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

Bao, Xue LU ; Borné, Yan LU ; Muhammad, Iram Faqir LU ; Nilsson, Jan LU ; Lind, Lars; Melander, Olle LU ; Niu, Kaijun; Orho-Melander, Marju LU and Engström, Gunnar LU (2019) In Diabetologia 62(1). p.78-86
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cohort analysis, Diabetes mellitus, Growth differentiation factor 15, Macrophage inhibitory cytokine-1
in
Diabetologia
volume
62
issue
1
pages
9 pages
publisher
Springer
external identifiers
  • scopus:85058012898
ISSN
0012-186X
DOI
10.1007/s00125-018-4751-7
language
English
LU publication?
yes
id
09923019-541a-4110-ad98-d68d64f0ee32
date added to LUP
2018-12-18 12:18:33
date last changed
2019-01-14 07:38:57
@article{09923019-541a-4110-ad98-d68d64f0ee32,
  abstract     = {<p>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 &lt; 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 (&gt;55 and ≤60) and &gt;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.</p>},
  author       = {Bao, Xue and Borné, Yan and Muhammad, Iram Faqir and Nilsson, Jan and Lind, Lars and Melander, Olle and Niu, Kaijun and Orho-Melander, Marju and Engström, Gunnar},
  issn         = {0012-186X},
  keyword      = {Cohort analysis,Diabetes mellitus,Growth differentiation factor 15,Macrophage inhibitory cytokine-1},
  language     = {eng},
  number       = {1},
  pages        = {78--86},
  publisher    = {Springer},
  series       = {Diabetologia},
  title        = {Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus : the Malmö Diet and Cancer–Cardiovascular Cohort},
  url          = {http://dx.doi.org/10.1007/s00125-018-4751-7},
  volume       = {62},
  year         = {2019},
}