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


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.
Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Germany.
Tibor
T
Kempf
Anja
A
Guba-Quint
Jarl
J
Torgerson
Maria Chiara
MC
Magnone
Carolina
C
Haefliger
Maria
M
Bobadilla
Kai C
KC
Wollert
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D003920:Diabetes Mellitus / Q000097:blood*; D055664:Electrochemical Techniques; D005260:Female; D005951:Glucose Tolerance Test; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000378:metabolism; D016017:Odds Ratio; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013997:Time Factors; D049629:Waist-Hip Ratio
D015415:Biomarkers; D001786:Blood Glucose; D055436:Growth Differentiation Factor 15