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Elevated Plasma Glucose-Dependent Insulinotropic Polypeptide Associates With Hyperinsulinemia in Impaired Glucose Tolerance

From the Diabetes Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland

Address correspondence and reprint requests to Josephine M. Egan, MD, Diabetes Section, NIA, NIH, 5600 Nathan Shock Dr., GRC-2B02, Baltimore, MD 21224. E-mail: eganj{at}vax.grc.nia.nih.gov

OBJECTIVE—The role of gut-derived incretin, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory peptide [GIP]), in compensatory ß-cell hypersecretion during insulin-resistant states and in transition to ß-cell failure in type 2 diabetes is unknown.

RESEARCH DESIGN AND METHODS—We carried out oral glucose tolerance testing followed by blood sampling 10 times for 2 h on 68 age- and BMI-matched participants of the Baltimore Longitudinal Study on Aging (BLSA) with normal glucose tolerance (34 subjects), impaired glucose tolerance (IGT) (18 subjects with both impaired fasting and 2-h plasma glucose levels), and type 2 diabetes (16 subjects with both diabetic fasting and 2-h plasma glucose levels). We assayed plasma glucose, insulin, C-peptide, glucagon, and intact and total GIP levels and quantitated glucose and hormone responses to the oral glucose tolerance test. We also compared GIP and insulin release and sensitivity indexes between groups.

RESULTS—After glucose ingestion, subjects with IGT had both hyperinsulinemia and hyperemia, while subjects with type 2 diabetes had both ß- and GIP-cell deficiency. In the former group, there was also a significant positive correlation between the augmented plasma intact and total GIP levels and both fasting and post-oral glucose load plasma insulin levels.

CONCLUSIONS— Elevated plasma GIP levels are correlated with hyperinsulinemia in the impaired glucose-tolerant state, whereas type 2 diabetes is associated with a failure to secrete adequate amounts of both GIP and insulin, indicating a common pathway of resistance to and eventually failure of glucose responsiveness in ß- and GIP-cells.

Abbreviations: AUC, area under the curve • BLSA, Baltimore Longitudinal Study on Aging • GIP, glucose-dependent insulinotropic polypeptide • GLP-1, glucagon-like peptide-1 • IGT, impaired glucose tolerance • OGTT, oral glucose tolerance test

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