Risk of type 2 diabetes and cardiovascular disease is affected by a number of medical and lifestyle factors. In recent years, increasing attention has been focused on a constellation of risk factors termed the insulin resistance syndrome (IRS), also known as the metabolic syndrome or syndrome X. In this syndrome, obesity, insulin resistance, and hyperinsulinemia are thought to cause glucose intolerance, dyslipidemia (low serum high-density lipoprotein cholesterol (HDL-C), and high serum triglyceride concentrations), hypertension, and impaired fibrinolytic capacity. An increasing incidence of IRS in all racial, ethnic, and social class groups in the United States can be inferred from the increasing prevalence of obesity and type 2 diabetes over the last 3 decades. Recently, this syndrome has been observed in youth, and age-adjusted prevalence among adults has been estimated at 24%. An increase in the prevalence of IRS may partly explain the recent plateau or increase in cardiovascular disease rates, after several decades of decline.

Although various environmental influences, including smoking and physical inactivity, are known to promote insulin resistance, the effect of dietary composition on IRS is poorly understood. For most of the past 3 decades, the US Department of Agriculture and the American Heart Association have recommended low-fat diets in the prevention and treatment of cardiovascular disease. Recently, however, some have questioned these recommendations out of concern that high-carbohydrate consumption might promote IRS. Other dietary factors that have been linked to components of IRS include the ratios of monounsaturated or polyunsaturated to saturated fatty acids, dietary fiber, and glycemic index.

Dairy consumption is another dietary factor that might affect IRS. Milk intake has decreased significantly over the past 3 decades as the prevalence of obesity and type 2 diabetes has increased. Epidemiologic and experimental studies suggest that dairy products may have favorable effects on body weight in children and adults. In addition, dairy and/or calcium may decrease the risk for hypertension, coagulopathy, coronary artery disease, and stroke. An inverse cross-sectional association between dairy intake and IRS was observed in men but not in women although the influence of physical activity, fruit and vegetable intake, and other lifestyle factors was not considered. The purpose of this study was to examine, in a prospective fashion, the independent association between dairy consumption and IRS, after taking into account physical activity level, macronutrient and fiber intake, and other potentially confounding variables.

METHODS
The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a multicenter population-based prospective study of cardiovascular disease risk factor evolution in a US cohort of black and white young adults. The 4 study centers are Birmingham, Ala; Chicago, Ill; Minneapolis, Minn; and Oakland, Calif. Stratification was used to obtain nearly equal numbers of individuals in each race, age group (age ranges, 18-24 and 25-30 years), and educational level (high school diploma and <high school diploma). Participants have been followed up for 15 years, with the present analyses including the first 10 years and 5 clinic examinations beginning with the baseline in 1985 and including 1987, 1990, 1992, and 1995. Fifty-one percent of 5115 eligible participants underwent the baseline examination. Participation has been excellent at approximately 80% through 1995. More details of the CARDIA Study design and its participants have been reported.

Study Participants

From a total sample of 5115, we excluded from our analysis those who had no year 0 or year 7 dietary data (n = 1175); had unusually high or low dietary intake values (<800 and >8000 cal/d for men; <600 and >6000 cal/d for women), consistent with CARDIA procedures (n = 707); were pregnant at baseline or within 180 days of year 10 clinic examination (n = 184); or were taking medications that affect blood lipid levels (n = 87). Many participants belonged to more than 1 of these categories, leaving 3563 study participants. Two hundred sixty-five of these individuals had 2 or more components of the IRS at baseline, and 141 had missing IRS data, resulting in a final sample size of 3157. For stratified analyses, 923 of these individuals were overweight (body mass index [BMI] >=25 kg/m2).

Standard questionnaires were used to maintain consistency in the assessment of demographic (age, sex, race, educational level) and behavioral (physical activity and cigarette smoking) information across CARDIA examination visits. The CARDIA Physical Activity History questionnaire queries the amount of time per week spent in leisure, occupational, and household physical activities over the past 12 months. Physical activity level is summarized as units of total activity averaged from the baseline and year 7 examination. Educational level was quantified as the number of years of school completed by the year 10 examination, and cigarette smoking status as current vs other smoker at the baseline and year 7 examination.

Dietary Assessment

The CARDIA Diet History queries usual dietary practices and obtains a quantitative food frequency of the past 28 days. Starting with the Western Electric dietary history as a model, the list of foods was expanded from 150 to approximately 700 items in the hope of developing a dietary assessment tool that would be suitable across various populations and ethnic groups. Liu et al reported on the reliability and validity of the CARDIA Diet History in 128 young adults. The validity correlations between mean daily nutrient intakes from the CARDIA Diet History and means from 7 randomly scheduled 24-hour recalls were generally above 0.50. The correlations of calorie-adjusted calcium intake ranged from 0.56 to 0.69 across race and sex groups. After correction for within-person variability, they ranged from 0.66 to 0.80.

