Dairy consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis

We used data from three prospective cohort studies: HPFS, NHS and NHS II. The HPFS was composed of 51,529 US male dentists, pharmacists, veterinarians, optometrists, osteopathic physicians and podiatrists, 40- to 75-years old, who returned a baseline questionnaire that inquired about detailed medical history, as well as lifestyle and usual diet in 1986. The NHS was initiated in 1976, when 121,700 female registered nurses, 30- to 55-years old, who lived in one of eleven states, completed a baseline questionnaire about their lifestyle and medical history. The NHS II was established in 1989 and consisted of 116,671 younger female registered nurses, 25- to 42-years old, who responded to a baseline questionnaire similar to the NHS questionnaire. Detailed descriptions of the three cohorts have been published elsewhere [11]-[13]. In all three cohorts, questionnaires were administered at baseline and biennially thereafter, to collect and update information on lifestyle practice and occurrence of chronic diseases. The follow-up rates of the participants in these cohorts were all >90%. In the current analysis, we excluded men and women who had diagnoses of diabetes (including type 1 and type 2 diabetes and gestational diabetes only), cardiovascular disease, or cancer at baseline (1986 for HPFS, 1980 for NHS, and 1991 for NHS II, when we first assessed diet in these cohorts) [14]. In addition, we excluded participants who left >70 of the 131 food items blank on the baseline food frequency questionnaire (FFQ) or who reported unusual total energy intakes (that is, daily energy intake <800 or >4,200 kcal/day for men and <500 or >3,500 kcal/day for women). We also excluded participants without baseline information on dairy consumption or follow-up information on diabetes diagnosis date. After exclusions, data from 41,479 HPFS participants, 67,138 NHS participants and 85,884 NHS II participants were available for analysis. The study protocol was approved by the institutional review boards of Brigham and Women’s Hospital and Harvard School of Public Health. The completion of the self-administered questionnaire was considered to imply informed consent.

In 1980, a 61-item FFQ was administered to the NHS participants to collect information on their usual intake of foods and beverages in the previous year. In 1984, 1986, 1990, 1994, 1998 and 2002, similar but expanded 131-item FFQs were sent to these participants to update their diet records. With the use of the expanded FFQ used in the NHS, dietary data were collected in 1986, 1990, 1994, 1998 and 2002 from the HPFS participants, and in 1991, 1995, 1999 and 2003 from the NHS II participants.

In all FFQs, we asked the participants how often, on average, they consumed each food of a standard portion size. There were nine possible responses, which ranged from `never or less than once per month’ to `6 or more times per day’. Nutrient intake was calculated by multiplication of the frequency of consumption of each food by the nutrient composition in the standard portion size of that food and then summing up the nutrient intake from all relevant food items. The food composition database was created primarily from USDA sources [15]. Questionnaire items on dairy products included `skim/low fat milk’, `whole milk’, `ice cream’, `yogurt’, `cottage/ricotta cheese’, `cream cheese’, `other cheese’, `cream’. From 1994 in NHS and HPFS and 1995 in NHS II, yogurt consumption was separated into two items, `plain yogurt’ (plain or with NutraSweet) and `flavored yogurt’ (without NutraSweet). The standard serving size was an 8 oz. glass for skim, low fat milk, or whole milk, 1 Tbs for cream, sour cream, ½ cup for sherbet or frozen yogurt, ice cream, cottage or ricotta cheese, 1 oz. for cream cheese or other cheese. The reproducibility and validity of these FFQs have been shown in detail elsewhere [16]-[20]. The correlation coefficients between FFQ and multiple dietary records were 0.62 both for low-fat dairy foods and for high-fat dairy foods [20] and ranged from 0.57 for hard cheese to 0.97 for yogurt regarding various dairy products intakes [16].

In the biennial follow-up questionnaires, we inquired about and updated information on risk factors for chronic diseases, such as body weight, cigarette smoking, physical activity, medication use and family history of diabetes, as well as history of chronic diseases, including hypertension and hypercholesterolemia. Among NHS and II participants, we ascertained menopausal status, postmenopausal hormone use and oral contraceptive use.

