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Insulin Resistance with Aging

Effects of Diet and Exercise

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Abstract

Insulin resistance, a reduction in the rate of glucose disposal elicited by a given insulin concentration, is present in individuals who are obese, and those with diabetes mellitus, and may develop with aging. Methods which are utilised to measure insulin sensitivity include the hyperinsulinaemic-euglycaemic and hyperglycaemic clamps and the intravenous glucose tolerance tests. Several hormones and regulatory factors affect insulin action and may contribute to the insulin resistance observed in obesity. In addition, abnormal free fatty acid metabolism plays an important role in insulin resistance and the abnormal carbohydrate metabolism seen in individuals who are obese or diabetic. Thus, the mechanisms underlying the development of insulin resistance are multifactorial, and also involve alterations of the insulin signalling pathway.

Aging is associated with an increase in bodyweight and fat mass. Not only is abdominal fat associated with hyperinsulinaemia but visceral adiposity is correlated with insulin resistance as well. Modifications of the changes in body composition with aging by diet and exercise training could delay the onset of insulin resistance. Weight loss and aerobic and resistive exercise training result in losses of total body fat and abdominal fat. Several studies report that bodyweight loss increases insulin sensitivity and improves glucose tolerance. In addition, the insulin resistance observed in aged persons can be modified by physical training. Longitudinal studies indicate significant improvements in glucose metabolism with aerobic exercise training in middle-aged and older men and women. Moreover, the improvements in insulin sensitivity with resistive training are similar in magnitude to those achieved with aerobic exercise. The improvements in glucose metabolism after bodyweight loss and exercise training may in some cases be partially attributed to changes in body composition, including reductions in total and central body fat. Yet, additional changes in skeletal muscle, blood flow and other mechanisms likely interact to modify insulin resistance with exercise training. Lifestyle modifications including bodyweight loss and physical activity provide health benefits and functional gains and should be promoted to increase insulin sensitivity and prevent glucose intolerance and type 2 diabetes mellitus in older adults.

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References

  1. Godsland IF, Stevenson JC. Insulin resistance: syndrome or tendency? Lancet 1995; 346: 100–3

    Article  PubMed  CAS  Google Scholar 

  2. Scheen AJ, Paquot N, Castillo MG, et al. How to measure insulin action in vivo. Diabetes Metab Rev 1994; 10: 151–88

    Article  PubMed  CAS  Google Scholar 

  3. Kahn CR. Insulin resistance, insulin insensitivity, and insulin unresponsiveness: a necessary distinction. Metabolism 1978; 27: 1893–902

    Article  PubMed  CAS  Google Scholar 

  4. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–607

    Article  PubMed  CAS  Google Scholar 

  5. Haffner SM, Miettinen H, Stern MP. Insulin secretion and resistance in nondiabetic Mexican Americans and Non-Hispanic Whites with a parental history of diabetes. J Clin Endocrinol Metab 1996; 81: 1846–51

    Article  PubMed  CAS  Google Scholar 

  6. Andres R, Swerdloff RS, Pozefsky T, et al. 1966 manual feedback technique for the control of blood glucose concentration. In: Skeggs LT, editor. Automation in analytical chemistry (technician symposium). New York (NY): Mediad, 1966: 489–91

    Google Scholar 

  7. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237 (3): E214–23

    PubMed  CAS  Google Scholar 

  8. Bergman RN, Finegood DT, Ader M. Assessment of insulin sensitivity in vivo. Endocrinol Rev 1985; 6: 45–86

    Article  CAS  Google Scholar 

  9. Bergman RN, Prager R, Volund A, et al. Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp. J Clin Invest 1987; 79: 790–800

    Article  PubMed  CAS  Google Scholar 

  10. Chalew SA, Zadik Z, Lozano RA, et al. Plasma cortisol levels increase with age in obese subjects. Obes Res 1993; 1: 199–202

    PubMed  CAS  Google Scholar 

  11. Marin P, Darin N, Amemiya T, et al. Cortisol secretion in relation to body fat distribution in obese premenopausal women. Metabolism 1992; 41: 882–6

    Article  PubMed  CAS  Google Scholar 

  12. Rizza RA, Mandarino LJ, Gerich JE. Cortisol-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action. J Clin Endocrinol Metab 1982; 54: 131–8

    Article  PubMed  CAS  Google Scholar 

  13. Lefebvre PJ. Glucagon and its family revisited. Diabetes Care 1995; 18: 715–30

    PubMed  CAS  Google Scholar 

  14. Rudman D, Kutner MH, Rogers CM, et al. Impaired growth hormone secretion in the adult population. J Clin Invest 1981; 67: 1361–9

    Article  PubMed  CAS  Google Scholar 

  15. Copeland KC, Colletti RB, Devlin JD, et al. The relationship between insulin-like growth factor-I, adiposity and aging. Metabolism 1990; 39: 584–7

    Article  PubMed  CAS  Google Scholar 

  16. Poehlman ET, Copeland KC. Influence of physical activity on insulin-like growth factor-I in healthy younger and older men. J Clin Endocrinol Metab 1990; 71: 1468–73

    Article  PubMed  CAS  Google Scholar 

  17. Kjaer M. Regulation of hormonal and metabolic responses during exercise in humans. In: Holloszy JO, editor. Exercise and sport sciences reviews. Vol. 20. Baltimore (MD): Williams and Wilkins, 1992: 161–84

