Background: Immune system activation contributes to the development of microvascular and macrovascular complications in diabetes. Identifying interventions that reduce inflammation may delay progression of diabetes complications.

Methods: This study reports pre-specified secondary outcomes of the Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease, in which 1,312 adults with type 2 diabetes were randomized to vitamin D3 (2000 IU/d) versus placebo and omega-3 fatty acids (EPA+DHA;1g/d) versus placebo in a 2x2 factorial design. We measured serum interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and after two and five years, then used linear mixed models to test treatment effects.

Results: Participants were on average 67.6 years old (46% women). Overall, baseline geometric means of IL-6, hsCRP, and NT-proBNP were 1.2 pg/mL, 1.9 mg/L, and 262 pg/mL, respectively. After five years, mean IL-6 and hsCRP remained within 5% of their baseline values while mean NT-proBNP increased by 56% in the full population. Compared with placebo, participants assigned to vitamin D3 had a larger increase in NT-proBNP over time (ratio of change compared with placebo at five years 1.25; 95%CI 1.09-1.43; p=0.005), while there was no significant difference in change in IL-6 (ratio 0.97; 95%CI 0.80-1.18) or hsCRP (ratio 0.90; 95%CI 0.79-1.02). Comparing omega-3 fatty acids to placebo, there was no significant difference in change in IL-6 (ratio 1.11; 95%CI 0.92-1.34), hsCRP (ratio 0.88; 95%CI 0.77-1.00), or NT-proBNP (ratio 1.03; 95%CI 0.90-1.17) at five years. No heterogeneity was observed in subgroup analyses accounting for pre-specified clinical and demographic features.

Conclusions: Among adults with type 2 diabetes, supplementation with vitamin D3 or omega-3 fatty acids did not reduce IL-6, hsCRP, or NT-proBNP long-term.

Disclosure

C. Limonte: None. L. Zelnick: None. A. Hoofnagle: None. R. Thadhani: None. M. Melamed: Other Relationship; Self; American Board of Internal Medicine, ICON plc. J. Ruzinski: None. I. Lee: None. H. Sesso: None. J.E. Buring: Advisory Panel; Spouse/Partner; Pharmavite. J.E. Manson: None. I. de Boer: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Consultant; Self; George Clinical, Goldfinch Bio, Ironwood Pharmaceuticals.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK088762); National Institutes of Health (U01CA138962, R01CA138962)

© 2020 by the American Diabetes Association
2020
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