Date Published: October 10, 2018
Publisher: Public Library of Science
Author(s): Fumiaki Imamura, Amanda Fretts, Matti Marklund, Andres V. Ardisson Korat, Wei-Sin Yang, Maria Lankinen, Waqas Qureshi, Catherine Helmer, Tzu-An Chen, Kerry Wong, Julie K. Bassett, Rachel Murphy, Nathan Tintle, Chaoyu Ian Yu, Ingeborg A. Brouwer, Kuo-Liong Chien, Alexis C. Frazier-Wood, Liana C. del Gobbo, Luc Djoussé, Johanna M. Geleijnse, Graham G. Giles, Janette de Goede, Vilmundur Gudnason, William S. Harris, Allison Hodge, Frank Hu, Albert Koulman, Markku Laakso, Lars Lind, Hung-Ju Lin, Barbara McKnight, Kalina Rajaobelina, Ulf Risérus, Jennifer G. Robinson, Cécilia Samieri, David S. Siscovick, Sabita S. Soedamah-Muthu, Nona Sotoodehnia, Qi Sun, Michael Y. Tsai, Matti Uusitupa, Lynne E. Wagenknecht, Nick J. Wareham, Jason HY Wu, Renata Micha, Nita G. Forouhi, Rozenn N. Lemaitre, Dariush Mozaffarian, Andrew T Hattersley
Abstract: BackgroundWe aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D).Methods and findingsSixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance–weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73–0.87); of 17:0, 0.65 (0.59–0.72); of t16:1n7, 0.82 (0.70–0.96); and of their sum, 0.71 (0.63–0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist.ConclusionsIn a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D.
Partial Text: Regular consumption of dairy products is widely recommended in national and international guidelines as a major source of calcium and other minerals and vitamins as well as in low-income countries as a source of calories and protein. At least in high-income nations, fat-reduced dairy products are further recommended, rather than whole-fat products, with the aim of limiting calories and saturated fat . However, these latter recommendations are primarily based on nutrient profiles of low-fat and whole-fat dairy products rather than empirical evidence on clinical effects of dairy fat from prospective observational studies or trials [2–8]. In clinical trials, consuming low-fat or free-fat dairy products does not consistently improve intermediate risk factors compared to consuming whole-fat or overall dairy products [2–4]. In observational studies, total dairy consumption has not been associated with cardiovascular diseases, without consistent distinction based on dairy fat content. Regardless of fat content, total dairy consumption has been associated with lower incidence of type 2 diabetes (T2D) , whereas evidence is inconsistent for different types of dairy foods such as milk, yogurt, and cheese.
The 16 prospective studies (7 in the US, 7 in Europe, 1 in Australia, 1 in Taiwan) included 63,682 participants without known diabetes at baseline, among whom 15,180 incident T2D cases were identified during an average 9 years of follow-up (Table 1). All studies followed middle-aged or older adults with baseline mean age in each cohort ranging from 49 to 76 years. Average BMIs ranged from 25.0 to 28.4 kg/m2 except for Taiwan with an average BMI of 23.3 kg/m2. Most studies included predominantly white participants, although meaningful numbers of nonwhites were included in the Cardiovascular Health Study (CHS; 11.0% nonwhite), the Multi-Ethnic Study of Atherosclerosis (MESA; 71.6% nonwhite), the Women’s Health Initiative Memory Study (WHIMS; 11.6% nonwhite), and the Taiwanese study (100% Asian).
This harmonised pooling project of participant-level data among 16 prospective cohort studies provides, to our knowledge, the most comprehensive evidence for associations of biomarker levels of 15:0, 17:0, and t16:1n7 with risk of T2D. Comparing the top to the bottom quintile of participants in each cohort, we found that higher levels of the sum of these fatty acids were associated with approximately 30% lower risk of developing T2D. This relationship remained significant after adjustment for demographic characteristics, socioeconomic status, lifestyle factors, medical history, adiposity measures, and biomarkers of de novo lipogenesis.