HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Utzschneider, K. M. Articles by Kahn, S. E. Search for Related Content PubMed PubMed Citation Articles by Utzschneider, K. M. Articles by Kahn, S. E. Social Bookmarking                What's this?

Impact of Differences in Fasting Glucose and Glucose Tolerance on the Hyperbolic Relationship Between Insulin Sensitivity and Insulin Responses

¹ Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and Harborview Medical Center, University of Washington, Seattle, Washington
² Geriatric Research, Education and Clinical Center, Baltimore VA Medical Center and Division of Gerontology, University of Maryland School of Medicine, Baltimore, Maryland
³ Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Washington, Seattle, Washington
⁴ Rehabilitation, Research and Development Center, VA Puget Sound Health Care System, Seattle, Washington

Address correspondence and reprint requests to Kristina M. Utzschneider, MD, VA Puget Sound Health Care System (151), 1660 S. Columbian Way, Seattle, WA 98108. E-mail: kutzschn{at}u.washington.edu

OBJECTIVE—To determine whether the hyperbolic relationship between insulin sensitivity and the acute insulin response to glucose (AIR_g) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance.

RESEARCH DESIGN AND METHODS—We studied 219 healthy subjects (88 male and 131 female subjects, aged 26–75 years) with fasting plasma glucose (FPG) <6.11 mmol/l. Subjects underwent an intravenous glucose tolerance test to determine the insulin sensitivity index (S_i), AIR_g, and the glucose disappearance constant (K_g), the latter a measure of intravenous glucose tolerance.

RESULTS—S_i and AIR_g were inversely related for the entire cohort, and this relationship was not significantly different from hyperbolic. The inverse relationship between S_i and AIR_g was not significantly different when compared between groups based on fasting glucose (normal fasting glucose [NFG], FPG <5.56 mmol/l vs. IFG, FPG 5.56–6.11 mmol/l) or by the K_g quartile. However, the curve relating S_i and AIR_g was left shifted in the IFG compared with NFG group (P < 0.001) and was progressively more left shifted with decreasing K_g (P < 0.001), consistent with decreasing ß-cell function. These changes were not observed for the curves relating S_i and fasting insulin, suggesting that in the fasting state ß-cell function is maintained even in patients with mild IFG. Finally, the disposition index (DI) (S_i x AIR_g) was calculated as a measure of ß-cell function. The DI progressively decreased with increasing FPG, even in the group of subjects classified as NFG.

CONCLUSIONS—The inverse relationship between insulin sensitivity and AIR_g is consistent with a hyperbola not only in subjects with normal glucose tolerance but also with mild IFG or decreased K_g. Based on a hyperbolic relationship, a decrease in ß-cell function can be detected as FPG increases, even in patients who are normal glucose tolerant.

Abbreviations: AIR_g, acute insulin response to glucose • DI, disposition index • FPG, fasting plasma glucose • IFG, impaired fasting glucose • NFG, normal fasting glucose

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

This article has been cited by other articles:

				A. I. Tarasov, T. J. Nicolson, J.-P. Riveline, T. K. Taneja, S. A. Baldwin, J. M. Baldwin, G. Charpentier, J.-F. Gautier, P. Froguel, M. Vaxillaire, et al. A Rare Mutation in ABCC8/SUR1 Leading to Altered ATP-Sensitive K+ Channel Activity and {beta}-Cell Glucose Sensing Is Associated With Type 2 Diabetes in Adults Diabetes, June 1, 2008; 57(6): 1595 - 1604. [Abstract] [Full Text] [PDF]

				K. M. Utzschneider, J. Tong, B. Montgomery, J. Udayasankar, F. Gerchman, S. M. Marcovina, C. E. Watson, M. A. Ligueros-Saylan, J. E. Foley, J. J. Holst, et al. The Dipeptidyl Peptidase-4 Inhibitor Vildagliptin Improves -Cell Function and Insulin Sensitivity in Subjects With Impaired Fasting Glucose Diabetes Care, January 1, 2008; 31(1): 108 - 113. [Abstract] [Full Text] [PDF]

				N. Rasouli, H. J. Spencer, A. A. Rashidi, and S. C. Elbein Impact of Family History of Diabetes and Ethnicity on -Cell Function in Obese, Glucose-Tolerant Individuals J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4656 - 4663. [Abstract] [Full Text] [PDF]

				M. F. Crutchlow, B. Robinson, B. Pappachen, N. Wimmer, A. J. Cucchiara, D. Cohen, and R. Townsend Validation of Steady-State Insulin Sensitivity Indices in Chronic Kidney Disease Diabetes Care, July 1, 2007; 30(7): 1813 - 1818. [Abstract] [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]

				S. Sakaue, S. Ishimaru, D. Ikeda, Y. Ohtsuka, T. Honda, J.-i. Suzuki, Y. Kawakami, J. Ishii, and M. Nishimura Estimation of beta-cell function from the data of the oral glucose tolerance test Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1575 - E1580. [Abstract] [Full Text] [PDF]

				G. Bock, C. Dalla Man, M. Campioni, E. Chittilapilly, R. Basu, G. Toffolo, C. Cobelli, and R. Rizza Effects of Nonglucose Nutrients on Insulin Secretion and Action in People With Pre-Diabetes Diabetes, April 1, 2007; 56(4): 1113 - 1119. [Abstract] [Full Text] [PDF]

				M. Cnop, J. Vidal, R. L. Hull, K. M. Utzschneider, D. B. Carr, T. Schraw, P. E. Scherer, E. J. Boyko, W. Y. Fujimoto, and S. E. Kahn Progressive Loss of {beta}-Cell Function Leads to Worsening Glucose Tolerance in First-Degree Relatives of Subjects With Type 2 Diabetes Diabetes Care, March 1, 2007; 30(3): 677 - 682. [Abstract] [Full Text] [PDF]

				N. Rasouli, P. A Kern, E. A. Reece, and S. C. Elbein Effects of pioglitazone and metformin on beta-cell function in nondiabetic subjects at high risk for type 2 diabetes Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E359 - E365. [Abstract] [Full Text] [PDF]

				G. Bock, C. Dalla Man, M. Campioni, E. Chittilapilly, R. Basu, G. Toffolo, C. Cobelli, and R. Rizza Pathogenesis of Pre-Diabetes: Mechanisms of Fasting and Postprandial Hyperglycemia in People With Impaired Fasting Glucose and/or Impaired Glucose Tolerance Diabetes, December 1, 2006; 55(12): 3536 - 3549. [Abstract] [Full Text] [PDF]