Glycemic Control Determines Hepatic and Peripheral Glucose Effectiveness in Type 2 Diabetic Subjects

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. 7; pp. 2179 - 2189
• Main Authors: HAWKINS, Meredith, GABRIELY, Ilan, WOZNIAK, Robert, REDDY, Kalpana, ROSSETTI, Luciano, SHAMOON, Harry
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2002
• Subjects: Abnormalities; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Mass Index; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty Acids, Nonesterified - blood; Glucagon - blood; Glucose; Glucose Clamp Technique; Glucose metabolism; Glycated Hemoglobin A - metabolism; Glycerol - blood; Humans; Hyperglycemia; Hyperglycemia - blood; Hyperglycemia - metabolism; Hyperlipidemia; Infusions, Intravenous; Insulin; Insulin - administration & dosage; Insulin - blood; Insulin - pharmacology; Kinases; Lactates - blood; Liver - metabolism; Medical sciences; Metabolism; Middle Aged; Phosphatase; Physiological aspects; Plasma; Reference Values; Somatostatin - blood; Type 2 diabetes; United States; Endocrinopathy; Human; Hyperglycemia; Glucose; Non insulin dependent diabetes
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.7.2179

Glycemic Control Determines Hepatic and Peripheral Glucose Effectiveness in Type 2 Diabetic Subjects Meredith Hawkins , Ilan Gabriely , Robert Wozniak , Kalpana Reddy , Luciano Rossetti and Harry Shamoon Division of Endocrinology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York 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 (∼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. Footnotes Address correspondence and reprint requests to Meredith Hawkins, Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. E-mail: hawkins{at}aecom.yu.edu . Received for publication 18 June 2001 and accepted in revised form 15 March 2002. AMPK, cAMP-dependent protein kinase; FFA, free fatty acid; G-6-Pase, glucose-6-phosphatase; GC, good control; GCRC, General Clinical Research Center; GK, glucokinase; GP, glucose production; ND, nondiabetic; PC, poor control; PC3day, PC subjects participating in the 3-day treatment. DIABETES