TY - JOUR
T1 - Effects of long-term vitamin D and n-3 fatty acid supplementation on inflammatory and cardiac biomarkers in patients with type 2 diabetes
T2 - secondary analyses from a randomised controlled trial
AU - Limonte, Christine P.
AU - Zelnick, Leila R.
AU - Ruzinski, John
AU - Hoofnagle, Andrew N.
AU - Thadhani, Ravi
AU - Melamed, Michal L.
AU - Lee, I. Min
AU - Buring, Julie E.
AU - Sesso, Howard D.
AU - Manson, Jo Ann E.
AU - de Boer, Ian H.
N1 - Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2021/2
Y1 - 2021/2
N2 - Aims/hypothesis: Interventions that reduce inflammation may delay progression of microvascular and macrovascular complications in diabetes. We examined the effects of vitamin D3 and/or n-3 fatty acid supplementation vs placebo on 5 year changes in serum inflammatory and cardiac biomarkers in adults with type 2 diabetes. 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 1312 US adults with type 2 diabetes and without known cardiovascular disease, malignancy, or end-stage kidney disease were randomised using computer-generated random numbers in blocks of eight to vitamin D3 (2000 IU/day) vs placebo and n-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]; 1 g/day) vs placebo in a 2 × 2 factorial design. Participants, examiners, and researchers assessing outcomes were blinded to intervention assignment. We measured serum IL-6, high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and after 2 and 5 years. Results: A total of 333 participants were randomised to vitamin D3 and placebo n-3 fatty acids, 289 to n-3 fatty acids and placebo vitamin D3, 370 to vitamin D3 and n-3 fatty acids, and 320 to 2 placebos; 989 (75%) and 934 (71%) participants returned blood samples at 2 and 5 years, respectively. Participants had a mean age of 67.6 years (46% women). Overall, baseline geometric means of IL-6, hsCRP and NT-proBNP were 1.2 pg/ml, 1.9 mg/l and 262 ng/l, respectively. After 5 years, mean IL-6 and hsCRP remained within 6% of their baseline values while mean NT-proBNP increased by 55% overall. Compared with placebo, participants assigned to vitamin D3 had a 1.24-fold greater increase in NT-proBNP over 5 years (95% CI 1.09, 1.41; p = 0.003), while IL-6 and hsCRP did not have a significant difference in change. Comparing n-3 fatty acids with placebo, there was no significant difference in change in IL-6, hsCRP or NT-proBNP. No heterogeneity was observed in subgroup analyses accounting for baseline eGFR, urine albumin to creatinine ratio, initial biomarker concentration, 25-hydroxyvitamin D level or EPA+DHA index. Conclusions/interpretation: Among adults with type 2 diabetes, supplementation with vitamin D3 or n-3 fatty acids did not reduce IL-6, hsCRP or NT-proBNP over 5 years. Trial registration: ClinicalTrials.gov NCT01684722 Funding: The study was funded by grant R01DK088762 from the National Institute of Diabetes and Digestive and Kidney Diseases. [Figure not available: see fulltext.]
AB - Aims/hypothesis: Interventions that reduce inflammation may delay progression of microvascular and macrovascular complications in diabetes. We examined the effects of vitamin D3 and/or n-3 fatty acid supplementation vs placebo on 5 year changes in serum inflammatory and cardiac biomarkers in adults with type 2 diabetes. 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 1312 US adults with type 2 diabetes and without known cardiovascular disease, malignancy, or end-stage kidney disease were randomised using computer-generated random numbers in blocks of eight to vitamin D3 (2000 IU/day) vs placebo and n-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]; 1 g/day) vs placebo in a 2 × 2 factorial design. Participants, examiners, and researchers assessing outcomes were blinded to intervention assignment. We measured serum IL-6, high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and after 2 and 5 years. Results: A total of 333 participants were randomised to vitamin D3 and placebo n-3 fatty acids, 289 to n-3 fatty acids and placebo vitamin D3, 370 to vitamin D3 and n-3 fatty acids, and 320 to 2 placebos; 989 (75%) and 934 (71%) participants returned blood samples at 2 and 5 years, respectively. Participants had a mean age of 67.6 years (46% women). Overall, baseline geometric means of IL-6, hsCRP and NT-proBNP were 1.2 pg/ml, 1.9 mg/l and 262 ng/l, respectively. After 5 years, mean IL-6 and hsCRP remained within 6% of their baseline values while mean NT-proBNP increased by 55% overall. Compared with placebo, participants assigned to vitamin D3 had a 1.24-fold greater increase in NT-proBNP over 5 years (95% CI 1.09, 1.41; p = 0.003), while IL-6 and hsCRP did not have a significant difference in change. Comparing n-3 fatty acids with placebo, there was no significant difference in change in IL-6, hsCRP or NT-proBNP. No heterogeneity was observed in subgroup analyses accounting for baseline eGFR, urine albumin to creatinine ratio, initial biomarker concentration, 25-hydroxyvitamin D level or EPA+DHA index. Conclusions/interpretation: Among adults with type 2 diabetes, supplementation with vitamin D3 or n-3 fatty acids did not reduce IL-6, hsCRP or NT-proBNP over 5 years. Trial registration: ClinicalTrials.gov NCT01684722 Funding: The study was funded by grant R01DK088762 from the National Institute of Diabetes and Digestive and Kidney Diseases. [Figure not available: see fulltext.]
KW - Biomarkers
KW - IL-6
KW - Inflammation
KW - NT-proBNP
KW - Type 2 diabetes
KW - Vitamin D
KW - hsCRP
KW - n-3 Fatty acids
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U2 - 10.1007/s00125-020-05300-7
DO - 10.1007/s00125-020-05300-7
M3 - Article
C2 - 33098434
AN - SCOPUS:85093514971
SN - 0012-186X
VL - 64
SP - 437
EP - 447
JO - Diabetologia
JF - Diabetologia
IS - 2
ER -