Choi HK, Willett WC, Stampfer MJ, Rimm E, Hu FB. Dairy Consumption and Risk of Type 2 Diabetes Mellitus in MenA Prospective Study. Arch Intern Med. 2005;165(9):997-1003. doi:10.1001/archinte.165.9.997
Copyright 2005 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2005
Diet and lifestyle modifications can substantially reduce the risk of type 2 diabetes. While a strong inverse association has been reported between dairy consumption and the insulin resistance syndrome among young obese adults, the relation between dairy intake and type 2 diabetes is unknown.
We prospectively examined the relation between dairy intake and incident cases of type 2 diabetes in 41 254 male participants with no history of diabetes, cardiovascular disease, and cancer at baseline in the Health Professionals Follow-up Study.
During 12 years of follow-up, we documented 1243 incident cases of type 2 diabetes. Dairy intake was associated with a modestly lower risk of type 2 diabetes. After adjusting for potential confounders, including body mass index, physical activity, and dietary factors, the relative risk for type 2 diabetes in men in the top quintile of dairy intake was 0.77 (95% confidence interval [CI], 0.62-0.95; P for trend, .003) compared with those in the lowest quintile. Each serving-per-day increase in total dairy intake was associated with a 9% lower risk for type 2 diabetes (multivariate relative risk, 0.91; 95% CI, 0.85-0.97). The corresponding relative risk was 0.88 (95% CI, 0.81-0.94) for low-fat dairy intake and 0.99 (95% CI, 0.91-1.07) for high-fat dairy intake. The association did not vary significantly according to body mass index (<25 vs ≥25 kg/m2; P for interaction, .57).
Dietary patterns characterized by higher dairy intake, especially low-fat dairy intake, may lower the risk of type 2 diabetes in men.
Type 2 diabetes affects approximately 16 million people in the United States and 135 million people worldwide; the number of people with diabetes will reach an estimated 300 million worldwide by 2025.1,2 Because management of diabetes and its complications, such as cardiovascular disease, amputation, blindness, and renal failure, imposes enormous medical and economic burdens, primary prevention has become a public health imperative.1
Recent studies have shown that diet and lifestyle modifications are important means of preventing type 2 diabetes.1,3 Dairy consumption is a dietary factor that might affect type 2 diabetes. Several studies have suggested that dairy products may have favorable effects on body weight, the major determinant of type 2 diabetes.4- 6 In addition, a few studies, but not all, have suggested that dairy or calcium consumption was associated with lower risks for hypertension,7,8 coagulopathy,9 coronary artery disease,10,11 and stroke.12,13 An inverse cross-sectional association between dairy intake and insulin resistance syndrome (IRS) was observed in men.14 Furthermore, the Coronary Artery Risk Development in Young Adults (CARDIA) Study recently reported a strong inverse association between dairy consumption and IRS among young obese adults.15
To date, no published studies have examined the relation between dairy consumption and type 2 diabetes. Therefore, we prospectively evaluated the relation between dairy intake and incident type 2 diabetes in a large cohort of men.
The Health Professionals Follow-up Study is an ongoing longitudinal study of 51 529 male dentists, optometrists, osteopaths, pharmacists, podiatrists, and veterinarians who were 40 to 75 years of age in 1986. The participants returned a mailed questionnaire in 1986 concerning diet, medical history, and medications. We excluded men with implausibly high (>4200 kcal/d [>17 573 kJ/d) or low (<800 kcal/d [<3347 kJ/d]) total energy intake and/or blank responses for more than 70 of the 131 food items on the diet questionnaire. We also excluded men with a history of diabetes, cardiovascular disease (angina, coronary bypass or angioplasty, myocardial infarction, or stroke), or cancer (except for nonmelanoma skin cancer) because these diseases affect diet or reporting of diet. After these exclusions, 41 254 participants remained in the analysis.