    Google Scholar 

  18. Tataranni PA, Young JB, Bogardus C, et al. A low sympathoadrenal activity is associated with body weight gain and development of central adiposity in Pima Indian men. Obes Res 1997; 5: 341–7

    PubMed  CAS  Google Scholar 

  19. Virkamaki A, Ueki K, Kahn CR. Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance. J Clin Invest 1999; 103: 931–43

    Article  PubMed  CAS  Google Scholar 

  20. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–32

    Article  PubMed  CAS  Google Scholar 

  21. Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292–5

    Article  PubMed  CAS  Google Scholar 

  22. Considine RV, Considine EL, Williams CJ, et al. Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J Clin Invest 1995; 95: 2986–8

    Article  PubMed  CAS  Google Scholar 

  23. Ryan AS, Elahi D. The effects of acute hyperglycemia and hyperinsulinemia on plasma leptin levels: its relationships with body fat, visceral adiposity, and age in women. J Clin Endocrinol Metab 1996; 81: 4433–8

    Article  PubMed  CAS  Google Scholar 

  24. Siegel KR, Landt M, Klein S. Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes 1996; 45: 988–91

    Article  Google Scholar 

  25. Keiffer TL, Heller RS, Habener JF. Leptin receptors expressed on pancreatic β-cells. Biochem Biophys Res Commun 1996; 224: 522–7

    Article  Google Scholar 

  26. Kulkarni RN, Wang Z, Wang R, et al. Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice. J Clin Invest 1997; 100: 2729–36

    Article  PubMed  CAS  Google Scholar 

  27. Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269: 540–3

    Article  PubMed  CAS  Google Scholar 

  28. Hwa JJ, Fawzi AB, Graziano MP, et al. Leptin increases energy expenditure and selectively promotes fat metabolism in ob/ob mice. Am J Physiol 1997; 41: R1204–9

    Google Scholar 

  29. Wabitsch M, Jensen PB, Blum WF, et al. Insulin and cortisol promote leptin production in cultured human fat cells. Diabetes 1996; 45: 1435–8

    Article  PubMed  CAS  Google Scholar 

  30. Cohen B, Novick D, Rubinstein M. Modulation of insulin activities by leptin. Science 1996; 274: 1185–8

    Article  PubMed  CAS  Google Scholar 

  31. Kennedy A, Gettys TW, Watson P, et al. The metabolism significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure. J Clin Endocrinol Metab 1997; 82: 1293–300

    Article  PubMed  CAS  Google Scholar 

  32. Morley JE. An overview of diabetes mellitus in older persons. Clin Geriatr Med 1999; 15: 211–24

    PubMed  CAS  Google Scholar 

  33. Nicklas BJ, Katzel LI, Ryan AS, et al. Gender differences in the response of plasma leptin concentrations to weight loss in obese older individuals. Obes Res 1997; 5: 62–7

    PubMed  CAS  Google Scholar 

  34. Halaas JL, Gajiwala KS, Maffei M, et al. Weight reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 543–6

    Article  PubMed  CAS  Google Scholar 

  35. Perusse L, Collier G, Gagnon J, et al. Acute and chronic effects of exercise on leptin levels in humans. J Appl Physiol 1997; 83: 5–10

    PubMed  CAS  Google Scholar 

  36. Kohrt WM, Landt M, Birge SJ. Serum leptin levels are reduced in response to exercise training, but not hormone replacement therapy, in older women. J Clin Endocrinol Metab 1996; 81: 3980–5

    Article  PubMed  CAS  Google Scholar 

  37. Ryan AS, Pratley RE, Elahi D, et al. Changes in plasma leptin and insulin action with resistive training in postmenopausal women. Int J Obes 1999; 23: 1–6

    Article  Google Scholar 

  38. Spiegelman BM. PPAR-γ: adipogenic regulator and thiazolidinedione receptor. Diabetes 1998; 47: 507–14

    Article  PubMed  CAS  Google Scholar 

  39. Tontonoz P, Graves RA, Budavari AB, et al. Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPARγ2 and RXRα. Nucleic Acids Res 1994; 22: 5628–34

    Article  CAS  Google Scholar 

  40. Vidal-Puig AJ, Considine RV, Jimenex-Linan M, et al. Peroxisome proliferator-activated receptor gene expression in human tissues: effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J Clin Invest 1997; 99: 2416–22

    Article  PubMed  CAS  Google Scholar 

  41. Park KS, Ciaraldi TP, Lindgren K, et al. Troglitazone effects on gene expression in human skeletal muscle of type II diabetes involve up-regulation of peroxisome proliferator-activated receptor-γ. J Clin Endocrinol Metab 1998; 83: 2830–5

    Article  PubMed  CAS  Google Scholar 

  42. Old LJ. Tumor necrosis factor (TNF). Science 1985; 230: 630–3

    Article  PubMed  CAS  Google Scholar 

  43. Hotamisligil GS, Arner P, Caro JF, et al. Increased tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. J Clin Invest 1995; 95: 2409–15

    Article  PubMed  CAS  Google Scholar 

  44. Peraldi P, Spiegelman B. TNF-α and insulin resistance: summary and future prospects. Mol Cell Biochem 1998; 182: 169–75

    Article  PubMed  CAS  Google Scholar 

  45. Winkler G, Salamon F, Harmos G, et al. Elevated serum tumor necrosis factor-alpha concentrations and bioactivity in Type 2 diabetics and patients with android type obesity. Diabetes Res Clin Practice 1998; 42: 169–74

