Relationship of Serum Fibroblast Growth Factor 21 with Abnormal Glucose Metabolism and Insulin Resistance: The Baltimore Longitudinal Study of Aging

Context: The relationship of fibroblast growth factor 21 (FGF21) with glucose metabolism and insulin resistance has not been well characterized in community-dwelling adults. Objective: The objective of the study was to examine the relationship of FGF21 with glucose metabolism and insulin resistance. Design: Serum FGF21, fasting plasma glucose (FPG), glucose tolerance, and insulin resistance were measured in a cross-sectional study, 2002-2007. Setting: The study was the Baltimore Longitudinal Study of Aging, a natural history cohort study of aging in community-dwelling men and women. Participants: Seven hundred adults, mean age 63.3 yr, participated in the study. Main Outcome Measures: FPG, 2-h plasma glucose, homeostasis model of insulin resistance, whole-body insulin sensitivity (Matsuda index), glucose area under the curve (AUC), and insulin AUC were measured. Results: Overall, the median (25th and 75th percentiles) FGF21 concentration was 225 (126, 370) pg/ml. The proportion of adults with normal, impaired, and diabetic FPG was 77.0, 21.4, and 1.6%, and those with normal, impaired, and diabetic 2-h plasma glucose was 76.7, 19.1, and 4.1%, respectively. Log serum FGF21 (picograms per milliliter), per 1 SD increase, was associated with an FPG (odds ratio 1.43, 95% confidence interval 1.15, 1.77, P = 0.001) and with 2-h plasma glucose (odds ratio 1.39, 95% confidence interval 1.12, 1.73, P = 0.003), in respective multivariate, ordered logistic regression models, adjusted for potential confounders. Serum FGF21 (picograms per milliliter) was associated with the homeostasis model of insulin resistance, the Matsuda index, glucose AUC, and insulin AUC (all P < 0.0001) in respective multivariable linear regression models adjusted for potential confounders. Conclusions: Higher serum FGF21 concentrations were associated with abnormal glucose metabolism and insulin resistance in community-dwelling adults. (J Clin Endocrinol Metab 97: 1375-1382, 2012)