; P = 1.57 × 10−9) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)–increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (β ± SE: 0.10 ± 0.02%; P = 9.96 × 10−10), independent of BMI (after adjustment for BMI, β ± SE: 0.08 ± 0.02%; P = 3.15 × 10−7). Conclusion: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

The Development of the Mediterranean-Style Dietary Pattern Score and Its Application to the American Diet in the Framingham Offspring Cohort

Previous Mediterranean diet scores were simple to apply but may not be appropriate for non-Mediterranean populations. We developed a Mediterranean-Style Dietary Pattern Score (MSDPS) to assess the conformity of an individuals diet to a traditional Mediterranean-style diet. The MSDPS is based on the recommended intakes of 13 food groups in the Mediterranean diet pyramid. Each food group is scored from 0 to 10 depending on the degree of correspondence with recommendations. Exceeding the recommendations results in a lower score proportional to the degree of overconsumption. The sum of the component scores is standardized to a 0-100 scale and weighted by the proportion of energy consumed from Mediterranean diet foods. We applied the MSDPS to dietary data collected at the 7th examination of the Framingham Offspring Cohort and tested the content validity of the score against selected nutrients known to be associated with the Mediterranean-style dietary pattern. The mean MSDPS was 24.8 (range, 3.1-60.7). Participants with a higher MSDPS were more likely to be women, older, multivitamin users, to have lower BMI and waist circumferences, and less likely to be current smokers. The MSDPS demonstrated content validity through expected positive associations with intakes of dietary fiber, (n-3) fatty acids, antioxidant vitamins, calcium, magnesium, and potassium, and inverse associations with those of added sugar, glycemic index, saturated fat, and trans-fat, and the (n-6):(n-3) fatty acid ratio. The MSDPS is a useful instrument to measure overall diet quality according to the principles of a Mediterranean-style dietary pattern.

Whole-Grain Intake and Cereal Fiber Are Associated with Lower Abdominal Adiposity in Older Adults

Foods high in dietary fiber may play an important role in regulating body weight. Few observational studies have examined the relationship between dietary fiber from different sources and body fat in older adults. Our objectives were to examine the associations among grain intake (whole and refined), dietary fiber and fiber sources, and body fat among older adults. We used data from 434 free-living adults (177 men and 257 women) aged between 60 and 80 y. Dietary intake was estimated from a 126-item semiquantitative FFQ. Percent body fat and percent trunk fat mass were measured by whole-body dual-energy X-ray absorptiometry. After adjustment for covariates, whole-grain intake was inversely associated with BMI [26.8 kg/m(2) (25.7-28.1) vs. 25.8 kg/m(2) (24.6-27.1), (95% CI); P-trend = 0.08], percent body fat [34.5% (32.7-36.3) vs. 32.1% (30.1-34.1); P-trend = 0.02], and percent trunk fat mass [43.0% (40.4-45.5) vs. 39.4% (36.7-42.1); P-trend = 0.02] in the lowest compared with the highest quartile category of whole-grain intake. Refined grain intake was not associated with any measure of body fat distribution. Cereal fiber was inversely associated with BMI [27.3 kg/m(2) (26.1-28.6) vs. 25.4 kg/m(2) (24.3-26.7); P-trend = 0.012], percent body fat [34.7% (32.8-36.6) vs. 31.5% (29.4-33.5); P-trend = 0.004], and percent trunk fat mass [42.8% (40.2-45.4) vs. 37.8% (35.0-40.6); P-trend = 0.001]. No significant association was observed between intakes of total fiber, vegetable or fruit fiber, and body composition measurements. Higher intakes of cereal fiber, particularly from whole-grain sources, are associated with lower total percent body fat and percent trunk fat mass in older adults.

Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant: A 14-Cohort Meta-analysis

OBJECTIVE Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for β-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. RESEARCH DESIGN AND METHODS We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes. RESULTS We observed a significant association of total zinc intake with lower fasting glucose levels (β-coefficient ± SE per 1 mg/day of zinc intake: −0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (β-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: −0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant. CONCLUSIONS Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels.

Longitudinal association between dairy consumption and changes of body weight and waist circumference: the Framingham Heart Study

Background:Dairy foods are nutrient dense and may be protective against long-term weight gain.Objective:We aimed to examine the longitudinal association between dairy consumption and annualized changes in weight and waist circumference (WC) in adults.Methods:Members of the Framingham Heart Study Offspring Cohort who participated in the fifth through eighth study examinations (1991–2008) were included in these analyses (3440 participants with 11 683 observations). At each exam, dietary intake was assessed by a validated food frequency questionnaire, and weight and WC were assessed following standardized procedures. Repeated measures models were used for the longitudinal analyses of annualized weight and waist circumference changes, adjusting for time-varying or invariant covariates.Results:On average, participants gained weight and WC during follow-up. Dairy intake increased across exams. After adjusting for demographic and lifestyle factors (including diet quality), participants who consumed ⩾3 servings per day of total dairy had 0.10 kg (±0.04) smaller annualized increment of weight (Ptrend=0.04) than those consuming <1 serving per day. Higher total dairy intake was also marginally associated with less WC gain (Ptrend=0.05). Similarly, participants who consumed ⩾3 servings per week of yogurt had a 0.10 kg (±0.04) and 0.13 cm (±0.05) smaller annualized increment of weight (Ptrend=0.03) and WC (Ptrend=0.008) than those consuming <1 serving per week, respectively. Skim/low-fat milk, cheese, total high-fat or total low-fat dairy intake were not associated with long-term change in weight or WC.Conclusion:Further longitudinal and interventional studies are warranted to confirm the beneficial role of increasing total dairy and yogurt intake, as part of a healthy and calorie-balanced dietary pattern, in the long-term prevention of gain in weight and WC.