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- Title
Pathogenesis of prediabetes: role of the liver in isolated fasting hyperglycemia and combined fasting and postprandial hyperglycemia.
- Authors
Basu, Rita; Barosa, Cristina; Jones, John; Dube, Simmi; Carter, Rickey; Basu, Ananda; Rizza, Robert A
- Abstract
<bold>Context: </bold>People with prediabetes are at high risk of developing diabetes.<bold>Objective: </bold>The objective of this study was to determine the pathogenesis of fasting and postprandial hyperglycemia in prediabetes.<bold>Design: </bold>Glucose production, gluconeogenesis, glycogenolysis, and glucose disappearance were measured before and during a hyperinsulinemic clamp using [6,6-(2)H2]glucose and the deuterated water method corrected for transaldolase exchange.<bold>Setting: </bold>The study was conducted at the Mayo Clinic Clinical Research Unit.<bold>Participants: </bold>Subjects with impaired fasting glucose (IFG)/normal glucose tolerance (NGT) (n = 14), IFG/impaired glucose tolerance (IGT) (n = 18), and normal fasting glucose (NFG)/NGT (n = 16) were studied.<bold>Intervention: </bold>A hyperinsulinemic clamp was used.<bold>Outcome Measures: </bold>Glucose production, glucose disappearance, gluconeogenesis, and glycogenolysis were measured.<bold>Results: </bold>Fasting glucose production was higher (P < .0001) in subjects with IFG/NGT than in those with NFG/NGT because of increased rates of gluconeogenesis (P = .003). On the other hand, insulin-induced suppression of glucose production, gluconeogenesis, glycogenolysis, and stimulation of glucose disappearance all were normal. Although fasting glucose production also was increased (P = .0002) in subjects with IFG/IGT, insulin-induced suppression of glucose production, gluconeogenesis, and glycogenolysis and stimulation of glucose disappearance were impaired (P = .005).<bold>Conclusions: </bold>Fasting hyperglycemia is due to excessive glucose production in people with either IFG/NGT or IFG/IGT. Both insulin action and postprandial glucose concentrations are normal in IFG/NGT but abnormal in IFG/IGT. This finding suggests that hepatic and extrahepatic insulin resistance causes or exacerbates postprandial glucose intolerance in IFG/IGT. Elevated gluconeogenesis in the fasting state in IFG/NGT and impaired insulin-induced suppression of both gluconeogenesis and glycogenolysis in IFG/IGT suggest that alteration in the regulation of these pathways occurs early in the evolution of type 2 diabetes.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2013, Vol 98, Issue 3, pE409
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2012-3056