Diabetes, Vol 46, Issue 3 421-432, Copyright © 1997 by American Diabetes Association

ARTICLES

Impaired basal glucose effectiveness in NIDDM: contribution of defects in glucose disappearance and production, measured using an optimized minimal model independent protocol

A Basu, A Caumo, F Bettini, A Gelisio, A Alzaid, C Cobelli and RA Rizza
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.

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.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Basu, V. Chandramouli, B. Dicke, B. R. Landau, and R. A. Rizza Plasma C5 Glucose-to-2H2O Ratio Does Not Provide an Accurate Assessment of Gluconeogenesis During Hyperinsulinemic-Euglycemic Clamps in Either Nondiabetic or Diabetic Humans Diabetes, July 1, 2008; 57(7): 1800 - 1804. [Abstract] [Full Text] [PDF]

				R. N. Bergman Orchestration of Glucose Homeostasis: From a Small Acorn to the California Oak Diabetes, June 1, 2007; 56(6): 1489 - 1501. [Full Text] [PDF]

				G. Bock, E. Chittilapilly, R. Basu, G. Toffolo, C. Cobelli, V. Chandramouli, B. R. Landau, and R. A. Rizza Contribution of Hepatic and Extrahepatic Insulin Resistance to the Pathogenesis of Impaired Fasting Glucose: Role of Increased Rates of Gluconeogenesis Diabetes, June 1, 2007; 56(6): 1703 - 1711. [Abstract] [Full Text] [PDF]

				R. N.M. Weijers and D. J. Bekedam Relationship between Gestational Diabetes Mellitus and Type 2 Diabetes: Evidence of Mitochondrial Dysfunction Clin. Chem., March 1, 2007; 53(3): 377 - 383. [Abstract] [Full Text] [PDF]

				M. C. Riddle and D. J. Drucker Emerging Therapies Mimicking the Effects of Amylin and Glucagon-Like Peptide 1 Diabetes Care, February 1, 2006; 29(2): 435 - 449. [Full Text] [PDF]

				R. Basu, V. Chandramouli, B. Dicke, B. Landau, and R. Rizza Obesity and Type 2 Diabetes Impair Insulin-Induced Suppression of Glycogenolysis as Well as Gluconeogenesis Diabetes, July 1, 2005; 54(7): 1942 - 1948. [Abstract] [Full Text] [PDF]

				C. Bouche, S. Serdy, C. R. Kahn, and A. B. Goldfine The Cellular Fate of Glucose and Its Relevance in Type 2 Diabetes Endocr. Rev., October 1, 2004; 25(5): 807 - 830. [Abstract] [Full Text] [PDF]

				C. Dalla Man, A. Caumo, R. Basu, R. Rizza, G. Toffolo, and C. Cobelli Minimal model estimation of glucose absorption and insulin sensitivity from oral test: validation with a tracer method Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E637 - E643. [Abstract] [Full Text] [PDF]

				R. Basu, A. Basu, C. M. Johnson, W. F. Schwenk, and R. A. Rizza Insulin Dose-Response Curves for Stimulation of Splanchnic Glucose Uptake and Suppression of Endogenous Glucose Production Differ in Nondiabetic Humans and Are Abnormal in People With Type 2 Diabetes Diabetes, August 1, 2004; 53(8): 2042 - 2050. [Abstract] [Full Text] [PDF]

				R. Basu, W. F. Schwenk, and R. A. Rizza Both fasting glucose production and disappearance are abnormal in people with "mild" and "severe" type 2 diabetes Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E55 - E62. [Abstract] [Full Text] [PDF]

				M. F. Nielsen, A. Caumo, V. Chandramouli, W. C. Schumann, C. Cobelli, B. R. Landau, H. Vilstrup, R. A. Rizza, and O. Schmitz Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E102 - E110. [Abstract] [Full Text]

				A. Vella, A. S. Reed, N. Charkoudian, P. Shah, R. Basu, A. Basu, M. J. Joyner, and R. A. Rizza Glucose-induced suppression of endogenous glucose production: dynamic response to differing glucose profiles Am J Physiol Endocrinol Metab, July 1, 2003; 285(1): E25 - E30. [Abstract] [Full Text] [PDF]

				H. C. Murphy, G. Regan, I. G. Bogdarina, A. J.L. Clark, R. A. Iles, R. D. Cohen, G. A. Hitman, C. L. Berry, Z. Coade, C. J. Petry, et al. Fetal Programming of Perivenous Glucose Uptake Reveals a Regulatory Mechanism Governing Hepatic Glucose Output During Refeeding Diabetes, June 1, 2003; 52(6): 1326 - 1332. [Abstract] [Full Text] [PDF]

				G. Toffolo and C. Cobelli The hot IVGTT two-compartment minimal model: an improved version Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E317 - E321. [Abstract] [Full Text] [PDF]

				P. Singhal, A. Caumo, P. E. Carey, C. Cobelli, and R. Taylor Regulation of endogenous glucose production after a mixed meal in type 2 diabetes Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E275 - E283. [Abstract] [Full Text] [PDF]

				C. J. Greenbaum, R. L. Prigeon, and D. A. D'Alessio Impaired {beta}-Cell Function, Incretin Effect, and Glucagon Suppression in Patients With Type 1 Diabetes Who Have Normal Fasting Glucose Diabetes, April 1, 2002; 51(4): 951 - 957. [Abstract] [Full Text] [PDF]

				E. Breda, M. K. Cavaghan, G. Toffolo, K. S. Polonsky, and C. Cobelli Oral Glucose Tolerance Test Minimal Model Indexes of {beta}-Cell Function and Insulin Sensitivity Diabetes, January 1, 2001; 50(1): 150 - 158. [Abstract] [Full Text]

				P. Shah, A. Vella, A. Basu, R. Basu, W. F. Schwenk, and R. A. Rizza Lack of Suppression of Glucagon Contributes to Postprandial Hyperglycemia in Subjects with Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4053 - 4059. [Abstract] [Full Text]

				P. Shah, A. Basu, R. Basu, and R. Rizza Impact of lack of suppression of glucagon on glucose tolerance in humans Am J Physiol Endocrinol Metab, August 1, 1999; 277(2): E283 - E290. [Abstract] [Full Text] [PDF]

				R. Basu, A. Basu, M. Nielsen, P. Shah, and R. A. Rizza Effect of Overnight Restoration of Euglycemia on Glucose Effectiveness in Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2314 - 2319. [Abstract] [Full Text]

				A. Caumo, P. Vicini, J. J. Zachwieja, A. Avogaro, K. Yarasheski, D. M. Bier, and C. Cobelli Undermodeling affects minimal model indexes: insights from a two-compartment model Am J Physiol Endocrinol Metab, June 1, 1999; 276(6): E1171 - E1193. [Abstract] [Full Text] [PDF]

				C. Cobelli, F. Bettini, A. Caumo, and M. J. Quon Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling Am J Physiol Endocrinol Metab, December 1, 1998; 275(6): E1031 - E1036. [Abstract] [Full Text] [PDF]

				G. Pacini, G. Tonolo, M. Sambataro, M. Maioli, M. Ciccarese, E. Brocco, A. Avogaro, and R. Nosadini Insulin sensitivity and glucose effectiveness: minimal model analysis of regular and insulin-modified FSIGT Am J Physiol Endocrinol Metab, April 1, 1998; 274(4): E592 - E599. [Abstract] [Full Text] [PDF]

				A. Caumo, C. Cobelli;, and D. T. Finegood Letters to the Editor Am J Physiol Endocrinol Metab, March 1, 1998; 274(3): E573 - E576. [Abstract] [Full Text] [PDF]