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Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus : the Malmö Diet and Cancer–Cardiovascular Cohort

Author:
  • Xue Bao
  • Yan Borné
  • Iram Faqir Muhammad
  • Jan Nilsson
  • Lars Lind
  • Olle Melander
  • Kaijun Niu
  • Marju Orho-Melander
  • Gunnar Engström
Publishing year: 2019
Language: English
Pages: 78-86
Publication/Series: Diabetologia
Volume: 62
Issue: 1
Document type: Journal article
Publisher: Springer

Abstract english

Aims/hypothesis: Growth differentiation factor 15 (GDF-15) is an anti-inflammatory cytokine of the transforming growth factor-β superfamily. Circulating levels of GDF-15 are associated with hyperglycaemia among people with obesity or diabetes, but longitudinal evidence on the association between GDF-15 levels and diabetes risk is scarce. Our aim was to explore whether circulating levels of GDF-15 at baseline are positively associated with future diabetes incidence in a middle-aged urban population. Methods: Between 1991 and 1994, baseline fasting plasma GDF-15 levels were measured in 4360 individuals without diabetes (mean age 57.4 ± 5.96 years, 38.6% men) who were participants in the Malmö Diet and Cancer–Cardiovascular Cohort. After a follow-up of 19.0 ± 5.16 years (mean ± SD), Cox proportional hazards regression analysis was used for the study of the relationship between baseline GDF-15 and incident diabetes, with adjustment for established confounders. A sensitivity analysis included further adjustment for levels of C-reactive protein (CRP). Results: During the follow-up period, 621 individuals developed diabetes. The multivariate-adjusted HR for diabetes incidence was 1.43 (95% CI 1.11, 1.83; p for trend = 0.007) for the fourth compared with the first quartile of GDF-15, and was 1.17 (95% CI 1.07, 1.28; p < 0.001) per SD increase of GDF-15. If participants were grouped according to baseline fasting glucose, the association between GDF-15 and diabetes risk was only evident in the group without impaired fasting glucose (n = 3973). The association tended to be less significant with increasing age: multivariate-adjusted HRs for diabetes per SD increase of GDF-15 were 1.24 (95% CI 1.08, 1.42), 1.19 (95% CI 1.00, 1.41) and 1.04 (95% CI 0.89, 1.23) for participants aged ≤55, 56–60 (>55 and ≤60) and >60 years, respectively. With adjustment for levels of CRP, the HR per SD increase of GDF-15 (1.21, 95% CI 1.09, 1.35) was significant (p = 0.015), but the HR for the fourth compared with the first quartile of GDF-15 was not significant (HR 1.30; 95% CI 1.01, 1.67; p for trend = 0.061). Conclusions/interpretation: GDF-15 may be useful for identification of people with a risk of incident diabetes, especially if those people are ≤60 years old.

Keywords

  • Endocrinology and Diabetes
  • Public Health, Global Health, Social Medicine and Epidemiology
  • Cohort analysis
  • Diabetes mellitus
  • Growth differentiation factor 15
  • Macrophage inhibitory cytokine-1

Other

Published
  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • ISSN: 0012-186X
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00