Diabetes, Vol 38, Issue 3 291-303, Copyright © 1989 by American Diabetes Association

ARTICLES

Effects of basal insulin supplementation on disposition of mixed meal in obese patients with NIDDM

M McMahon, HM Marsh and RA Rizza
Department of Medicine, Mayo Clinic and Foundation, Rochester, MN 55905.

Basal insulin supplementation has been used as a therapy for patients with non-insulin-dependent diabetes mellitus (NIDDM) who require insulin. To determine whether basal insulin supplementation in addition to lowering postabsorptive plasma glucose concentration also improves the postprandial pattern of glucose disposition, glucose metabolism after ingestion of a solid mixed meal was assessed in obese patients with NIDDM before and after treatment with ultralente and compared with glucose metabolism observed in nondiabetic subjects. Splanchnic uptake of ingested glucose clearance was assessed by including [2-3H]glucose (a tracer that only minimally cycles through glycogen) in a solid mixed meal. Postprandial gluconeogenesis was estimated by measuring the rate of incorporation of carbon dioxide into glucose. Net glucose and lipid oxidation were measured by indirect calorimetry. Both splanchnic uptake of ingested glucose (27 +/- 1 vs. 14 +/- 2 g) and postprandial hepatic glucose release (51 +/- 5 vs. 24 +/- 3 g) were greater (P less than .001) in diabetic than in nondiabetic subjects. Although the percentage of postprandial hepatic glucose release accounted for by glucose synthesis from bicarbonate was similar in the two groups (25 +/- 2 vs. 35 +/- 5%), the absolute rate was greater in the diabetic patients (13 +/- 1 vs. 8 +/- 1 g; P less than .05). Postprandial glucose oxidation and glucose disposal (measured either isotopically or by the forearm-catheterization technique) were similar in both groups. However, total lipid oxidation was increased in the diabetic patients. (P less than .05). Two weeks of basal insulin supplementation lowered fasting glucose concentrations (from 219 +/- 22 to 144 +/- 21 mg/dl; P less than .01) and integrated postprandial glycemic response (from 814 +/- 68 to 621 +/- 72 min.mg.ml-1) but not to normal. Although circulating insulin concentrations were two- to threefold greater (P less than .02) after 3 mo of basal insulin supplementation, the postprandial pattern of glucose metabolism remained essentially the same. Basal insulin supplementation decreased (P less than .05) both splanchnic uptake of ingested glucose and hepatic glucose release. The addition of a preprandial injection of soluble insulin to basal insulin supplementation further suppressed (P less than .05) postprandial hepatic glucose release, thereby further improving postprandial glucose tolerance. These studies indicate that initial splanchnic glucose clearance, hepatic glucose release, and new glucose synthesis, as well as extrahepatic substrate metabolism, are altered in NIDDM after ingestion of a mixed meal.(ABSTRACT TRUNCATED AT 400 WORDS)
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Cervera, E. Wajcberg, A. Sriwijitkamol, M. Fernandez, P. Zuo, C. Triplitt, N. Musi, R. A. DeFronzo, and E. Cersosimo Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2 diabetes Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E846 - E852. [Abstract] [Full Text] [PDF]

				H. J. Woerle, E. Szoke, C. Meyer, J. M. Dostou, S. D. Wittlin, N. R. Gosmanov, S. L. Welle, and J. E. Gerich Mechanisms for abnormal postprandial glucose metabolism in type 2 diabetes Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E67 - E77. [Abstract] [Full Text] [PDF]

				M. Krssak, A. Brehm, E. Bernroider, C. Anderwald, P. Nowotny, C. D. Man, C. Cobelli, G. W. Cline, G. I. Shulman, W. Waldhausl, et al. Alterations in Postprandial Hepatic Glycogen Metabolism in Type 2 Diabetes Diabetes, December 1, 2004; 53(12): 3048 - 3056. [Abstract] [Full Text] [PDF]

				C. Meyer, H. J. Woerle, J. M. Dostou, S. L. Welle, and J. E. Gerich Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in type 2 diabetes Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1049 - E1056. [Abstract] [Full Text] [PDF]

				C. S. Stump, K. R. Short, M. L. Bigelow, J. M. Schimke, and K. S. Nair Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts PNAS, June 24, 2003; 100(13): 7996 - 8001. [Abstract] [Full Text] [PDF]

				H. J. Woerle, C. Meyer, J. M. Dostou, N. R. Gosmanov, N. Islam, E. Popa, S. D. Wittlin, S. L. Welle, and J. E. Gerich Pathways for glucose disposal after meal ingestion in humans Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E716 - E725. [Abstract] [Full Text] [PDF]

				R. K. Krishnan, W. J. Evans, and J. P. Kirwan Impaired substrate oxidation in healthy elderly men after eccentric exercise J Appl Physiol, February 1, 2003; 94(2): 716 - 723. [Abstract] [Full Text] [PDF]

				M. Bajaj, T. Pratipanawatr, R. Berria, W. Pratipanawatr, S. Kashyap, K. Cusi, L. Mandarino, and R. A. DeFronzo Free Fatty Acids Reduce Splanchnic and Peripheral Glucose Uptake in Patients With Type 2 Diabetes Diabetes, October 1, 2002; 51(10): 3043 - 3048. [Abstract] [Full Text] [PDF]

				C. Meyer, J. M. Dostou, S. L. Welle, and J. E. Gerich Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis Am J Physiol Endocrinol Metab, February 1, 2002; 282(2): E419 - E427. [Abstract] [Full Text] [PDF]

				M. C. Gannon, J. A. Nuttall, G. Damberg, V. Gupta, and F. Q. Nuttall Effect of Protein Ingestion on the Glucose Appearance Rate in People with Type 2 Diabetes J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1040 - 1047. [Abstract] [Full Text]

				J. D. Gresham, K. Okamura, P. E. Williams, K. Jabbour, and P. J. Flakoll Gastrointestinal tract, hepatic, hindlimb, and renal recovery of CO2 in vivo J Appl Physiol, November 1, 2000; 89(5): 2000 - 2006. [Abstract] [Full Text] [PDF]

				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]

				P. Iozzo, H. Beck-Nielsen, M. Laakso, U. Smith, H. Yki-Järvinen, and E. Ferrannini Independent Influence of Age on Basal Insulin Secretion in Nondiabetic Humans J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 863 - 868. [Abstract] [Full Text]

				S. D. Wise, M. F. Nielsen, P. E. Cryer, and R. A. Rizza Overnight Normalization of Glucose Concentrations Improves Hepatic But Not Extrahepatic Insulin Action in Subjects with Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2461 - 2469. [Abstract] [Full Text]

				S. Wise, M. Nielsen, and R. Rizza Effects of Hepatic Glycogen Content on Hepatic Insulin Action in Humans: Alteration in the Relative Contributions of Glycogenolysis and Gluconeogenesis to Endogenous Glucose Production J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1828 - 1833. [Abstract] [Full Text] [PDF]

				J. A. Colwell The Feasibility of Intensive Insulin Management in Non-Insulin-dependent Diabetes Mellitus: Implications of the Veterans Affairs Cooperative Study on Glycemic Control and Complications in NIDDM Ann Intern Med, January 1, 1996; 124(1_Part_2): 131 - 135. [Abstract] [Full Text]