Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

Marion Denos; Xiao-Mei Mai; Bjørn Olav Åsvold; Elin Pettersen Sørgjerd; Yue Chen; Yi-Qian Sun

doi:10.1136/bmjdrc-2020-001948

Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

BMJ Open Diabetes Res Care. 2021 Jan;9(1):e001948. doi: 10.1136/bmjdrc-2020-001948.

Authors

Marion Denos¹, Xiao-Mei Mai¹, Bjørn Olav Åsvold^{2

3}, Elin Pettersen Sørgjerd⁴, Yue Chen⁵, Yi-Qian Sun^{6

7

8}

Affiliations

¹ Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
² K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
³ Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
⁴ HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
⁵ School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
⁶ Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway yi-qian.sun@ntnu.no.
⁷ Department of Pathology, Clinic of Laboratory Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
⁸ Center for Oral Health Services and Research Mid-Norway (TkMidt), Trondheim, Norway.

Abstract

Introduction: We sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.

Research design and methods: This prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995-1997) and HUNT3 (2006-2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).

Results: Over 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).

Conclusion: Serum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

Keywords: epidemiology; genetic predisposition to disease; vitamin D.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cohort Studies
Diabetes Mellitus, Type 2* / epidemiology
Diabetes Mellitus, Type 2* / genetics
Genetic Predisposition to Disease
Humans
Incidence
Norway / epidemiology
Prospective Studies
Risk Factors
Vitamin D

Substances

Vitamin D