Longitudinal Changes in Fasting and Glucose-Stimulated GLP-1 and GIP in Healthy Older Subjects

J Clin Endocrinol Metab. 2019 Dec 1;104(12):6201-6206. doi: 10.1210/jc.2019-01262.


Context: It is not known whether glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels correlate within individuals, nor whether levels change with age. Previous studies have all been cross-sectional in design.

Objective: To evaluate longitudinal changes in fasting and glucose-stimulated incretin hormone concentrations in healthy older subjects.

Patients and design: Forty-one healthy older subjects had measurements of plasma GLP-1 and GIP while fasting and after a 75-g oral glucose load on two occasions separated by 5.9 ± 0.1 years [mean age at the initial study: 71.2 ± 3.8 (SD) years]. Breath samples were collected to calculate the gastric 50% emptying time (T50).

Results: For GLP-1, both fasting concentrations (P < 0.001) and area under the curve 0 to 120 minutes (P = 0.001) were decreased at followup. Fasting GIP was also lower (P = 0.03) at follow up, but there was no change in the area under the curve 0 to 120 minutes (P = 0.26). The gastric emptying T50 was slower at followup (P = 0.008). Neither the change in T50 nor the body mass index 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.

Conclusions: Fasting 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Blood Glucose / analysis*
  • Cross-Sectional Studies
  • Fasting*
  • Female
  • Follow-Up Studies
  • Gastric Inhibitory Polypeptide / blood*
  • Glucagon-Like Peptide 1 / blood*
  • Glucose Intolerance / blood*
  • Glucose Intolerance / physiopathology
  • Glucose Tolerance Test
  • Healthy Volunteers
  • Humans
  • Longitudinal Studies
  • Male
  • Prognosis


  • Biomarkers
  • Blood Glucose
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1