To assess dietary intake, we used a semiquantitative food-frequency questionnaire that inquired about the average use of approximately 130 foods and beverages during the previous year.16,17 The baseline dietary questionnaire was completed in 1986 and was updated in 1990 and 1994. Nutrient intake was computed from the reported frequency of consumption of each specified unit of food or beverage and from published data on the nutrient content of the specified portions.17
Food and nutrient intakes assessed by this dietary questionnaire have been validated previously against two 1-week diet records in this cohort.16,18 The Pearson correlation coefficients for intake measured by two 1-week diet records and by the food-frequency questionnaire, adjusted for week-to-week variation in the diet records, were 0.62 both for low-fat dairy foods and for high-fat dairy foods.18
At baseline and every 2 years thereafter, participants provided information on body weight, regular use of medications, and medical conditions. Body mass index was calculated by dividing the weight in kilograms by the square of the height in meters. The follow-up for this cohort exceeded 90% during the study period.
We mailed a supplementary questionnaire on symptoms, diagnostic tests, and medication to all men who reported a diagnosis of diabetes on any of the biennial follow-up questionnaires (n = 2056). Confirmation of diabetes required at least one of the following: (1) an elevated plasma glucose concentration (fasting plasma glucose ≥140 mg/dL [≥7.8 mmol/L], random plasma glucose ≥200 mg/dL [≥11.1 mmol/L], and/or plasma glucose ≥200 mg/dL [≥11.1 mmol/L] after ≥2 hours during an oral glucose tolerance test) plus at least one classic symptom (excessive thirst, polyuria, weight loss, or hunger); (2) at least two elevated plasma glucose concentrations on different occasions; or (3) treatment with insulin or oral hypoglycemic medication. The diagnostic criteria for type 2 diabetes were changed in 1997.19 However, we used the criteria proposed by the National Diabetes Data Group20 because the vast majority of cases of diabetes in this study occurred before 1997. Men who reported that they had type 1 diabetes on the supplementary questionnaire were excluded. The validity of our assessment of type 2 diabetes was verified with medical records in a sample of 71 participants. A physician blinded to the information on the supplementary questionnaire reviewed the records according to the diagnostic criteria. Of the 71 participants who were classified as having type 2 diabetes, 12 had incomplete records (eg, absent laboratory data [n = 2] or only one set of laboratory data [n = 9]). Among the remaining 59 participants, the classification of type 2 diabetes was confirmed in 57 (97%). One patient denied having diabetes, and one lacked evidence of diabetes in his submitted records.
We computed person-time of follow-up for each participant from the return date of the 1986 questionnaire to the date of diagnosis of type 2 diabetes, death from any cause, or the end of the study period, whichever came first.
To represent long-term dairy intake patterns of individual subjects, we used cumulative average dairy intake based on information from the 1986, 1990, and 1994 dietary questionnaires.21 For example, the incidence of type 2 diabetes from 1986 through 1990 was related to dairy intake reported on the 1986 questionnaire, and incidence from 1990 through 1994 was related to the average intake reported on the 1986 and 1990 questionnaires. We repeated our analyses using baseline dairy intake (1986).
We used Cox proportional hazards modeling to estimate the relative risk (RR) for incident type 2 diabetes in all multivariate analyses (SAS Institute Inc, Cary, NC). Responses to the individual dairy items were converted to average daily number of servings of each item. The average daily intakes of individual dairy items were combined to compute dairy intake: low-fat dairy products, including skim/lowfat milk, sherbet, yogurt, and cottage/ricotta cheese; high-fat dairy foods, including whole milk, cream, sour cream, ice cream, cream cheese, and other cheese; and all dairy products, including all of the above. The average daily dairy intake was categorized into quintiles of intake and each quintile was compared with the lowest quintile. Multivariate models were adjusted for age (continuous), total energy intake (continuous), family history of diabetes (yes or no), smoking status (never smoked; former smoker; current smoker, 1-14 cigarettes per day; current smoker, 15-24 cigarettes per day; or current smoker, ≥25 cigarettes per day), body mass index (<23.0, 23.0-23.9, 24.0-24.9, 2.5-26.9, 2.7-28.9, 2.9-30.9, 31.0-34.9, or ≥35.0), hypercholesterolemia at baseline (yes or no), hypertension at baseline (yes or no), physical activity (quintiles of metabolic equivalent tasks [METs]), cereal fiber intake (quintiles), trans-fat intake (quintiles), ratio of polyunsaturated fat to saturated fat (quintiles), glycemic load (quintiles), and alcohol consumption (0, 0.1-4.9, 5.0-14.9, 15-29.9, or ≥30.0 g/d). We evaluated potential confounding by other possible dietary risk factors for type 2 diabetes (ie, nuts,1 processed meat,22 fruits,23 vegetables,23 coffee intake,24 Western dietary pattern,25 and prudent dietary pattern25) by entering each term (5 categories for coffee intake and quintiles for the others) into the multivariate model. The RR for the continuous measures indicates the change in risk associated with an average increment of one serving per day of the standard portion size. To assess the trends, we used the median values of intake for each category to minimize the influence of outliers. We conducted analyses stratified by body mass index (<25 vs ≥25), family history, or physical activity (<12.2 METs/wk [ie, median value] vs ≥12.2 METs/wk) to assess possible effect modification. We tested the significance of the interaction using the likelihood ratio test by comparing a model that included the main effects of dairy intake along with the stratifying variable and the interaction terms with a reduced model that included only the main effects. We calculated 95% confidence intervals (CIs) for all RRs. All P values are two sided.
