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

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 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.

• Authors: Andrea Natali, Lorenzo Nesti, Elena Venturi, Angela C Shore, Faisel Khan, Kim Gooding, Phillip E Gates, Helen C Looker, Fiona Dove, Isabel Goncalves, Margaretha Persson, Jan Nilsson, SUMMIT consortium
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 21 Issue 2 Pg. 412-416 (02 2019) ISSN: 1463-1326 [Electronic] England
• PMID: 30178545 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• GDF15 protein, human
• Growth Differentiation Factor 15
• Metformin

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Cardiovascular Diseases (blood, diagnosis, epidemiology, prevention & control)
• Case-Control Studies
• Cohort Studies
• Diabetes Mellitus, Type 2 (blood, complications, drug therapy, epidemiology)
• Diabetic Angiopathies (blood, diagnosis, epidemiology, prevention & control)
• Female
• Growth Differentiation Factor 15 (blood)
• Humans
• Male
• Metformin (therapeutic use)
• Middle Aged
• Risk Factors