Journal of Clinical Endocrinology & Metabolism, Vol 73, 866-876, Copyright © 1991 by Endocrine Society

ARTICLES

Exaggerated early insulin release and insulin resistance in a diabetes- prone population: a metabolic comparison of Pima Indians and Caucasians

S Lillioja, BL Nyomba, MF Saad, R Ferraro, C Castillo, PH Bennett and C Bogardus
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix Indian Medical Center/National Institutes of Health, Arizona 85016.

Pima Indians have the highest reported prevalence rate of noninsulin- dependent diabetes mellitus (NIDDM) in the world, so that metabolic comparisons with caucasians, who have a much lower rate, should provide insights into the pathogenesis of NIDDM. We have compared 81 caucasians with 211 Pima Indian nondiabetic subjects similar in age, sex, degree of obesity, and glucose tolerance. During a hyperinsulinemic euglycemic clamp at physiological insulin concentrations, Pima Indians were 17% more insulin resistant than caucasians after accounting for any differences in degree of obesity (P less than 0.0001). During oral glucose tolerance testing, mean plasma insulin concentrations were 33% higher in the Pimas (P less than 0.0001), but these differences were largely explained by the greater insulin resistance in the Pimas. Insulin clearance did not differ between the races. However, early insulin responses were exaggerated in the Indians and not explained by insulin resistance. After accounting for differences in insulin action, plasma insulin concentrations in Pima Indians were 50% higher than those in caucasians 3-5 min after iv glucose (P less than 0.0001), 38% higher 10 min after the end of a meal (P less than 0.0001), and 20% higher 30 min after an oral glucose load (P less than 0.006). These data suggest that in addition to insulin resistance, Pima Indians have exaggerated early insulin release and either increased beta-cell mass or enhanced beta-cell sensitivity to glucose. The data argue against low or delayed insulin secretion as primary factors leading to NIDDM in Pima Indians and favor insulin resistance as the underlying and initiating cause of the disease.

This article has been cited by other articles:

				J. Vrbikova, M. Hill, B. Bendlova, T. Grimmichova, K. Dvorakova, K. Vondra, and G. Pacini Incretin levels in polycystic ovary syndrome Eur. J. Endocrinol., August 1, 2008; 159(2): 121 - 127. [Abstract] [Full Text] [PDF]

				J. Koska, E. Ortega, C. Bogardus, J. Krakoff, and J. C. Bunt The effect of insulin on net lipid oxidation predicts worsening of insulin resistance and development of type 2 diabetes mellitus Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E264 - E269. [Abstract] [Full Text] [PDF]

				M. A. Abdul-Ghani, D. Tripathy, and R. A. DeFronzo Contributions of {beta}-Cell Dysfunction and Insulin Resistance to the Pathogenesis of Impaired Glucose Tolerance and Impaired Fasting Glucose Diabetes Care, May 1, 2006; 29(5): 1130 - 1139. [Abstract] [Full Text] [PDF]

				T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [Abstract] [Full Text] [PDF]

				B. V. de Courten, C. Weyer, N. Stefan, M. Horton, A. DelParigi, P. Havel, C. Bogardus, and P. A. Tataranni Parasympathetic Blockade Attenuates Augmented Pancreatic Polypeptide But Not Insulin Secretion in Pima Indians Diabetes, March 1, 2004; 53(3): 663 - 671. [Abstract] [Full Text] [PDF]

				M. L. Cruz, R. N. Bergman, and M. I. Goran Unique Effect of Visceral Fat on Insulin Sensitivity in Obese Hispanic Children With a Family History of Type 2 Diabetes Diabetes Care, September 1, 2002; 25(9): 1631 - 1636. [Abstract] [Full Text] [PDF]

				S. Dickinson, S. Colagiuri, E. Faramus, P. Petocz, and J. C. Brand-Miller Postprandial Hyperglycemia and Insulin Sensitivity Differ among Lean Young Adults of Different Ethnicities J. Nutr., September 1, 2002; 132(9): 2574 - 2579. [Abstract] [Full Text] [PDF]