The baseline characteristics of the cohort according to dairy consumption levels are shown in Table 1. Men with higher dairy intake tended to have slightly lower alcohol consumption, a higher level of physical activity, a less common history of hypertension and hypercholesterolemia, a higher intake of trans-fats, a higher glycemic load, a lower ratio of polyunsaturated fat to saturated fat, and higher intakes of fruits and vegetables. Other characteristics were similar across the quintile groups (Table 1).
During the 12-year follow-up, we documented 1243 incident cases of type 2 diabetes. After adjusting for age, the RR for men in the top quintile of total dairy intake was 0.82 (95% CI, 0.67-1.00; P for trend, .02) compared with those in the lowest quintile. After further adjustment for other risk factors, the association became stronger (RR, 0.77; 95% CI, 0.62-0.95; P for trend, .003) (Table 2). When we additionally adjusted for nuts, processed meat, fruits, vegetables, coffee consumption, and dietary patterns one at a time, the results did not materially change. Each serving-per-day increase in dairy intake was associated with a 9% lower risk for type 2 diabetes (multivariate RR, 0.91; 95% CI, 0.85-0.97). The associations were essentially the same using baseline information on dairy intake and covariates. Furthermore, when we limited our cases to only symptomatic cases (n = 763), the results did not materially change.
When we examined the association with dairy products stratified by their fat contents, the significant inverse association was primarily limited to low-fat dairy consumption (Table 3). Most individual low-fat dairy products and ice cream showed a similar inverse trend but only skim milk reached statistical significance (multivariate RR per serving, 0.90; 95% CI, 0.83-0.97) (Table 4).
When we additionally adjusted for total (or dietary) magnesium or potassium intake, our results did not materially change. There was a close correlation between dairy intake and total or dietary calcium intake (eg, Pearson correlation coefficient for low-fat dairy intake and dietary calcium, 0.79), and additional adjustment of these variables reduced the statistical significance of dairy intake, although the magnitude of association remained similar. For example, when we added dietary calcium intake in our multivariate model, the RR between the extreme quintiles was 0.76 (95% CI, 0.57-1.02; P for trend, .07) for low-fat dairy intake and 0.90 (95% CI, 0.63-1.28; P for trend, .55) for dietary calcium intake. However, when we adjusted for supplemental calcium, our results did not materially change.
The association between dairy intake and type 2 diabetes did not significantly vary by body mass index (<25 vs ≥25), family history, or physical activity (P>.50 for all) (Table 5).
In this large prospective cohort study of men, we found a modest inverse association between dairy consumption, especially low-fat dairy consumption, and incidence of type 2 diabetes. This association was independent of age, family history of diabetes, smoking, body mass index, physical activity, history of hypercholesterolemia and hypertension, and other known dietary risk factors for type 2 diabetes. Overall, the modest protective effect of dairy intake was consistent across different subgroups stratified by body mass index, physical activity, and family history of diabetes.
