title: Glycemic control determines hepatic and peripheral glucose effectiveness in type 2 diabetic subjects.
abstract: Glucose effectiveness is impaired in type 2 diabetes. We hypothesize that chronic hyperglycemia and hyperlipidemia contribute importantly to this defect. To test this hypothesis, we compared the effect of acute hyperglycemia on glucose turnover in type 2 diabetic subjects in good control (GC) (n = 14, age 51.7 +/- 3.7 years, BMI 28.4 +/- 1.0 kg/ m(2), HbA(1c) 5.9 +/- 0.2%) and poor control (PC) (n = 10, age 50.0 +/- 2.5 years, BMI 27.9 +/- 1.5 kg/m(2), HbA(1c) 9.9 +/- 0.6%) with age- and weight-matched nondiabetic subjects (ND) (n = 11, age 47.0 +/- 4.4 years, BMI 28.5 +/- 1.0 kg/m(2), HbA(1c) 5.1 +/- 0.2%). Fixed hormonal conditions were attained by infusing somatostatin for 6 h with replacement of basal insulin, glucagon, and growth hormone. Glucose fluxes ([3-(3)H]glucose) were compared during euglycemic (5 mmol/l, t = 180-240 min) and hyperglycemic (Hy) (10 mmol/l, t = 300-360 min, variable glucose infusion) clamp intervals. Acute hyperglycemia suppressed hepatic glucose production (GP) by 43% and increased peripheral glucose uptake (GU) by 86% in the ND subjects. Conversely, GP failed to suppress (-7%) and GU was suboptimally increased (+34%) in response to Hy in the PC group. However, optimal glycemic control was associated with normal glucose effectiveness in GC subjects (GP -38%, GU +72%; P > 0.05 for GC vs. ND). To determine whether short-term correction of hyperglycemia and/or hyperlipidemia is sufficient to reverse the impairment in glucose effectiveness, five PC subjects were restudied after 72 h of normoglycemia ( approximately 100 mg/dl; variable insulin infusions). These subjects regained normal effectiveness of glucose to suppress GP and stimulate GU and in response to Hy (GP -47%, GU + 71%; P > 0.05 vs. baseline studies). Thus, chronic hyperglycemia and/or hyperlipidemia contribute to impaired effectiveness of glucose in regulating glucose fluxes in type 2 diabetes and hence to worsening of the overall metabolic condition. Short-term normalization of plasma glucose might break the vicious cycle of impaired glucose effectiveness in type 2 diabetes.
authors.affiliation: Division of Endocrinology and Diabetes Research and Training Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. hawkins@aecom.yu.edu
authors.forename: Meredith
authors.initials: M
authors.lastname: Hawkins
authors.forename: Ilan
authors.initials: I
authors.lastname: Gabriely
authors.forename: Robert
authors.initials: R
authors.lastname: Wozniak
authors.forename: Kalpana
authors.initials: K
authors.lastname: Reddy
authors.forename: Luciano
authors.initials: L
authors.lastname: Rossetti
authors.forename: Harry
authors.initials: H
authors.lastname: Shamoon
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism*; D005990:Glycerol / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007773:Lactates / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008875:Middle Aged; D012016:Reference Values; D013004:Somatostatin / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D006442:Glycated Hemoglobin; D005990:Glycerol; D007328:Insulin; D007773:Lactates; D013004:Somatostatin