Diabetes, Vol 45, Issue 7 947-953, Copyright © 1996 by American Diabetes Association

ARTICLES

Insulin action and age. European Group for the Study of Insulin Resistance (EGIR)

E Ferrannini, S Vichi, H Beck-Nielsen, M Laakso, G Paolisso and U Smith
University of Odense, Denmark.

Evidence that age is associated with insulin resistance is discordant. We analyzed euglycemic insulin clamp (1 mU x min(-1) x kg(-1)) data collected at 20 centers throughout Europe from 1,146 men and women with normal glucose tolerance, ranging in age from 18 to 85 years. In the whole group, insulin action (as the M value) declined slightly with age (at a rate of 0.9 micromol x min(-1)-kg(-1) per decade of life, 95% CI = 0.4-1.3, P = 0.0002). When adjusted for BMI, this relationship was no longer statistically significant. The same result was obtained whether insulin action was expressed per kilogram of body weight or per kilogram of fat-free mass, expressed as the M:I ratio, or estimated from fasting plasma insulin concentrations. Subgroup analysis showed that a significant BMI-adjusted decrease in insulin action with age was present only in lean (BMI <25 kg/m2) women (a rate of 1.6 micromol x min(-1) x kg(-1) per decade, 95% CI = 0.6-2.5, P = 0.001), in whom percentage fat mass also increased with age (by 0.38% body weight per decade, P = 0.0007). Insulin action was positively associated with insulin suppression of circulating free fatty acids (FFAs) (+1.5 micromol x min(-1) x kg(-1) for each 10% increase in FFA suppression, P < 0.0001) in a multivariate model accounting for sex, BMI, age, and fasting FFA levels. Furthermore, insulin suppression of FFAs improved with age in men (2% per decade, P < 0.0001) but not in women. In the subgroup of lean women in whom insulin action declined with age, adding FFA suppression to a multiple regression equation canceled the association between age and insulin action. Thus, the small effect of age on insulin action could be adequately explained on the basis of age-related changes in body composition and substrate competition. We conclude that in healthy Europeans, age per se is not a significant cause of insulin resistance of glucose metabolism or lipolysis.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C.-N. Chen, L.-M. Chuang, and Y.-T. Wu Clinical Measures of Physical Fitness Predict Insulin Resistance in People at Risk for Diabetes Physical Therapy, November 1, 2008; 88(11): 1355 - 1364. [Abstract] [Full Text] [PDF]

				C. A Conover, M. A Mason, J. A Levine, and C. M Novak Metabolic consequences of pregnancy-associated plasma protein-A deficiency in mice: exploring possible relationship to the longevity phenotype J. Endocrinol., September 1, 2008; 198(3): 599 - 605. [Abstract] [Full Text] [PDF]

				J. J. Dube, F. Amati, M. Stefanovic-Racic, F. G. S. Toledo, S. E. Sauers, and B. H. Goodpaster Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E882 - E888. [Abstract] [Full Text] [PDF]

				F. Escriva, M L. Gavete, Y. Fermin, C. Perez, N. Gallardo, C. Alvarez, A. Andres, M. Ros, and J. M Carrascosa Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: role of adiposity J. Endocrinol., July 1, 2007; 194(1): 131 - 141. [Abstract] [Full Text] [PDF]

				S. Gavi, L. M. Stuart, P. Kelly, M. M. Melendez, D. C. Mynarcik, M. C. Gelato, and M. A. McNurlan Retinol-Binding Protein 4 Is Associated with Insulin Resistance and Body Fat Distribution in Nonobese Subjects without Type 2 Diabetes J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1886 - 1890. [Abstract] [Full Text] [PDF]

				D. H. St-Pierre, A. D. Karelis, L. Coderre, F. Malita, J. Fontaine, D. Mignault, M. Brochu, J.-P. Bastard, K. Cianflone, E. Doucet, et al. Association of Acylated and Nonacylated Ghrelin with Insulin Sensitivity in Overweight and Obese Postmenopausal Women J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 264 - 269. [Abstract] [Full Text] [PDF]