Dairy intake may protect against type 2 diabetes by favorably affecting known risk factors or precursors of the disease. Studies have suggested favorable effects on body weight,4- 6,15 hypertension,7,8,15 and abnormal glucose homeostasis.15 The CARDIA Study reported a strong inverse association between dairy intake and risk of IRS among young adults who were overweight (body mass index ≥25) but not among leaner individuals.15 In our study the association between dairy intake and type 2 diabetes did not vary significantly by body mass index, and the overall magnitude of the association (9% reduction in RR per serving increase in dairy foods) was notably smaller than the association with IRS shown among overweight young adults in the CARDIA Study (21%).15 Furthermore, in the CARDIA Study the association was present with both high-fat and low-fat dairy products but in our study it was limited to low-fat dairy intake. Potential explanations behind these differences (other than the outcome difference) include age difference (at the time of dairy exposure or outcome measurement) and dilution of effect in the later phases of the causal pathway toward type 2 diabetes. Regardless, the strong inverse association between dairy intake and risk of IRS in young adulthood shown in the CARDIA Study may not directly relate to risk of type 2 diabetes later in life.
The mechanism behind the inverse association between dairy intake and risk of type 2 diabetes remains unclear. Electrolytes in dairy foods, such as calcium and magnesium, may lower the risk of IRS and type 2 diabetes.15 When we additionally adjusted for these electrolytes, our results suggested that the association between dairy intake and type 2 diabetes was independent of these factors, although adjustment for dietary calcium was somewhat limited by its close correlation with dairy intake. Other major components in dairy products, such as lactose and dairy protein, may enhance satiety and reduce the risk of overweight and obesity (the major risk factor for type 2 diabetes) compared with other high-carbohydrate foods and beverages.15 However, saturated fat contained in dairy foods may mitigate these potential benefits, which may explain the weaker or null association with high-fat dairy foods observed in our study. While a lower glycemic index associated with dairy intake may reduce the risk of type 2 diabetes, our results showed an independent association after adjusting for glycemic load. Similarly, although lifestyle factors, including dietary patterns associated with dairy intake, may be responsible for lowering the risk, further adjustment for dietary patterns (Western vs prudent)25 did not materially affect our results.
For the potential public health application of our results, other potential benefits and risks associated with dairy intake should be taken into account. Studies have suggested that intake of low-fat dairy foods is associated with several potential health benefits, including lower incidence rates of coronary heart disease,26 premenopausal breast cancer,27 colon cancer,28 and gout.29 Furthermore, low-fat dairy foods are one of the main components of the Dietary Approaches to Stop Hypertension (DASH) diet, which has been shown to substantially lower blood pressure.30 However, dairy consumption, including low-fat dairy foods, has been implicated in possible increases in rates of prostate cancer.31 Further confirmation of these findings and comprehensive risk-benefit assessments are necessary before public health recommendations for dairy consumption can be made.
Several strengths and potential limitations of our study deserve comment. Although our study is observational, with the potential for unmeasured confounding as in all epidemiologic studies, the prospective design and high rate of follow-up minimized the possibility of recall bias and bias caused by loss to follow-up. Furthermore, the extensive information on potential confounders and the large study size allowed comprehensive adjustment of confounders. Self-reported diabetes was confirmed by a supplementary questionnaire, and validation with medical records indicated that reporting of diabetes was highly accurate in this medically knowledgeable population. Some underdiagnosis of diabetes is likely because screening for blood glucose was not feasible, given the size of the cohort. However, compared with the general population, the degree of underdiagnosis was probably smaller in this cohort of health professionals with ready access to medical care. Moreover, underascertainment of cases, if not associated with exposure, would not be expected to affect the RR estimates.32 Our findings are most directly generalizable to men 40 years old and older with no history of type 2 diabetes. Whether these findings apply to women or men with existing diabetes remains to be studied.
In conclusion, dietary patterns characterized by higher dairy intake, especially low-fat dairy intake, may lower the risk of type 2 diabetes.
Correspondence: Hyon K. Choi, MD, DrPH, Bulfinch 165, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114 (email@example.com).
Accepted for Publication: September 30, 2004.
Financial Disclosure: None.
Funding/Support: This work was supported in part by grants CA55075, HL35464, and HL65582 from the National Institutes of Health, Bethesda, Md.