Pathogenesis of Pre-Diabetes
Mechanisms of Fasting and Postprandial Hyperglycemia in People With Impaired Fasting Glucose and/or Impaired Glucose Tolerance
- Gerlies Bock1,
- Chiara Dalla Man2,
- Marco Campioni2,
- Elizabeth Chittilapilly1,
- Rita Basu1,
- Gianna Toffolo2,
- Claudio Cobelli2 and
- Robert Rizza1
- 1Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota
- 2Department of Electronics and Informatics, University of Padova, Padova, Italy
- Address correspondence and reprint requests to Robert A. Rizza, MD, Mayo Clinic, 200 1st St. SW, Rm 5-194 Joseph, Rochester, MN 55905. E-mail: rizza.robert{at}mayo.edu
Abstract
Thirty-two subjects with impaired fasting glucose (IFG) and 28 subjects with normal fasting glucose (NFG) ingested a labeled meal and 75 g glucose (oral glucose tolerance test) on separate occasions. Fasting glucose, insulin, and C-peptide were higher (P < 0.05) in subjects with IFG than in those with NFG, whereas endogenous glucose production (EGP) did not differ, indicating hepatic insulin resistance. EGP was promptly suppressed, and meal glucose appearance comparably increased following meal ingestion in both groups. In contrast, glucose disappearance (Rd) immediately after meal ingestion was lower (P < 0.001) in subjects with IFG/impaired glucose tolerance (IGT) and IFG/diabetes but did not differ in subjects with IFG/normal glucose tolerance (NGT) or NFG/NGT. Net insulin action (Si) and insulin-stimulated glucose disposal (Si*) were reduced (P < 0.001, ANOVA) in subjects with NFG/IGT, IFG/IGT, and IFG/diabetes but did not differ in subjects with NFG/NGT or IFG/NGT. Defective insulin secretion also contributed to lower postprandial Rd since disposition indexes were lower (P < 0.001, ANOVA) in subjects with NFG/IGT, IFG/IGT, and IFG/diabetes but did not differ in subjects with NFG/NGT and IFG/NGT. We conclude that postprandial hyperglycemia in individuals with early diabetes is due to lower rates of glucose disappearance rather than increased meal appearance or impaired suppression of EGP, regardless of their fasting glucose. In contrast, insulin secretion, action, and the pattern of postprandial turnover are essentially normal in individuals with isolated IFG.
- DI, disposition index
- EGP, endogenous glucose production
- IFG, impaired fasting glucose
- IGT, impaired glucose tolerance
- NFG, normal fasting glucose
- NGT, normal glucose tolerance
- OGTT, oral glucose tolerance test
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted September 6, 2006.
- Received March 9, 2006.
- DIABETES
