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

Abstract

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.

Effects of Age on Acute Appetite-Related Responses to Whey-Protein Drinks, Including Energy Intake, Gastric Emptying, Blood Glucose, and Plasma Gut Hormone Concentrations—A Randomized Controlled Trial

“…Plasma GLP-1 concentrations were lower at baseline in the older men compared to the younger men but increased more in the older men compared to the younger men after the nutrient drinks, as previously reported [41,42]. A recently published longitudinal study measured GLP-1 concentrations within the same healthy older participants~6 years apart, and found decreased fasting GLP-1 at the follow up compared to the initial study [43]. Similar to CCK, GLP-1 also has satiating effects [39]; however, the sensitivity to GLP-1 in the older population has not been evaluated.…”

Increasing Age Associated with Higher Dipeptidyl Peptidase-4 Inhibition Rate Is a Predictive Factor for Efficacy of Dipeptidyl Peptidase-4 Inhibitors

“…Other longitudinal study showed that a low tertile of GLP-1 response to the oral glucose tolerance test was associated with a steeper increase in fasting glucose level than higher tertiles during 7 years of follow-up [ 23 ]. A recent longitudinal study showed that fasting GIP and GLP-1 and glucose-stimulated GLP-1 decreased significantly over a mean period of 5.9 years and suggested that reduction in incretin hormone responses with aging may predispose one to the glucose intolerance and T2DM [ 24 ]. A major mechanism of action of DPP-4 inhibitors is potentiation of β-cell insulin secretion and inhibition of glucagon secretion by elevating endogenous GLP-1 in a glucosedependent mode of action [ 25 ].…”

Novel Insights into the Roles and Mechanisms of GLP-1 Receptor Agonists against Aging-Related Diseases

“…Moreover, the number is expected to increase to 195.2 million by 2030 and 276.2 million by 2045 [ 42 ]. GLP-1 levels can also be reduced by aging in a fasting and glucose-stimulated state [ 43 ]. However, GLP-1 can reverse the age-associated impairment of insulin sensitivity and glucose tolerance [ 44 , 45 ].…”