    Article  CAS  Google Scholar 

  46. Dandona P, Weinstock R, Thusu K, et al. Tumor necrosis factor-α in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 1998; 83: 2907–10

    Article  PubMed  CAS  Google Scholar 

  47. Ciaraldi TP, Carter L, Mudaliar S, et al. Effects of tumor necrosis factor-α on glucose metabolism in cultured human muscle cells from nondiabetic and type 2 diabetic subjects. Endocrinology 1998; 139: 4793–800

    Article  PubMed  CAS  Google Scholar 

  48. Nilsson J, Jovinge S, Niemann A, et al. Relation between plasma tumor necrosis factor-α and insulin sensitivity in elderly men with non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 1998; 18: 1199–202

    Article  PubMed  CAS  Google Scholar 

  49. Kellerer M, Rett K, Renn W, et al. Circulating TNF-α and leptin levels in offspring of NIDDM patients do not correlate to individual insulin sensitivity. Horm Metab Res 1996; 28: 737–43

    Article  PubMed  CAS  Google Scholar 

  50. Randle PJ, Garland PB, Hales CN, et al. The glucose fatty acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963: I: 785–9

    Article  Google Scholar 

  51. Randle PH. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev 1998; 14: 263–83

    Article  PubMed  CAS  Google Scholar 

  52. Roden M, Price TB, Pereghin G, et al. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 1996; 97: 2859–65

    Article  PubMed  CAS  Google Scholar 

  53. Shulman GI. Cellular mechanisms of insulin resistance in humans. Am J Cardiol 1999; 84: 3–10J

    Article  Google Scholar 

  54. Shulman GI, Rothman DL, Jue T, et al. Quantitation of muscle glycogen synthesis in normal subjects and subjects with noninsulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 1990; 322: 223–8

    Article  PubMed  CAS  Google Scholar 

  55. Rothman DL, Shulman RG, Shulman GI. 31P nuclear magnetic resonance measurements of muscle glucose-6-phosphate: evidence for reduced insulin-dependent muscle glucose transportor phosphorylation activity in non-insulin-dependent diabetes mellitus. J Clin Invest 1992; 89: 1069–75

    Article  PubMed  CAS  Google Scholar 

  56. Dresner A, Laurent D, Marcucci M, et al. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 1999; 103: 253–9

    Article  PubMed  CAS  Google Scholar 

  57. Kasuga M, Karleson FA, Kahn CR. Insulin stimulates the phosphorylation of the β-subunit of its own receptor. Science 1982; 217: 185–7

    Article  Google Scholar 

  58. White MF, Maron R, Kahn CR. Insulin rapidly stimulates tyrosine phosphorylation of a Mr 185,000 protein in intact cells. Nature 1985; 318: 183–6

    Article  PubMed  CAS  Google Scholar 

  59. Okada T, Kawano Y, Sakakibara T, et al. Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes: studies with a selective inhibitor wortmannin. J Biol Chem 1994; 269: 3568–73

    PubMed  CAS  Google Scholar 

  60. Brady MJ, Saltiel AR. Closing in on the cause of insulin resistance and type 2 diabetes. J Clin Invest 1999; 104: 675–6

    Article  PubMed  CAS  Google Scholar 

  61. Cheung A, Kusari J, Jansen D, et al. Marked impairment of protein tyrosine phosphatase 1B activity in adipose tissue of obese subjects with and without type 2 diabetes. J Lab Clin Med 1999; 134: 115–23

    Article  PubMed  CAS  Google Scholar 

  62. Goldstein BJ, Ahmad F, Ding W, et al. Regulation of the insulin signaling pathway by cellular protein-tyrosine phosphatases. Mol Cell Biochem 1998; 182: 91–9

    Article  PubMed  CAS  Google Scholar 

  63. Ahmad F, Considine RV, Bauer TL, et al. Improved sensitivity to insulin in obese subjects following weight loss is accompanied by reduced protein-tyrosine phosphatases in adipose tissue. Metabolism 1997; 46: 1140–5

    Article  PubMed  CAS  Google Scholar 

  64. Reynet C, Kahn CR. Rad: a member of the Ras family overexpressed in muscle of type II diabetic humans. Science 1993; 262: 1441–4

    Article  PubMed  CAS  Google Scholar 

  65. Youngren JF, Goldfine ID. The molecular basis of insulin resistance. Sci Med 1997; 4: 18–27

    CAS  Google Scholar 

  66. Maddux BA, Sbraccia P, Kumakura S, et al. Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes. Nature 1995; 373: 448–51

    Article  PubMed  CAS  Google Scholar 

  67. Winder WW, Hardie DG. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol 1999; 277: E1–10

    PubMed  CAS  Google Scholar 

  68. Hardie DG, Carling D. The AMP-activated protein kinase: fuel gauge of the mammalian cell? Eur J Biochem 1997; 246: 259–73

    Article  PubMed  CAS  Google Scholar 

  69. Winder WW, Hardie DG. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol 1996; 270: E299–304

    PubMed  CAS  Google Scholar 

  70. Rasmussen BB, Winder WW. Effect of exercise intensity on skeletal muscle malonyl-CoA and acetyl-CoA carboxylase. J Appl Physiol 1997; 83: 1104–9

    PubMed  CAS  Google Scholar 

  71. Hayashi T, Hirshman MF, Kurth EJ, et al. Evidence for 5’ AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 1998; 47: 1369–73

