title: Impaired basal glucose effectiveness in NIDDM: contribution of defects in glucose disappearance and production, measured using an optimized minimal model independent protocol.
abstract: People with NIDDM are resistant to insulin. The present studies sought to determine whether the ability of glucose to regulate its own metabolism in the presence of basal insulin concentrations is impaired. To address this question, basal insulin concentrations were maintained constant with an exogenous insulin infusion, while endogenous hormone secretion was inhibited by somatostatin. The integrated glycemic response above baseline during identical prandial glucose infusions was greater (1,411 +/- 94 vs. 938 +/- 45 mmol/l per 5 h; P < 0.01) in the diabetic subjects than in the nondiabetic subjects, indicating a decrease in net glucose effectiveness. [6-3H]glucose also was infused to determine whether the decrease in net glucose effectiveness was due to a decrease in the ability of glucose to stimulate its own uptake and/or to suppress its own production. Despite identical rates of tracer infusion, the increment in plasma concentration of [6-3H]glucose was higher (4.50 +/- 0.29 vs. 3.16 +/- 0.21 x 10(5) dpm/ml per 5 h; P < 0.05) in the diabetic subjects than in the nondiabetic subjects. This was due to both a decrease (P < 0.05) in the ability of glucose to stimulate its own disappearance via mass action and to a greater (P < 0.01) inhibitory effect of glucose on its own clearance. The increase in glucose concentration resulted in prompt and comparable suppression of endogenous glucose production in both groups. Under these optimized conditions, indexes of glucose effectiveness calculated with both the "cold" and "hot" minimal models also were lower (P < 0.05) in the diabetic subjects than in the nondiabetic subjects and were highly correlated (r = 0.94-0.99; P < 0.001) with the indexes of glucose effectiveness calculated from the increments above baseline of glucose and [6-3H]glucose concentration. We conclude that the ability of glucose to regulate its own metabolism in the presence of basal insulin concentrations is abnormal in people with NIDDM.
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: A
authors.initials: A
authors.lastname: Basu
authors.forename: A
authors.initials: A
authors.lastname: Caumo
authors.forename: F
authors.initials: F
authors.lastname: Bettini
authors.forename: A
authors.initials: A
authors.lastname: Gelisio
authors.forename: A
authors.initials: A
authors.lastname: Alzaid
authors.forename: C
authors.initials: C
authors.lastname: Cobelli
authors.forename: R A
authors.initials: RA
authors.lastname: Rizza
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D008954:Models, Biological; D012016:Reference Values; D013004:Somatostatin / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019382:Human Growth Hormone; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose