Dairy intake, plasma metabolome, and risk of type 2 diabetes in a population-based cohort

Abstract

Background: Whether dairy intake is related to type 2 diabetes (T2D) remains unclear, as does potential metabolic mechanisms for this association.

Objectives: We aimed to examine the association between high dairy intake and risk of T2D and identify plasma metabolites reflecting dairy intake.

Methods: This prospective cohort study included 26,461 Swedish individuals recruited between 1991 and 1996 and followed up until 31 December, 2020, with available data on dairy intake at baseline and linked registers. Plasma metabolites were measured in a subsample (n = 893) using mass spectrometry. Associations of dairy intake with risk of T2D were assessed using Cox proportional hazards models, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: A total of 4552 new-onset incident T2D cases were documented during a median follow-up of 24.3 y. Increased risk of T2D was observed among participants consuming high nonfermented milk (>1000 g/d compared with <200 g/d; HR: 1.40; 95% CI: 1.12, 1.74) and cheese (>100 g/d compared with <20 g/d; HR: 1.23; 95% CI: 1.07, 1.41), although decreased risk of T2D was observed among those with high fermented milk (>300 g/d compared with 0 g/d; HR: 0.88; 95% CI: 0.74, 1.03), cream (>50 g/d compared with <10 g/d; HR: 0.77; 95% CI: 0.64, 0.92), and butter (>50 g/d compared with 0 g/d; HR: 0.82; 95% CI: 0.71, 0.94). Such associations were slightly attenuated after additional adjustment for BMI. In addition, we identified metabolite profiles for nonfermented milk (n = 45), fermented milk (n = 48), cheese (n = 12), cream (n = 27), and butter (n = 46); no overlap between metabolites was found.

Conclusions: In this cohort of Swedish adults, high intakes of nonfermented milk and cheese are positively associated with risk of T2D, although high intakes of fermented milk, cream, and butter are inversely associated. Metabolomics provides novel insights into understanding the metabolic pathways of these associations.

Keywords: butter; cheese; cream; dairy; metabolites; metabolomics; milk; type 2 diabetes; yogurt.

FIGURE 1

Restricted cubic spline analysis of the association between dairy intake and risk of type 2 diabetes. Estimates were calculated in Cox proportional hazards models, adjusted for age, sex, dietary assessment version (method), season, total energy intake, leisure-time physical activity, alcohol consumption, smoking status, educational level, a family history of diabetes, lipid-lowering medication, hypertension at baseline, a personal history of cardiovascular disease, a personal history of cancer, fiber, vegetable and fruit, meat, soft drinks, and coffee. Solid lines are hazard ratios, and dashed lines are 95% CIs. The knots located at the 30th, 60th, and 90th percentiles of exposure and the lowest values of dairy intake (0 g/d) were used as the reference values. The distributions of dairy intake were winsorized at the 99.5 percentiles before modeling.

FIGURE 2

Heatmap showing Spearman correlation coefficients of individual metabolites related to dairy intake and dairy products as well as other foods: (A) nonfermented milk, (B) fermented milk, (C) cheese, (D) cream, and (E) butter.

FIGURE 3

Venn diagram showing the overlapping and different metabolites for 5 types of dairy products identified using elastic net regression models.

FIGURE 4

Heatmap showing Spearman correlation coefficients among dairy metabolite profile scores and dairy products as well as other foods.