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Should the Insulin Resistance Syndrome be Treated in the Elderly?

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Abstract

The insulin resistance syndrome represents the co-occurrence of hyperglycaemia, hypertension, central and overall obesity, and dyslipidaemia characterised by low high density lipoprotein-cholesterol (HDL-C) and high triglyceride levels. Epidemiologic studies have revealed an increasing prevalence of the insulin resistance syndrome in elderly populations. Indeed, recent data indicate that over 40% of US adults aged ≥60 years meet current criteria for the insulin resistance syndrome. Patients with this syndrome are at increased risk for the development of both cardiovascular disease (CVD) and type 2 diabetes mellitus, two of the most significant health problems among people >65 years of age. Identification and treatment of the insulin resistance syndrome may thus represent an important approach to reducing the overall burden of morbidity and mortality in the elderly.

While development of the insulin resistance syndrome is partly determined by modifiable environmental factors, there may be a genetic basis for the syndrome, with high levels of concordance among monozygotic twins. Ongoing research focusing on the pathophysiology of this syndrome has implicated insulin resistance as the central disorder underlying both the development of diabetes as well as the pro-thrombotic endothelial dysfunction characteristic of CVD.

Studies aimed at reversing insulin resistance have identified weight loss, exercise and pharmacological treatment with metformin, thiazolidinediones, HMG-CoA reductase inhibitors (statins) and ACE inhibitors as potential therapies to prevent the development of type 2 diabetes. However, although insulin sensitisation may be beneficial for preventing type 2 diabetes, there are no data yet available to show whether this strategy will reduce the incidence of CVD.

Increased exercise and other healthy lifestyle changes form the cornerstone of therapy for elderly patients with the insulin resistance syndrome. In addition, active identification and aggressive management of traditional cardiovascular risk factors are the current standard of care. For elderly patients, recent studies have conclusively demonstrated the safety and efficacy of pharmacological management of elevated blood pressure and cholesterol levels.

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References

  1. Murray CJL, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 1997; 349: 1269–76

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Haffner SM, Valdez RA, Hazuda HP, et al. Prospective analysis of the insulin resistance syndrome (syndrome X). Diabetes 1992; 41: 715–22

    Article  PubMed  CAS  Google Scholar 

  4. Saad MF, Knowler WC, Pettitt DJ, et al. A two-step model for development of non-insulin dependent diabetes mellitus. Am J Med 1991; 90: 229–35

    PubMed  CAS  Google Scholar 

  5. Salonen JT, Lakka TA, Laaka H-M, et al. Hyperinsulinemia is associated with the incidence of hypertension and dyslipidemia in middle-aged men. Diabetes 1998; 47: 270–5

    Article  PubMed  CAS  Google Scholar 

  6. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults: The Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care 1998; 21(4): 518–24

    Article  PubMed  CAS  Google Scholar 

  7. Haffner SM, Stern MP, Hazuda HP, et al. Cardiovascular risk factors in confirmed prediabetic individuals: does the clock for coronary heart disease start ticking before the onset of diabetes? JAMA 1990; 263: 2893–8

    Article  PubMed  CAS  Google Scholar 

  8. McPhillips JB, Barrett-Connor E, Wingard DL. Cardiovascular disease risk factors prior to the diagnosis of impaired glucose tolerance and non-insulin-dependent diabetes mellitus in a community of older adults. Am J Epidemiol 1990; 131: 443–53

    PubMed  CAS  Google Scholar 

  9. Mykkanen L, Kuusisto J, Pyorala K, et al. Cardiovascular disease risk factors as predictors of type 2 (non-insulin-dependent) diabetes mellitus in elderly subjects. Diabetologia 1993; 36: 553–9

    Article  PubMed  CAS  Google Scholar 

  10. Haffner SM, Mykkanen L, Festa A, et al. Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state. Circulation 2000; 101: 975–80

    Article  PubMed  CAS  Google Scholar 

  11. Wilson PWF, D’Agostino RB, Levy D, et al. Prediction of coronary heart disease risk using risk factor categories. Circulation 1998; 97: 1837–47

    Article  PubMed  CAS  Google Scholar 

  12. Wilson PWF, Hoeg JM, D’Agostino RB, et al. Cumulative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis. N Engl J Med 1997; 337: 516–22

    Article  PubMed  CAS  Google Scholar 

  13. Meigs JB. Invited commentary: insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am J Epidemiol 2000; 152(10): 908–11

    Article  PubMed  CAS  Google Scholar 

  14. Hu FB, Manson JE, Stampfer MJ, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med 2001; 345(11): 790–7

    Article  PubMed  CAS  Google Scholar 

  15. Liese AD, Mayer-Davis EJ, Tyroler HA, et al. Familial components of the multiple metabolic syndrome: the ARIC study. Diabetologia 1997; 40(8): 963–70

    Article  PubMed  CAS  Google Scholar 

  16. Carmelli D, Cardon LR, Fabsitz R. Clustering of hypertension, diabetes, and obesity in adult male twins: same genes or same environments? Am J Hum Genet 1994; 55(3): 566–73