				The Diabetes Prevention Program Research Group [Pr The influence of age on the effects of lifestyle modification and metformin in prevention of diabetes. J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2006; 61(10): 1075 - 1081. [Abstract] [Full Text] [PDF]

				A. M. Chang, M. J. Smith, A. T. Galecki, C. J. Bloem, and J. B. Halter Impaired {beta}-Cell Function in Human Aging: Response to Nicotinic Acid-Induced Insulin Resistance J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3303 - 3309. [Abstract] [Full Text] [PDF]

				W. Zhou, Y. Gu, H. Li, and M. Luo Assessing 1-h plasma glucose and shape of the glucose curve during oral glucose tolerance test. Eur. J. Endocrinol., July 1, 2006; 155(1): 191 - 197. [Abstract] [Full Text] [PDF]

				R. Basu, C. Dalla Man, M. Campioni, A. Basu, G. Klee, G. Toffolo, C. Cobelli, and R. A. Rizza Effects of age and sex on postprandial glucose metabolism: differences in glucose turnover, insulin secretion, insulin action, and hepatic insulin extraction. Diabetes, July 1, 2006; 55(7): 2001 - 2014. [Abstract] [Full Text] [PDF]

				S. B. Roberts and I. Rosenberg Nutrition and Aging: Changes in the Regulation of Energy Metabolism With Aging Physiol Rev, April 1, 2006; 86(2): 651 - 667. [Abstract] [Full Text] [PDF]

				S. Chevalier, R. Gougeon, N. Choong, M. Lamarche, and J. A. Morais Influence of adiposity in the blunted whole-body protein anabolic response to insulin with aging. J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2006; 61(2): 156 - 164. [Abstract] [Full Text] [PDF]

				A. M. Abbatecola, L. Ferrucci, G. Ceda, C. R. Russo, F. Lauretani, S. Bandinelli, M. Barbieri, G. Valenti, and G. Paolisso Insulin Resistance and Muscle Strength in Older Persons J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2005; 60(10): 1278 - 1282. [Abstract] [Full Text] [PDF]

				K. A. Virtanen, P. Iozzo, K. Hallsten, R. Huupponen, R. Parkkola, T. Janatuinen, F. Lonnqvist, T. Viljanen, T. Ronnemaa, P. Lonnroth, et al. Increased Fat Mass Compensates for Insulin Resistance in Abdominal Obesity and Type 2 Diabetes: A Positron-Emitting Tomography Study Diabetes, September 1, 2005; 54(9): 2720 - 2726. [Abstract] [Full Text] [PDF]

				S. E. Stern, K. Williams, E. Ferrannini, R. A. DeFronzo, C. Bogardus, and M. P. Stern Identification of Individuals With Insulin Resistance Using Routine Clinical Measurements Diabetes, February 1, 2005; 54(2): 333 - 339. [Abstract] [Full Text] [PDF]

				A. M. Poynten, S. K. Gan, A. D. Kriketos, L. V. Campbell, and D. J. Chisholm Circulating Fatty Acids, Non-High Density Lipoprotein Cholesterol, and Insulin-Infused Fat Oxidation Acutely Influence Whole Body Insulin Sensitivity in Nondiabetic Men J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1035 - 1040. [Abstract] [Full Text] [PDF]

				M. Kanauchi, K. Kimura, Y. Akai, and Y. Saito Insulin resistance and pancreatic beta-cell function in patients with hypertensive kidney disease Nephrol. Dial. Transplant., August 1, 2004; 19(8): 2025 - 2029. [Abstract] [Full Text] [PDF]

				M. G. Cree, B. R. Newcomer, C. S. Katsanos, M. Sheffield-Moore, D. Chinkes, A. Aarsland, R. Urban, and R. R. Wolfe Intramuscular and Liver Triglycerides Are Increased in the Elderly J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3864 - 3871. [Abstract] [Full Text] [PDF]