    Article  PubMed  CAS  Google Scholar 

  72. Hayashi T, Hirshman MF, Habinowski SA, et al. The α2 isoform of the 5’ AMP-activated protein kinase (AMPK) may mediate contraction-stimulated glucose transport in skeletal muscle [abstract]. Diabetes 1999; 48: A13

    Google Scholar 

  73. Salt IP, Johnson G, Ashcroft SJH, et al. AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic β cells, and may regulate insulin release. Biochem J 1998; 335: 533–9

    PubMed  CAS  Google Scholar 

  74. Folsum AR, Prineas RJ, Kaye SA, et al. Body fat distribution and self-reported prevalence of hypertension, heart attack, and other heart disease in women. Int J Epidemiol 1989; 18: 361–7

    Article  Google Scholar 

  75. Lundgren H, Bengtsson C, Blohme G, et al. Adiposity and adipose tissue distribution in relation to incidence of diabetes in women: results from a prospective population study in Gothenburg, Sweden. Int J Obes 1989; 13: 413–23

    PubMed  CAS  Google Scholar 

  76. Haarbo J, Hassager C, Riis BJ, et al. Relation of body fat distribution to serum lipids and lipoproteins in elderly women. Atherosclerosis 1989; 80: 57–62

    Article  PubMed  CAS  Google Scholar 

  77. Landsberg L. Diet, obesity and hypertension: a hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med 1986; 61: 1081–90

    PubMed  CAS  Google Scholar 

  78. Vague J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout and uric calculus disease. Am J Clin Nutr 1956; 4: 20–4

    PubMed  CAS  Google Scholar 

  79. Bjorntorp P. Regional fat distribution: implications for type II diabetes. Int J Obes Relat Metab Disord 1992; 16 Suppl. 4: S19–27

    PubMed  Google Scholar 

  80. Kissebah AH, Vydelingum N, Murray R, et al. Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab 1982; 54: 254–60

    Article  PubMed  CAS  Google Scholar 

  81. Krotkiewski M, Bjorntorp P, Sjostrom L, et al. Impact of obesity on metabolism in men and women: importance of regional adipose tissue distribution. J Clin Invest 1983; 72: 1150–62

    Article  PubMed  CAS  Google Scholar 

  82. Despres JP, Nadeau A, Tremblay A, et al. Role of deep abdominal fat in association between regional adipose tissue distribution and glucose tolerance in obese women. Diabetes 1989; 38: 304–9

    Article  PubMed  CAS  Google Scholar 

  83. Cefalu WT, Wang ZQ, Werbel S, et al. Contribution of visceral fat mass to the insulin resistance of aging. Metabolism 1995; 44: 954–9

    Article  PubMed  CAS  Google Scholar 

  84. Abate N, Garg A, Peshock RM, et al. Relationships of generalized and regional adiposity to insulin sensitivity in men. J Clin Invest 1995; 96: 88–98

    Article  PubMed  CAS  Google Scholar 

  85. Goodpaster BH, Thaete FL, Simoneau J-A, et al. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes 1997; 46: 1579–85

    Article  PubMed  CAS  Google Scholar 

  86. Coon PJ, Rogus EM, Drinkwater D, et al. Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age. J Clin Endocrinol Metab 1992; 75: 1125–32

    Article  PubMed  CAS  Google Scholar 

  87. Kohrt WM, Kirwan JP, Staten MA, et al. Insulin resistance in aging is related to abdominal obesity. Diabetes 1993; 42: 273–81

    Article  PubMed  CAS  Google Scholar 

  88. Jequier E. Energy metabolism in obese patients before and after weight loss, and in patients who have relapsed. Int J Obesity 1990; 14 (S1): 59–67

    Google Scholar 

  89. Despres JP, Pouliot MC, Moorjani S, et al. Loss of abdominal fat and metabolic response to exercise training in obese women. Am J Physiol 1991; 261 (2 Pt 1): E159–67

    PubMed  CAS  Google Scholar 

  90. Andersson B, Xu X, Rebuffe-Scrive M, et al. The effects of exercise training on body composition and metabolismin men and women. Int J Obes 1991; 15: 75–81

    PubMed  CAS  Google Scholar 

  91. Lehmann R, Vokac A, Niedermann K, et al. Loss of abdominal fat and improvement of the cardiovascular risk profile by regular moderate exercise training in patients with NIDDM. Diabetologia 1995; 38: 1313–9

    Article  PubMed  CAS  Google Scholar 

  92. Bosello O, Zamboni M, Armellini F, et al. Modifications of abdominal fat and hepatic insulin clearance during severe caloric restriction. Ann Nutr Metab 1990; 34: 359–65

    Article  PubMed  CAS  Google Scholar 

  93. Gray DS, Fujioka K, Colletti PM, et al. Magnetic-resonance imaging used for determining fat distribution in obesity and diabetes. Am J Clin Nutr 1991; 54: 623–7

    PubMed  CAS  Google Scholar 

  94. Hendler RG, Welle SL, Statt MC, et al. The effects of weight reduction to ideal body weight on body fat distribution. Metabolism 1995; 44: 1413–6

    Article  PubMed  CAS  Google Scholar 

  95. van der Kooy K, Leenen R, Seidell JC, et al. Waist-to-hip ratio is a poor predictor of changes in visceral fat. Am J Clin Nutr 1993; 57: 327–33

    PubMed  Google Scholar 

  96. Schwartz RS, Shuman WP, Larson V, et al. The effect of intensive endurance exercise training on body fat distribution in young and older men. Metabolism 1991; 40: 545–51