				J. Vrbikova, B. Bendlova, M. Hill, M. Vankova, K. Vondra, and L. Starka Insulin Sensitivity and {beta}-Cell Function in Women With Polycystic Ovary Syndrome Diabetes Care, July 1, 2002; 25(7): 1217 - 1222. [Abstract] [Full Text] [PDF]

				A. Verrotti, F. Basciani, M. De Simone, D. Trotta, G. Morgese, and F. Chiarelli Insulin Resistance in Epileptic Girls Who Gain Weight After Therapy With Valproic Acid J Child Neurol, April 1, 2002; 17(4): 265 - 268. [Abstract] [PDF]

				C. Weyer, T. Funahashi, S. Tanaka, K. Hotta, Y. Matsuzawa, R. E. Pratley, and P. A. Tataranni Hypoadiponectinemia in Obesity and Type 2 Diabetes: Close Association with Insulin Resistance and Hyperinsulinemia J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1930 - 1935. [Abstract] [Full Text]

				P. Iozzo, T. Pratipanawatr, H. Pijl, C. Vogt, V. Kumar, R. Pipek, M. Matsuda, L. J. Mandarino, K. J. Cusi, and R. A. DeFronzo Physiological hyperinsulinemia impairs insulin-stimulated glycogen synthase activity and glycogen synthesis Am J Physiol Endocrinol Metab, May 1, 2001; 280(5): E712 - E719. [Abstract] [Full Text] [PDF]

				M. Freemark and D. Bursey The Effects of Metformin on Body Mass Index and Glucose Tolerance in Obese Adolescents With Fasting Hyperinsulinemia and a Family History of Type 2 Diabetes Pediatrics, April 1, 2001; 107(4): e55 - e55. [Abstract] [Full Text] [PDF]

				T. A. Buchanan Pancreatic B-Cell Defects in Gestational Diabetes: Implications for the Pathogenesis and Prevention of Type 2 Diabetes J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 989 - 993. [Full Text]

				C. Weyer, R. E. Pratley, S. Snitker, M. Spraul, E. Ravussin, and P. A. Tataranni Ethnic Differences in Insulinemia and Sympathetic Tone as Links Between Obesity and Blood Pressure Hypertension, October 1, 2000; 36(4): 531 - 537. [Abstract] [Full Text] [PDF]

				J. F. Martin, C. S. Johnston, C.-T. Han, and D. C. Benyshek Nutritional Origins of Insulin Resistance: A Rat Model for Diabetes-Prone Human Populations J. Nutr., April 1, 2000; 130(4): 741 - 744. [Abstract] [Full Text]

				E. Ferrannini Insulin Resistance versus Insulin Deficiency in Non-Insulin-Dependent Diabetes Mellitus: Problems and Prospects Endocr. Rev., August 1, 1998; 19(4): 477 - 490. [Abstract] [Full Text] [PDF]

				S. J. Koopmans, L. Mandarino, and R. A. Defronzo Time course of insulin action on tissue-specific intracellular glucose metabolism in normal rats Am J Physiol Endocrinol Metab, April 1, 1998; 274(4): E642 - E650. [Abstract] [Full Text] [PDF]

				S. Arslanian Insulin Secretion and Sensitivity in Healthy African-American vs American White Children Clinical Pediatrics, February 1, 1998; 37(2): 81 - 88. [Abstract] [PDF]

				N. I. Teufel and C. K. Ritenbaugh Development of a Primary Prevention Program: Insight Gained in the Zuni Diabetes Prevention Program Clinical Pediatrics, February 1, 1998; 37(2): 131 - 141. [Abstract] [PDF]

				S. Arslanian, C. Suprasongsin, and J. E. Janosky Insulin Secretion and Sensitivity in Black Versus White Prepubertal Healthy Children J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1923 - 1927. [Abstract] [Full Text] [PDF]

				S. Lillioja, D. M. Mott, M. Spraul, R. Ferraro, J. E. Foley, E. Ravussin, W. C. Knowler, P. H. Bennett, and C. Bogardus Insulin Resistance and Insulin Secretory Dysfunction as Precursors of Non-Insulin-Dependent Diabetes Mellitus: Prospective Studies of Pima Indians N. Engl. J. Med., December 30, 1993; 329(27): 1988 - 1992. [Abstract] [Full Text]