				M. van der Valk, G. Allick, G. J. Weverling, J. A. Romijn, M. T. Ackermans, J. M. A. Lange, B. L. F. van Eck-Smit, C. van Kuijk, E. Endert, H. P. Sauerwein, et al. Markedly Diminished Lipolysis and Partial Restoration of Glucose Metabolism, without Changes in Fat Distribution after Extended Discontinuation of Protease Inhibitors in Severe Lipodystrophic Human Immunodeficient Virus-1-Infected Patients J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3554 - 3560. [Abstract] [Full Text] [PDF]

				A. D. Karelis, D. H. St-Pierre, F. Conus, R. Rabasa-Lhoret, and E. T. Poehlman Metabolic and Body Composition Factors in Subgroups of Obesity: What Do We Know? J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2569 - 2575. [Abstract] [Full Text] [PDF]

				M. Zamboni, E. Zoico, F. Fantin, M. P. Panourgia, V. Di Francesco, P. Tosoni, B. Solerte, R. Vettor, and O. Bosello Relation Between Leptin and the Metabolic Syndrome in Elderly Women J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2004; 59(4): M396 - M400. [Abstract] [Full Text] [PDF]

				R. Basu, E. Breda, A. L. Oberg, C. C. Powell, C. Dalla Man, A. Basu, J. L. Vittone, G. G. Klee, P. Arora, M. D. Jensen, et al. Mechanisms of the Age-Associated Deterioration in Glucose Tolerance: Contribution of Alterations in Insulin Secretion, Action, and Clearance Diabetes, July 1, 2003; 52(7): 1738 - 1748. [Abstract] [Full Text] [PDF]

				R. K. Krishnan, W. J. Evans, and J. P. Kirwan Glucose Clearance Is Delayed after Hyperglycemia in Healthy Elderly Men J. Nutr., July 1, 2003; 133(7): 2363 - 2366. [Abstract] [Full Text] [PDF]

				R. S. Legro Polycystic Ovary Syndrome and Cardiovascular Disease: A Premature Association? Endocr. Rev., June 1, 2003; 24(3): 302 - 312. [Abstract] [Full Text] [PDF]

				P. Imbeault, J. B. Prins, M. Stolic, A. W. Russell, T. O'Moore-Sullivan, J.-P. Despres, C. Bouchard, and A. Tremblay Aging Per Se Does Not Influence Glucose Homeostasis: In vivo and in vitro evidence Diabetes Care, February 1, 2003; 26(2): 480 - 484. [Abstract] [Full Text] [PDF]

				C. M. Clevenger, P. Parker Jones, H. Tanaka, D. R. Seals, and C. A. DeSouza Decline in insulin action with age in endurance-trained humans J Appl Physiol, December 1, 2002; 93(6): 2105 - 2111. [Abstract] [Full Text] [PDF]

				X. H. Ma, R. Muzumdar, X. M. Yang, I. Gabriely, R. Berger, and N. Barzilai Aging Is Associated With Resistance to Effects of Leptin on Fat Distribution and Insulin Action J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2002; 57(6): B225 - 231. [Abstract] [Full Text]

				M. Gaster, I. Petersen, K. Hojlund, P. Poulsen, and H. Beck-Nielsen The Diabetic Phenotype Is Conserved in Myotubes Established From Diabetic Subjects: Evidence for Primary Defects in Glucose Transport and Glycogen Synthase Activity Diabetes, April 1, 2002; 51(4): 921 - 927. [Abstract] [Full Text] [PDF]

				I. Gabriely, X. H. Ma, X. M. Yang, L. Rossetti, and N. Barzilai Leptin Resistance During Aging Is Independent of Fat Mass Diabetes, April 1, 2002; 51(4): 1016 - 1021. [Abstract] [Full Text] [PDF]

				D. B. Sacks, D. E. Bruns, D. E. Goldstein, N. K. Maclaren, J. M. McDonald, and M. Parrott Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus Clin. Chem., March 1, 2002; 48(3): 436 - 472. [Abstract] [Full Text] [PDF]

				A. Fritsche, A. Madaus, N. Stefan, O. Tschritter, E. Maerker, A. Teigeler, H. Haring, and M. Stumvoll Relationships Among Age, Proinsulin Conversion, and {beta}-Cell Function in Nondiabetic Humans Diabetes, February 1, 2002; 51(90001): S234 - 239. [Abstract] [Full Text] [PDF]