    Article  PubMed  CAS  Google Scholar 

  97. Kohrt WM, Obert KA, Holloszy JO. Exercise training improves fat distribution patterns in 60- to 70-year-old men and women. J Gerontol 1992; 47 (4): M99–105

    Article  PubMed  CAS  Google Scholar 

  98. Moody DL, Kollias J, Buskirk ER. The effect of a moderate exercise program on body weight and skinfold thickness in overweight college women. Med Sci Sports Exerc 1972; 4: 210–3

    CAS  Google Scholar 

  99. Treuth MS, Ryan AS, Pratley RE, et al. Effects of strength training on total and regional body composition in older men. J Appl Physiol 1994; 77: 614–20

    PubMed  CAS  Google Scholar 

  100. Ryan AS, Pratley RE, Elahi D, et al. Resistive training increases fat-free mass and maintains RMR despite weight loss in postmenopausal women. J Appl Physiol 1995; 79: 818–23

    PubMed  CAS  Google Scholar 

  101. Nelson ME, Fiatarone MA, Morganti CM, et al. Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures: a randomized controlled trial. JAMA 1994; 272: 1909–14

    Article  PubMed  CAS  Google Scholar 

  102. Yarasheski KE, Campbell JA, Kohrt WM. Effect of resistance exercise and growth hormone on bone density in older men. Clin Endocrinol 1997; 47: 223–9

    Article  CAS  Google Scholar 

  103. Campbell WW, Crim MC, Young VR, et al. Increased energy requirements and changes in body composition with resistance training in older adults. Am J Clin Nutr 1994; 60: 167–75

    PubMed  CAS  Google Scholar 

  104. Hurley BF, Redmond RA, Pratley RE, et al. Effects of strength training on muscle hypertrophy and muscle cell disruption in older men. Int J Sports Med 1995; 16: 378–84

    Article  PubMed  CAS  Google Scholar 

  105. Treuth MS, Hunter GR, Kekes-Szabo T, et al. Reduction in intra-abdominal adipose tissue after strength training in older women. J Appl Physiol 1995; 78: 1425–31

    PubMed  CAS  Google Scholar 

  106. Hill JO, Sparling PB, Shields TW, et al. Effects of exercise and food restriction on body composition and metabolic rate in obese women. Am J Clin Nutr 1987; 46: 622–30

    PubMed  CAS  Google Scholar 

  107. Ballor DL, Poehlman ET. Exercise-training enhances fat-free mass preservation during diet-induced weight loss: a meta-analytical finding. Int J Obes 1994; 18: 35–40

    CAS  Google Scholar 

  108. Ross R, Rissanen J. Mobilization of visceral and subcutaneous adipose tissue in response to energy restriction and exercise. Am J Clin Nutr 1994; 60: 695–703

    PubMed  CAS  Google Scholar 

  109. Ryan AS, Nicklas BJ. Age-related changes in fat deposition in mid-thigh muscle in women: relationships with metabolic cardiovascular disease risk factors. Int J Obes 1999; 23: 126–32

    Article  CAS  Google Scholar 

  110. Simoneau J-A, Colberg SR, Thaete FL, et al. Skeletal muscle glycolytic and oxidative enzyme capacities and determinants of insulin sensitivity and muscle composition in obese women. FASEB J 1995; 9: 273–8

    PubMed  CAS  Google Scholar 

  111. Rice CL, Cunningham DA, Paterson DH, et al. Arm and leg composition determined by computed tomography in young and elderly men. Clin Physiol 1989; 9: 207–20

    Article  PubMed  CAS  Google Scholar 

  112. Imamura K, Ashida H, Ishikawa T, et al. Human major psoas muscle and sacrospinalis muscle in relation to age: a study by computed tomography. J Gerontol 1983; 38: 678–81

    Article  PubMed  CAS  Google Scholar 

  113. Kelley DE, Slasky BS, Janosky J. Skeletal muscle density: effects of obesity and non-insulin-dependent diabetes mellitus. Am J Clin Nutr 1991; 54: 509–15

    PubMed  CAS  Google Scholar 

  114. Goodpaster BH, Kelley DE, Wing RR, et al. Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 1999; 48: 839–47

    Article  PubMed  CAS  Google Scholar 

  115. Ryan AS, Nicklas BJ, Berman DM, et al. Weight loss and walking reduce fat deposition in the mid-thigh in overweight older women. Am J Clin Nutr 2000; 72: 708–13

    PubMed  CAS  Google Scholar 

  116. Henry RR, Wallace P, Olefsky JM. Effects of weight loss on mechanisms of hyperglycemia in obese non-insulin-dependent diabetes mellitus. Diabetes 1986; 35: 990–6

    Article  PubMed  CAS  Google Scholar 

  117. Olefsky J, Reaven GM, Farquhar JW. Effects of weight reduction in obesity: studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects. J Clin Invest 1974; 53: 64–76

    Article  PubMed  CAS  Google Scholar 

  118. Wing RR, Koesk R, Epstein LH, et al. Long-term effects of modest weight loss in type II diabetic patients. Arch Intern Med 1987; 147: 1749–53

    Article  PubMed  CAS  Google Scholar 

  119. Colman E, Katzel LI, Rogus E, et al. Weight loss reduces abdominal fat and improves insulin action in middle-aged and older men with impaired glucose tolerance. Metabolism 1995; 44: 1502–8

    Article  PubMed  CAS  Google Scholar 

  120. Hughes TA, Gwynne JT, Switzen BR, et al. Effect of caloric restriction and weight loss on glycemic control, insulin release, resistance and atherosclerotic risk in obese patients with type II diabetes mellitus. Am J Med 1984; 77: 7–17

    Article  PubMed  CAS  Google Scholar 

  121. Numata K, Tanaka K, Saito M, et al. Very low calorie diet-induced weight loss reverses exaggerated insulin secretion in response to glucose. Int J Obes 1993; 17: 103–8

    CAS  Google Scholar 

  122. Kelley DE, Wing R, Buonocore C, et al. Relative effects of caloric restriction and weight loss in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1993; 77: 1287–93

    Article  PubMed  CAS  Google Scholar 

  123. American Diabetes Association. Nutrition recommendations and principles for people with diabetes mellitus. Diabetes Care 1994; 17: 519–22

    Article  Google Scholar 

  124. Berry EM. Dietary fatty acids in the management of diabetes. Am J Clin Nutr 1997; 66: 991S–7S

    PubMed  CAS  Google Scholar 

  125. Clarke SD, Baillie R, Jump DB, et al. Fatty acid regulation of gene expression: its role in fuel partitioning and insulin resistance. Ann NY Acad Sci 1997 Sep 20; 827: 178–87

    Article  PubMed  CAS  Google Scholar 

  126. Tremblay A. Nutritional determinants of the insulin resistance syndrome. Int J Obes Relat Metab Disord 1995; 19 Suppl. 1: S60–8

    PubMed  Google Scholar 

  127. Storlien LH, Baur LA, Kriketos AD, et al. Dietary fats and insulin action. Diabetologia 1996; 39: 621–31

    Article  PubMed  CAS  Google Scholar 

  128. Daly ME, Vale C, Walker M, et al. Dietary carbohydrates and insulin sensitivity: a review of the evidence and clinical implications. Am J Clin Nutr 1997; 66: 1072–85

    PubMed  CAS  Google Scholar 

  129. Fukagawa NK, Anderson JW, Hageman G, et al. High-carbodyrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults. Am J Clin Nutr 1990; 52: 524–8

    PubMed  CAS  Google Scholar 

  130. Baan CA, Stolk RP, Grobbee DE, et al. Physical activity in elderly subjects with impaired glucose tolerance and newly diagnosed diabetes mellitus. Am J Epidemiol 1999; 149: 219–27

    Article  PubMed  CAS  Google Scholar 

  131. Helmrich SP, Ragland DD, Leung RW, et al. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 1991; 325: 147–52

    Article  PubMed  CAS  Google Scholar 

  132. King DS, Dalsky GP, Staten MA, et al. Insulin action and secretion in endurance-trained and untrained humans. J Appl Physiol 1987; 63: 2247–52

    PubMed  CAS  Google Scholar 

  133. Seals DR, Hagberg JM, Allen WK, et al. Glucose tolerance in young and older athletes and sedentary men. J Appl Physiol 1984; 56: 1521–5

    PubMed  CAS  Google Scholar 

  134. Pratley RE, Hagberg JM, Rogus EM, et al. Enhanced insulin sensitivity and lower waist-to-hip ratio in master athletes. Am J Physiol 1995; 268 (3 Pt 1): E484–90

    PubMed  CAS  Google Scholar 

  135. Rodnick KJ, Haskell WL, Swislocki ALM, et al. Improved insulin action in muscle, liver, and adipose tissue in physically trained human subjects. Am J Physiol 1987; 253 (5 Pt 1): E489–95

    PubMed  CAS  Google Scholar 

  136. Tokuyama K, Higaki Y, Fujitani J, et al. Intravenous glucose tolerance test-derived glucose effectiveness in physically trained humans. Am J Physiol 1993; 265 (2 Pt 1): E298–303

    PubMed  CAS  Google Scholar 

  137. Mikines KJ, Sonne B, Farrell PA, et al. Effect of physical exercise on sensitivity and responsiveness to insulin in humans. Am J Physiol 1988; 254: E248–59

    PubMed  CAS  Google Scholar 

  138. Mikines KJ, Sonne B, Tronier B, et al. Effects of acute exercise and detraining on insulin action in trained men. J Appl Physiol 1989; 66: 704–11

    Article  PubMed  CAS  Google Scholar 

  139. Ryan AS, Muller DC, Nicklas BJ, et al. Insulin response and glucose utilization in highly trained female athletes aged 18 to 69 years [abstract]. Diabetes 1996; 45: 325A

    Google Scholar 

  140. Mayer-Davis EJ, D’Agostino R, Karter AJ, et al. Intensity and amount of physical activity in relation to insulin sensitivity. JAMA 1998; 279: 669–74

    Article  PubMed  CAS  Google Scholar 

  141. Tonino RP. Effect of physical training on the insulin resistance of aging. Am J Physiol 1989; 256 (3 Pt 1): E352–6

    PubMed  CAS  Google Scholar 

  142. DeFronzo RA, Sherwin RS, Kraemer N. Effect of physical training on insulin action in obesity. Diabetes 1987; 36: 1379–85

    Article  PubMed  CAS  Google Scholar 

  143. Kahn SE, Larson VG, Beard JC, et al. Effect of exercise on insulin action, glucose tolerance, and insulin secretion in aging. Am J Physiol 1990; 258 (6 Pt 1): E937–43

