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Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes : A nested, case–control study

, ; Natali, Andrea; Nesti, Lorenzo; Venturi, Elena; Shore, Angela C.; Khan, Faisel; Gooding, Kim; Gates, Phillip E.; Looker, Helen C. and Dove, Fiona, et al. (2019) In Diabetes, Obesity and Metabolism 21(2). p.412-416
Abstract

Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case–control study aimed at verifying whether biomarkers of atherosclerosis differ according to the presence of type 2 diabetes and cardiovascular disease. While in univariate analysis, major cardiovascular risk factors, with the exception of gender and cholesterol, increased similarly and linearly across GDF-15 quartiles, the independent variables associated with GDF-15, both in participants with... (More)

Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case–control study aimed at verifying whether biomarkers of atherosclerosis differ according to the presence of type 2 diabetes and cardiovascular disease. While in univariate analysis, major cardiovascular risk factors, with the exception of gender and cholesterol, increased similarly and linearly across GDF-15 quartiles, the independent variables associated with GDF-15, both in participants with and without diabetes, were age, plasma creatinine, N-terminal pro-brain natriuretic peptide, diuretic use, smoking exposure and glycated haemoglobin. In participants with diabetes, metformin treatment was associated with a 40% rise in GDF-15 level, which was independent of the other major factors, and largely explained their elevated GDF-15 levels. The relatively high GDF-15 bioavailability might partly explain the protective cardiovascular effects of metformin.

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Contribution to journal
publication status
published
subject
keywords
cardiovascular disease, GDF-15, growth differentiation factor-15, metformin, type 2 diabetes
in
Diabetes, Obesity and Metabolism
volume
21
issue
2
pages
412 - 416
publisher
Wiley-Blackwell
external identifiers
  • scopus:85054323416
ISSN
1462-8902
DOI
10.1111/dom.13519
language
English
LU publication?
yes
id
96c5e0ab-33d4-41d7-b60b-70fef43b99c7
date added to LUP
2018-11-08 12:19:04
date last changed
2019-02-20 11:34:52
@article{96c5e0ab-33d4-41d7-b60b-70fef43b99c7,
  abstract     = {<p>Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case–control study aimed at verifying whether biomarkers of atherosclerosis differ according to the presence of type 2 diabetes and cardiovascular disease. While in univariate analysis, major cardiovascular risk factors, with the exception of gender and cholesterol, increased similarly and linearly across GDF-15 quartiles, the independent variables associated with GDF-15, both in participants with and without diabetes, were age, plasma creatinine, N-terminal pro-brain natriuretic peptide, diuretic use, smoking exposure and glycated haemoglobin. In participants with diabetes, metformin treatment was associated with a 40% rise in GDF-15 level, which was independent of the other major factors, and largely explained their elevated GDF-15 levels. The relatively high GDF-15 bioavailability might partly explain the protective cardiovascular effects of metformin.</p>},
  author       = {,  and Natali, Andrea and Nesti, Lorenzo and Venturi, Elena and Shore, Angela C. and Khan, Faisel and Gooding, Kim and Gates, Phillip E. and Looker, Helen C. and Dove, Fiona and Goncalves, Isabel and Persson, Margaretha and Nilsson, Jan},
  issn         = {1462-8902},
  keyword      = {cardiovascular disease,GDF-15,growth differentiation factor-15,metformin,type 2 diabetes},
  language     = {eng},
  number       = {2},
  pages        = {412--416},
  publisher    = {Wiley-Blackwell},
  series       = {Diabetes, Obesity and Metabolism},
  title        = {Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes : A nested, case–control study},
  url          = {http://dx.doi.org/10.1111/dom.13519},
  volume       = {21},
  year         = {2019},
}