				E. M. McConnell, A. B. Atkinson, C. Ennis, D. R. Hadden, D. R. McCance, B. Sheridan, and P. M. Bell The Effects on Insulin Action in Adult Hypopituitarism of Recombinant Human GH Therapy Individually Titrated for Six Months J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5342 - 5347. [Abstract] [Full Text] [PDF]

				W. F. DeNino, A. Tchernof, I. J. Dionne, M. J. Toth, P. A. Ades, C. K. Sites, and E. T. Poehlman Contribution of Abdominal Adiposity to Age-Related Differences in Insulin Sensitivity and Plasma Lipids in Healthy Nonobese Women Diabetes Care, May 1, 2001; 24(5): 925 - 932. [Abstract] [Full Text]

				A. F. Muller, J. A. Janssen, L. J. Hofland, S. W. Lamberts, M. Bidlingmaier, C. J. Strasburger, and A. J. van der Lely Blockade of the Growth Hormone (GH) Receptor Unmasks Rapid GH-Releasing Peptide-6-Mediated Tissue-Specific Insulin Resistance J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 590 - 593. [Abstract] [Full Text]

				Y. Boirie, P. Gachon, N. Cordat, P. Ritz, and B. Beaufrère Differential Insulin Sensitivities of Glucose, Amino Acid, and Albumin Metabolism in Elderly Men and Women J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 638 - 644. [Abstract] [Full Text]

				M. Gaster, P. Poulsen, A. Handberg, H. D. Schroder, and H. Beck-Nielsen Direct evidence of fiber type-dependent GLUT-4 expression in human skeletal muscle Am J Physiol Endocrinol Metab, May 1, 2000; 278(5): E910 - E916. [Abstract] [Full Text] [PDF]

				B. M. Balletshofer, K. Rittig, M. D. Enderle, A. Volk, E. Maerker, S. Jacob, S. Matthaei, K. Rett, and H. U. Haring Endothelial Dysfunction Is Detectable in Young Normotensive First-Degree Relatives of Subjects With Type 2 Diabetes in Association With Insulin Resistance Circulation, April 18, 2000; 101(15): 1780 - 1784. [Abstract] [Full Text] [PDF]

				G. Gupta, L. She, X.-H. Ma, X.-M. Yang, M. Hu, J. A. Cases, P. Vuguin, L. Rossetti, and N. Barzilai Aging does not contribute to the decline in insulin action on storage of muscle glycogen in rats Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2000; 278(1): R111 - R117. [Abstract] [Full Text] [PDF]

				J. H. Cox, R. N. Cortright, G. L. Dohm, and J. A. Houmard Effect of aging on response to exercise training in humans: skeletal muscle GLUT-4 and insulin sensitivity J Appl Physiol, June 1, 1999; 86(6): 2019 - 2025. [Abstract] [Full Text] [PDF]

				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]

				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]

				R. S. Legro, D. Finegood, and A. Dunaif A Fasting Glucose to Insulin Ratio Is a Useful Measure of Insulin Sensitivity in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2694 - 2698. [Abstract] [Full Text]

				G. Paolisso, M. R. Rizzo, G. Mazziotti, M. R. Tagliamonte, A. Gambardella, M. Rotondi, C. Carella, D. Giugliano, M. Varricchio, and F. D'Onofrio Advancing age and insulin resistance: role of plasma tumor necrosis factor-alpha Am J Physiol Endocrinol Metab, August 1, 1998; 275(2): E294 - E299. [Abstract] [Full Text] [PDF]

				A. Natali, A. Q. Galvan, N. Pecori, G. Sanna, E. Toschi, and E. Ferrannini Vasodilation With Sodium Nitroprusside Does Not Improve Insulin Action in Essential Hypertension Hypertension, February 1, 1998; 31(2): 632 - 636. [Abstract] [Full Text] [PDF]

				A. J Krentz Fortnightly Review: Insulin resistance BMJ, November 30, 1996; 313(7069): 1385 - 1389. [Abstract] [Full Text]