Pathogenesis of prediabetes

Role of the liver in isolated fasting hyperglycemia and combined fasting and postprandial hyperglycemia

Rita Basu, Cristina Barosa, John Jones, Simmi Dube, Rickey E. Carter, Ananda Basu, Robert A. Rizza

Research output: Contribution to journalArticle

43 Citations (Scopus)

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- 2H2]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.

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

Prediabetic State
Hyperglycemia
Liver
Fasting
Glucose
Glucose Intolerance
Gluconeogenesis
Glycogenolysis
Insulin

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Pathogenesis of prediabetes : Role of the liver in isolated fasting hyperglycemia and combined fasting and postprandial hyperglycemia. / Basu, Rita; Barosa, Cristina; Jones, John; Dube, Simmi; Carter, Rickey E.; Basu, Ananda; Rizza, Robert A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 3, 03.2013.

Research output: Contribution to journalArticle

@article{b8913fa2833b4c688d582731b85f5d2d,
title = "Pathogenesis of prediabetes: Role of the liver in isolated fasting hyperglycemia and combined fasting and postprandial hyperglycemia",
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- 2H2]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.",
author = "Rita Basu and Cristina Barosa and John Jones and Simmi Dube and Carter, {Rickey E.} and Ananda Basu and Rizza, {Robert A.}",
year = "2013",
month = "3",
doi = "10.1210/jc.2012-3056",
language = "English (US)",
volume = "98",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Pathogenesis of prediabetes

T2 - Role of the liver in isolated fasting hyperglycemia and combined fasting and postprandial hyperglycemia

AU - Basu, Rita

AU - Barosa, Cristina

AU - Jones, John

AU - Dube, Simmi

AU - Carter, Rickey E.

AU - Basu, Ananda

AU - Rizza, Robert A.

PY - 2013/3

Y1 - 2013/3

N2 - 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- 2H2]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.

AB - 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- 2H2]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.

UR - http://www.scopus.com/inward/record.url?scp=84874826222&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874826222&partnerID=8YFLogxK

U2 - 10.1210/jc.2012-3056

DO - 10.1210/jc.2012-3056

M3 - Article

VL - 98

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -