Longitudinal changes in fasting and glucose-stimulated GLP-1 and GIP in healthy older subjects.

Abstract

CONTEXT\nIt is not known whether GLP-1 and GIP levels correlate within individuals, nor whether levels change with age. Previous studies have all been cross-sectional in design.\n\n\nOBJECTIVE\nTo evaluate longitudinal changes in fasting and glucose-stimulated incretin hormone concentrations in healthy older subjects.\n\n\nPATIENTS AND DESIGN\n41 healthy older subjects had measurements of plasma GLP-1 and GIP while fasting and after a 75g oral glucose load on two occasions separated by 5.9 ± 0.1 years (mean age at the initial study was 71.2 ± 3.8 (SD) years). Breath samples were collected to calculate the gastric 50% emptying time (T50).\n\n\nRESULTS\nFor GLP-1, both fasting concentrations (P<0.001) and AUC0-120 (P=0.001) were decreased at follow-up. Fasting GIP was also lower (P=0.03) at follow-up, but there was no change in the AUC0-120 (P=0.26). The gastric emptying T50 was slower at follow-up (P=0.008). Neither the change in T50 nor the BMI at the initial study was a determinant of the change in incretin responses. Between the two study days, fasting GIP (r=0.72, P<0.001) correlated well, but not fasting GLP-1 (r=0.23, P=0.18). However, both glucose-stimulated GLP-1 (r=0.50, P=0.002) and GIP (r=0.60, P<0.001) showed correlations between the initial and follow-up studies.\n\n\nCONCLUSIONS\nFasting GIP, and glucose-stimulated GLP-1 and GIP concentrations correlate within individuals over a follow-up period of ∼ 5.9 years. Aging is associated with reductions in fasting GLP-1 and GIP, and glucose-stimulated GLP-1, which may predispose to the development of glucose intolerance and type 2 diabetes.