Fasting hyperglycemia in non-insulin-dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake.
The factors responsible for fasting hyperglycemia were investigated in 77 normal weight non-insulin-dependent diabetic (NIDD) and 72 age-, sex-, and weight-matched control individuals. In diabetic subjects with mild fasting hyperglycemia (less than 140 mg/dL) hepatic glucose production (1.85 +/- 0.03 mg/kg.min) was similar to controls (1.84 +/- 0.02); the major factor responsible for the elevated basal glucose level in the diabetic group was a decreased efficiency in the tissue uptake of glucose, as reflected by a 30% decline in the rate of glucose clearance (1.56 +/- 0.03 v 2.00 +/- 0.03 mL/kg.min, P less than .001). In contrast, in diabetic subjects with fasting plasma glucose concentrations above 140 mg/dL, basal hepatic glucose production was significantly elevated (2.42 +/- 0.08 mg/kg.min, P less than .001) and correlated closely with the increase in fasting plasma glucose concentration (r = .796, P less than .001). The basal rate of whole body glucose clearance reached a plateau value at fasting glucose levels of 160 to 180 mg/dL and did not contribute to the further rise in fasting plasma glucose concentrations above 160 to 180 mg/dL. Decreased efficiency of tissue glucose uptake is responsible the development of fasting hyperglycemia in patients with mild NIDDM (fasting plasma glucose less than 140 mg/dL). As the diabetic state worsens, an increase in basal hepatic glucose production is the major factor responsible for the progressive rise in fasting glucose levels.
DeFronzo
R A
RA
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Ferrannini
E
E
Simonson
D C
DC
D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism*; D005215:Fasting; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology* / Q000378:metabolism; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose