Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial.

Abstract

OBJECTIVE:

Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that is increased in obesity and established type 2 diabetes. We assessed whether GDF-15 can predict future insulin resistance and impaired glucose control in obese nondiabetic individuals.

DESIGN AND METHODS:

Plasma GDF-15 concentrations were measured with an automated electrochemiluminescent immunoassay at baseline and after 4 years in 496 obese nondiabetic individuals (52% men, median age 48 years, median body mass index (BMI) 37.6 kg/m(2)) enrolled in the XENical in the prevention of Diabetes in Obese subjects (XENDOS) trial.

RESULTS:

The median GDF-15 concentration at baseline was 869 ng/l (interquartile range 723-1064 ng/l). GDF-15 was related to body weight, BMI, waist-to-hip ratio, and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) (all P < 0.01). Changes in GDF-15 from baseline to 4 years were related to changes in body weight, BMI, waist-to-hip ratio, and HOMA-IR (all P < 0.05). Baseline GDF-15 was associated with the risk to have prediabetes or diabetes at 4 years by univariate analysis (odds ratio (OR) FOR 1 unit increase in ln GDF-15, 3.2; 95% confidence interval (CI): 1.7-6.1; P<0.001), and after multivariate adjustment for age, gender, treatment allocation (orlistat vs placebo), BMI, waist-to-hip ratio, and glucose control at baseline (OR 2.2; 95% CI: 1.1-4.7; P=0.026). Similarly, baseline GDF-15 was independently associated with HOMA-IR at 4 years (P=0.024).

CONCLUSIONS:

This first longitudinal study of GDF-15 in a large cohort of obese individuals indicates that GDF-15 is related to abdominal obesity and insulin resistance and independently associated with future insulin resistance and abnormal glucose control.

• Authors: Tibor Kempf, Anja Guba-Quint, Jarl Torgerson, Maria Chiara Magnone, Carolina Haefliger, Maria Bobadilla, Kai C Wollert
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 167 Issue 5 Pg. 671-8 (Nov 2012) ISSN: 1479-683X [Electronic] England
• PMID: 22918303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Blood Glucose
• Growth Differentiation Factor 15

Topics

• Adult
• Aged
• Analysis of Variance
• Biomarkers (blood)
• Blood Glucose (metabolism)
• Body Mass Index
• Cardiovascular Diseases (blood, etiology)
• Diabetes Mellitus (blood)
• Electrochemical Techniques
• Female
• Glucose Tolerance Test
• Growth Differentiation Factor 15 (blood)
• Humans
• Insulin Resistance
• Longitudinal Studies
• Luminescent Measurements
• Male
• Middle Aged
• Obesity (blood, metabolism)
• Odds Ratio
• Predictive Value of Tests
• Randomized Controlled Trials as Topic
• Risk Factors
• Time Factors
• Waist-Hip Ratio