    PubMed  CAS  Google Scholar 

  144. Kirwan JP, Kohrt WM, Wojta DM, et al. Endurance exercise reduces glucose stimulated insulin levels in 60–70 year old men and women. J Gerontol 1993; 48 (3): M84–90

    Article  PubMed  CAS  Google Scholar 

  145. Krotkiewski M, Lonnrolth P, Mandroukas K, et al. The effects of physical training on insulin secretion and effectiveness and on glucose metabolism in obesity and type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1985: 28: 881–90

    Article  PubMed  CAS  Google Scholar 

  146. Trovati M, Carta W, Cavalot F, et al. Influence of physical training on blood glucose control, glucose tolerance, insulin secretion, and insulin action in non-insulin-dependent diabetic patients. Diabetes Care 1984; 7: 416–20

    Article  PubMed  CAS  Google Scholar 

  147. Bogardus C, Ravussin E, Robbins DC, et al. Effects of physical training and diet therapy on carbohydrate metabolism in patients with glucose intolerance and non-insulin dependent diabetes mellitus. Diabetes 1984; 33: 311–8

    Article  PubMed  CAS  Google Scholar 

  148. Dela F, Larsem KK, Mikines KJ, et al. Insulin stimulated muscle glucose clearance in patients with type 2 diabetes mellitus: effects of one-legged physical training. Diabetes 1995; 44: 1010–20

    Article  PubMed  CAS  Google Scholar 

  149. Oppert JM, Nadeau A, Tremblay A, et al. Negative energy balance with exercise in identical twins: plasma glucose and insulin responses. Am J Physiol 1997; 272: E248–54

    PubMed  CAS  Google Scholar 

  150. Hughes VA, Fiatarone MA, Fielding RA, et al. Long-term effects of a high-carbohydrate diet and exercise on insulin action in older subjects with impaired glucose tolerance. Am J Clin Nutr 1995; 62: 426–33

    PubMed  CAS  Google Scholar 

  151. Arciero PJ, Vukovich MD, Holloszy JO, et al. Comparison of short-term diet and exercise on insulin action in individuals with abnormal glucose tolerance. J Apply Physiol 1999; 86: 1930–5

    CAS  Google Scholar 

  152. Devlin JT, Horton ES. Effect of prior high-intensity exercise on glucose metabolism in normal and insulin-resistant men. Diabetes 1985; 34: 973–9

    Article  PubMed  CAS  Google Scholar 

  153. Devlin JT, Hirshman M, Horton ED, et al. Enhanced peripheral and splanchnic insulin sensitivity in NIDDM men after single bout of exercise. Diabetes 1987; 36: 434–9

    Article  PubMed  CAS  Google Scholar 

  154. Kang J, Robertson RJ, Hagberg JM, et al. Effect of exercise intensity on glucose and insulin metabolism in obese individuals and obese NIDDM patients. Diabetes Care 1996; 19: 341–9

    Article  PubMed  CAS  Google Scholar 

  155. Kirwan JP, Hickner RC, Yarasheski KE, et al. Eccentric exercise induces transient insulin resistance in healthy individuals. J Appl Physiol 1992; 72: 2197–202

    Article  PubMed  CAS  Google Scholar 

  156. Tuominen JA, Ebeling P, Bourey R, et al. Postmarathon paradox: insulin resistance in the face of glycogen depletion. Am J Physiol 1996; 270: E336–43

    PubMed  CAS  Google Scholar 

  157. Miller J, Pratley RE, Goldberg AP, et al. Strength training increases insulin sensitivity in healthy 50–65 year old men. J Appl Physiol 1994; 77: 1122–7

    PubMed  CAS  Google Scholar 

  158. Ryan AS, Pratley RE, Goldberg AP, et al. Resistive training increases insulin action in postmenopausal women. J Gerontol Med Sci 1996; 51A: M199–205

    Article  CAS  Google Scholar 

  159. Zachwiega JJ, Toffolo G, Cobelli C, et al. Resistance exercise and growth hormone administration in older men: effects on insulin sensitivity and secretion during a stable-label intravenous glucose tolerance test. Metabolism 1996; 45: 254–60

    Article  Google Scholar 

  160. Wallace MB, Mills BD, Browning CL. Effects of cross-training on markers of insulin resistance/hyperinsulinemia. Med Sci Sports Exerc 1997; 29: 1170–5

    Article  PubMed  CAS  Google Scholar 

  161. Torjesen PA, Birkeland KI, Anderssen SA, et al. Lifestyle changes may reverse development of the insulin resistance syndrome. Diabetes Care 1997; 20: 26–31

    Article  PubMed  CAS  Google Scholar 

  162. Dengel DR, Galecki AT, Hagberg JM, et al. The independent and combined effects of weight loss and aerobic exercise on blood pressure and oral glucose tolerance in older men. Am J Hypertens 1998; 11: 1405–12

    Article  PubMed  CAS  Google Scholar 

  163. Katzel LI, Bleecker ER, Colman EG, et al. Effects of weight loss vs aerobic exercise training on risk factors for coronary disease in healthy, obese, middle-aged and older men. JAMA 1995; 274: 1915–21

    Article  PubMed  CAS  Google Scholar 

  164. Rice B, Janssen I, Hudson R, et al. Effects of aerobic or resistance exercise and/or diet on glucose tolerance and plasma insulin levels in obese men. Diabetes Care 1999; 22: 684–91

    Article  PubMed  CAS  Google Scholar 

  165. Weinstock RS, Dai H, Wadden TA. Diet and exercise in the treatment of obesity: effects of 3 interventions on insulin resistance. Arch Intern Med 1998; 158: 2477–83