A supplementary questionnaire about symptoms, diagnostic tests, and hypoglycemic therapy was mailed to participants who reported that they had received a diagnosis of diabetes. In accordance with National Diabetes Data Group criteria, a case of T2D was considered confirmed if at least one of the following was reported on the supplementary questionnaire [21]: 1) one or more classic symptoms (excessive thirst, polyuria, weight loss, hunger) and fasting plasma glucose concentrations ≥7.8 mmol/L or random plasma glucose concentrations ≥11.1 mmol/L; 2) ≥2 elevated plasma glucose concentrations on different occasions (fasting concentrations ≥7.8 mmol/L, random plasma glucose concentrations ≥11.1 mmol/L, and/or concentrations of ≥11.1 mmol/L after ≥2 hours shown by oral-glucose-tolerance testing) in the absence of symptoms; or 3) treatment with hypoglycemic medication (insulin or oral hypoglycemic agent). The diagnostic criteria were changed by the American Diabetes Association in June 1998, and the threshold for the diagnosis of diabetes became a fasting plasma glucose of 7.0 mmol/L, instead of 7.8 mmol/L [22]. Only cases confirmed by the supplemental questionnaires were included. The validity of the supplementary questionnaire for the diagnosis of diabetes has been documented previously. Of the 59 T2D cases in HPFS and 62 cases in NHS who were confirmed by the supplementary questionnaire, 57 (97%) and 61 (98%) were reconfirmed by medical records [23],[24]. Deaths were identified by reports from next of kin or postal authorities, or by searching the National Death Index. At least 98% of deaths among the study participants were identified [10].

We calculated each individual’s person-years from the date of return of the baseline questionnaire to the date of diagnosis of T2D, death, or the end of the follow-up (31 January 2010 for HPFS, 30 June 2010 for NHS or 30 June 2009 for NHS II), whichever came first. We used time-dependent Cox proportional hazard regression to estimate the hazard ratio (HR) for dairy consumption in relation to the risk of T2D. Our basic model (Model 1) simultaneously controlled for age, calendar time with updated information at each two-year questionnaire cycle, body mass index (BMI), and total energy intake. Model 2 also adjusted for various potential confounding factors, including race, smoking, physical activity, alcohol consumption, menopausal status and menopausal hormone use (NHS and II participants only), oral contraceptive use (NHS II participants only), family history of diabetes and diagnosed hypertension or hypercholesterolemia at baseline. Model 3 further adjusted for trans-fat, glycemic load, and intakes of red and processed meat, nuts, sugar-sweetened beverages (SSBs) and coffee. For individual dairy foods, we additionally adjusted for other types of dairy in model 3.

We used the cumulative average of dietary intakes from baseline to the censoring events in order to best represent long-term diet and minimize within-person variation [14]. In our primary analysis we stopped updating dietary intake when participants developed coronary heart disease, stroke or cancer because changes in diet after development of these conditions may confound the relationship between diet and diabetes [14],[25]. We conducted a further analysis by stopping updating dietary information after self-reported diagnosis of hypertension and hypercholesterolemia during the follow-up because these diagnoses appeared to alter consumption of dairy products (see Results).

We further conducted an updated meta-analysis that incorporated our new results from the three cohorts into the findings of previous studies. This meta-analysis was conducted following a review protocol [26]. For study selection, we included prospective studies with cohort, case cohort or nested case-control design investigating the association between intake of dairy products and risk of T2D. The two recent meta-analyses involved a search of the literature up to March 2013 [27] to June 2013 [8]. Thus, we conducted additional literature searches on MEDLINE [28] and EMBASE [29] from June 2013 to October 2013 [see Additional file 1]. In studies that reported the intakes by grams, we used 177 g as a serving size for total dairy products, and 244 g as a serving size for milk and yogurt intake to recalculate the intakes to a common scale (servings/day).