The University of Minnesota Nutrition Coordinating Center (NCC) tape 10 nutrient database was used at baseline and tape 20 at year 7. Foods containing dairy were identified by matching all CARDIA food codes to the entire NCC code listings for dairy products. We identified dairy products as any items reported during the diet history interview that were either 100% dairy (eg, milk) or included dairy as one of the main ingredients (eg, dips made with sour cream). We did not include mixed dishes or recipes when the contribution of dairy to the weight or caloric content of the item was unclear or likely to be minimal. The most frequently consumed dairy product at the baseline examination was milk and milk drinks, followed by butter, cream, and cheeses. Together these items comprised approximately 90% of dairy intake. Most of the remaining products were yogurts, dips, ice cream, and puddings and other dairy-based desserts. Weekly frequency of consumption for each food (times per week) was used to estimate relative intake per week for each food for each individual. In addition to using specific commonly consumed dairy foods, such as milk, as independent variables in our analyses, we also performed analyses for various dairy food groups based on type of product and amount of fat. Milk was considered to be reduced fat if it consisted of 2% milk fat whereas cheeses and desserts were considered to be reduced fat if they had less than 15% milk fat (eg, reduced fat sour cream). The summation of dairy intake across all foods in the respective food groups was computed for each individual. To improve the accuracy of estimating habitual intake, we averaged the intake reported during the interviews of the baseline and year 7 examinations. Total dairy intake was classified into 5 categories. To ensure sufficient numbers in each race per dairy category, approximate quintile cut points from the dairy distribution of the total cohort were used. Therefore, when stratified by race or baseline overweight status, we did not have equal numbers of observations per category.

We also considered intake of other food groups that may confound associations between dairy intake and IRS. These food groups included fruits, nonstarchy and starchy vegetables, fruit juices, soft drinks and sugar-sweetened beverages, whole and refined grains, meat, and fish. In attempt to maximize our adjustment for lifestyle factors that may confound associations between dairy intake and IRS, we created a healthy propensity score based on the following lifestyle factors, coded as 0 for unhealthy, and 1 for healthy: cigarette smoking (nonsmoker, 1), physical activity (above median total activity score, 1), fruit and vegetable intake (>=5 servings per day, 1), whole grain intake (above median intake level, 1), and soft drink consumption (below median intake level, 1). Thus, this healthy propensity score had a range of 0 (least healthy) to 5 (most healthy). We also created 2 groups among overweight individuals—those with a healthy propensity score below 3 (490/923) and those with a healthy propensity score of 3 or higher (433/923). Other dietary and nutrient measures from the CARDIA Diet History used in our analyses as potential confounders or mediators of our hypotheses included caloric intake; alcohol; fiber (grams per 1000 cal/d); caffeine (mg/d); percentage of calories from carbohydrates, protein, total fat, saturated and unsaturated fatty acids; and the micronutrients from supplements and foods including calcium, magnesium, sodium, potassium, and vitamin D.

COMMENT
We observed inverse associations between frequency of dairy intake and the development of obesity, abnormal glucose homeostasis, elevated blood pressure, and dyslipidemia in young overweight black and white men and women. The 10-year incidence of the IRS was lower by more than two thirds among overweight individuals in the highest category of dairy consumption (>=5/d) compared with those in the lowest category (<1.5/d). These associations were not confounded by other lifestyle factors or dietary variables that are correlated with dairy intake and did not differ materially by race or sex.

The main limitation of our study is its observational nature. Therefore, we cannot rule out residual confounding, and we cannot conclude that increased dairy intake reduced the incidence of IRS in a causal manner. The strengths of the study include its longitudinal design, allowing us to exclude participants with existing IRS at baseline and to compare the 10-year cumulative incidence of IRS across dairy categories from the average of 2 comprehensive diet history interviews. Self-reported diet averaged over time should be a better estimate of habitual intake than a single measure. Remaining errors in the measure of diet are likely to bias associations toward the null hypothesis (no association), resulting in an underestimation of the true magnitude of the association. Indeed, we observed somewhat stronger associations between dairy intake and IRS incidence when modeling the average dairy intake compared with the year 0 and year 7 dairy intake separately, although these differences were not large and do not materially affect the results or conclusions (data not shown). The diet history method was chosen for use in the CARDIA study because of its comprehensiveness, interviewer-administered format, suitable time-frame for capturing habitual diet without exacerbating recall error, and applicability to populations differing in social and cultural characteristics.

Although saturated fat contained in dairy products may raise LDL-C levels, there are several mechanisms by which dairy intake may protect against insulin resistance, obesity, and cardiovascular disease. Many single-nutrient studies, but not all, suggest that calcium, potassium, and magnesium may lower the risk of hypertension, coronary heart disease, stroke, or type 2 diabetes. Other studies have suggested an intracellular role of calcium or other components of dairy products in body weight regulation, a hypothesis supported by several, but not all, observational and experimental studies. In our study, the inverse association between calcium intake and IRS was entirely explained by dairy intake whereas the association between dairy consumption and IRS was not materially affected by adjustment for the intake of calcium or any other nutrients. It is also possible that the lactose, protein, and fat in dairy foods may enhance satiety and reduce the risk of overweight and obesity relative to other high-carbohydrate foods and beverages. However, adjustment for these nutrients also had no meaningful effect on the associations between dairy intake and the risk factors of the present study.

The CARDIA Study

Mark A. Pereira, PhD; David R. Jacobs, Jr, PhD; Linda Van Horn, PhD,RD; Martha L. Slattery, PhD,RD; Alex I. Kartashov, PhD; David S. Ludwig, MD,PhD

Corresponding Author and Reprints: Mark A. Pereira, PhD, Department of Medicine, Children’s Hospital, 300 Longwood Ave, Boston, MA 02115 (e-mail: .(JavaScript must be enabled to view this email address)).

Author Affiliations: Department of Medicine, Children’s Hospital, and Department of Pediatrics, Harvard Medical School (Drs Pereira and Ludwig), and Clinical Research Program, Children’s Hospital (Dr Kartashov), Boston, Mass; Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, and Institute for Nutrition Research, University of Oslo, Oslo, Norway (Dr Jacobs); Department of Preventive Medicine, Northwestern University Medical School, Chicago, Ill (Dr Van Horn); University of Utah Medical School, Salt Lake City (Dr Slattery).
JAMA. 2002;287:2081-2089.

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