Format

Send to

Choose Destination
J Clin Endocrinol Metab. 2013 Mar;98(3):E409-17. doi: 10.1210/jc.2012-3056. Epub 2013 Jan 23.

Pathogenesis of prediabetes: role of the liver in isolated fasting hyperglycemia and combined fasting and postprandial hyperglycemia.

Author information

1
Endocrine Research Unit, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo College of Medicine, 200 First Street, Southwest, Rochester, Minnesota 55905, USA. basu.rita@mayo.edu

Abstract

CONTEXT:

People with prediabetes are at high risk of developing diabetes.

OBJECTIVE:

The objective of this study was to determine the pathogenesis of fasting and postprandial hyperglycemia in prediabetes.

DESIGN:

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.

SETTING:

The study was conducted at the Mayo Clinic Clinical Research Unit.

PARTICIPANTS:

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.

INTERVENTION:

A hyperinsulinemic clamp was used.

OUTCOME MEASURES:

Glucose production, glucose disappearance, gluconeogenesis, and glycogenolysis were measured.

RESULTS:

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).

CONCLUSIONS:

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.

PMID:
23345093
PMCID:
PMC3590488
DOI:
10.1210/jc.2012-3056
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center