    Article  PubMed  CAS  Google Scholar 

  166. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–9

    Article  PubMed  CAS  Google Scholar 

  167. Dengel DR, Pratley RE, Hagberg JM, et al. Distinct effects of aerobic exercise training and weight loss on glucose homeostasis in obese sedentary men. J Appl Physiol 1996; 81: 318–25

    PubMed  CAS  Google Scholar 

  168. Caro JF, Sinha MK, Raju SM, et al. Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes. J Clin Invest 1987; 79: 1330–7

    Article  PubMed  CAS  Google Scholar 

  169. Johnson AB, Argyraki M, Thow JC, et al. Effects of intensive dietary treatment on insulin-stimulated skeletal muscle glycogen synthase activation and insulin secretion in newly presenting type 2 diabetic patients. Diabet Med 1990; 7: 420–8

    Article  PubMed  CAS  Google Scholar 

  170. Garvey WT, Maianu L, Hancock JA, et al. Gene expression of GLUT4 in skeletal muscle from insulin-resistant patients with obesity, IGT, GDM, and NIDDM. Diabetes 1992; 41: 465–75

    Article  PubMed  CAS  Google Scholar 

  171. Pederson O, Bak J, Andersen P, et al. Evidence against altered expression of GLUT1 and GLUT4 in skeletal muscle of patients with obesity or NIDDM. Diabetes 1990; 39: 865–70

    Article  Google Scholar 

  172. Andersen PH, Lund S, Vestergaard H, et al. Expression of the major insulin regulatable glucose transporter (GLUT4) in skeletal muscle of noninsulin-dependent diabetic patients and healthy subjects before and after insulin infusion. J Clin Endocrinol Metab 1993; 77: 27–32

    Article  PubMed  CAS  Google Scholar 

  173. Houmard JA, Weidner MD, Dolan PL, et al. Skeletal muscle GLUT4 protein concentration and aging in humans. Diabetes 1995; 44: 555–60

    Article  PubMed  CAS  Google Scholar 

  174. Friedman JE, Dohm GL, Leggett-Frazier N, et al. Restoration of insulin responsiveness in skeletal muscle in morbidly obese patients after weight loss. J Clin Invest 1992; 89: 701–5

    Article  PubMed  CAS  Google Scholar 

  175. Ebeling P, Bourey R, Koranyi L, et al. Mechanism of enhanced insulin sensitivity in athletes. J Clin Invest 1993; 92: 1623–31

    Article  PubMed  CAS  Google Scholar 

  176. Houmard JA, Shinebarger MH, Dolan PL, et al. Exercise training increases GLUT-4 protein concentration in previously sedentary middle-aged men. Am J Physiol 1993; 264: E896–901

    PubMed  CAS  Google Scholar 

  177. Dela F, Ploug T, Handberg A, et al. Physical training increases muscle GLUT-4 protein and mRNA in patients with NIDDM. Diabetes 1994; 43: 862–5

    Article  PubMed  CAS  Google Scholar 

  178. Hughes VA, Fiatarone MA, Fielding RA, et al. Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance. Am J Physiol 1993; 264: E855–62

    PubMed  CAS  Google Scholar 

  179. Ivey JL. Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. Sports Med 1997; 24: 321–36

    Article  Google Scholar 

  180. Hickey MS, Weidner MD, Gavigan KE, et al. The insulin action-fiber type relationship in humans is muscle group specific. Am J Physiol 1995; 269: E150–4

    PubMed  CAS  Google Scholar 

  181. Marin P, Andersson B, Krotkiewski M, et al. Muscle fiber composition and capillary density in women andmen with NIDDM. Diabetes Care 1994; 17: 382–6

    Article  PubMed  CAS  Google Scholar 

  182. Simoneau J, Kelley DE. Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. J Appl Physiol 1997; 83: 166–71

    PubMed  CAS  Google Scholar 

  183. Coggan AR, Spina RJ, King DS, et al. Histochemical and enzymatic comparison of the gastrocnemius muscle of young and elderly men and women. J Gerontol Biol Sci 1992; 46B: 71–6

    Google Scholar 

  184. Coggan AR, Spina RJ, King DS, et al. Skeletal muscle adaptations to endurance training in 60- to 70-yr-old men and women. J Appl Physiol 1992; 72: 1780–6

    PubMed  CAS  Google Scholar 

  185. Hardin DS, Azzarelli B, Edwards J, et al. Mechanisms of enhanced insulin sensitivity in endurance-trained athletes: effects on blood flow and differential expression of GLUT4 in skeletal muscles. J Clin Endocrinol Metab 1995; 80: 2437–46

    Article  PubMed  CAS  Google Scholar 

  186. American College of Sports Medicine. Guidelines for exercise testing and prescription, 1995. 5th ed. Philadelphia: Lea & Febiger, 1995

    Google Scholar 

  187. American Diabetes Association. Diabetes mellitus and exercise. Diabetes Care 1997; 20: 1908–12

    Google Scholar 

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Acknowledgements

I would like to thank Dr Andrew Goldberg for his insightful comments and acknowledge the support of NIH grant K01-AG00747, and the Department of Veterans Affairs, Geriatrics Research, Education, and Clinical Center at Baltimore.

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Correspondence to Alice S. Ryan.

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Ryan, A.S. Insulin Resistance with Aging. Sports Med 30, 327–346 (2000). https://doi.org/10.2165/00007256-200030050-00002

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