    PubMed  CAS  Google Scholar 

  17. Edwards KL, Newman B, Mayer E, et al. Heritability of factors of the insulin resistance syndrome in women twins. Genet Epidemiol 1997; 14(3): 241–53

    Article  PubMed  CAS  Google Scholar 

  18. Mitchell BD, Kammerer CM, Mahaney MC, et al. Genetic analysis of the IRS: pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures. Arterioscler Thromb Vasc Biol 1996; 16(2): 281–8

    Article  PubMed  CAS  Google Scholar 

  19. Kissebah AH, Sonnenberg GE, Myklebust J, et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci U S A 2000; 97(26): 14478–83

    Article  PubMed  CAS  Google Scholar 

  20. Arya R, Blangero J, Williams K, et al. Factors of insulin resistance syndrome: related phenotypes are linked to genetic locations on chromosomes 6 and 7 in nondiabetic Mexican-Americans. Diabetes 2002; 51(3): 841–7

    Article  PubMed  CAS  Google Scholar 

  21. Meigs JB, Mittleman MA, Nathan DM, et al. Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. JAMA 2000; 283: 221–8

    Article  PubMed  CAS  Google Scholar 

  22. Sobel BE. Increased plasminogen activator inhibitor-1 and vasculopathy: a reconcilable paradox. Circulation 1999; 99: 2496–8

    Article  PubMed  CAS  Google Scholar 

  23. Pickup JC, Mattock MB, Chusney GD, et al. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 1997; 40(11): 1286–92

    Article  PubMed  CAS  Google Scholar 

  24. Yudkin JS, Stehouwer CDA, Emis JJ, et al. C-reactive protein in healthy subjects: associations with obesity, insulin resistance and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999; 19: 972–8

    Article  PubMed  CAS  Google Scholar 

  25. Pinkney JH, Stehouwer CD, Coppack SW, et al. Endothelial dysfunction: cause of the insulin resistance syndrome. Diabetes 1997; 46Suppl. 2: S9–13

    PubMed  CAS  Google Scholar 

  26. Howard G, O’Leary DH, Zaccaro D, et al. Insulin sensitivity and atherosclerosis: The Insulin Resistance Atherosclerosis Study (IRAS) Investigators. Circulation 1996; 93(10): 1809–17

    Article  PubMed  CAS  Google Scholar 

  27. Rewers M, D’Agostino J, Burke G, et al. Coronary artery disease is associated with low insulin sensitivity independent of insulin levels and cardiovascular risk factors [abstract]. Diabetes 1996; 45Suppl. 2: 52A

    Google Scholar 

  28. Meigs JB, Larson MG, D’Agostino RB, et al. Coronary artery calcification in type 2 diabetes and insulin resistance: the Framingham Offspring Study. Diabetes Care 2002; 25(8): 1313–9

    Article  PubMed  CAS  Google Scholar 

  29. Despres J-P, Lamarche B, Mauriege P, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996; 334: 952–7

    Article  PubMed  CAS  Google Scholar 

  30. Pyorala M, Pyorala K, Laakso M. Hyperinsulinemia as a predictor of coronary heart disease risk: 22-year follow-up results of the Helsinki Policeman Study. Circulation 1996; 94Suppl. 1: 1–213

    Google Scholar 

  31. Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288(21): 2709–16

    Article  PubMed  Google Scholar 

  32. Balkau B, Charles MA. Comment on the provisional report from the WHO consultation: European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999; 16(5): 442–3

    Article  PubMed  CAS  Google Scholar 

  33. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications (Pt 1): diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15(7): 539–53

    Article  PubMed  CAS  Google Scholar 

  34. National Cholesterol Education Program. Executive summary of the Third Report of The National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285(19): 2486–97

    Article  Google Scholar 

  35. Meigs JB. Epidemiology of the metabolic syndrome. Am J Manag Care 2002; 8(11): S283–292

    PubMed  Google Scholar 

  36. Meigs JB. Epidemiology of the insulin resistance syndrome. Curr Diab Rep 2003; 3: 73–9

    Article  PubMed  Google Scholar 

  37. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346(6): 393–403

    Article  PubMed  CAS  Google Scholar 

  38. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344(18): 1343–50

    Article  PubMed  CAS  Google Scholar 

  39. Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20(4): 537–44

    Article  PubMed  CAS  Google Scholar 

  40. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34): UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352(9131): 854–65

    Google Scholar 

  41. American Geriatrics Society Panel on Exercise and Osteoarthritis. Exercise prescription for older adults with osteoarthitis pain: consensus practice recommendations. J Am Geriatr Soc 2001; 49: 808–23

    Article  Google Scholar 

  42. Gill TM, DiPietro L, Krumholz HM. Role of exercise stress testing and safety monitoring for older persons starting an exercise program. JAMA 2000; 284: 342–9

    Article  PubMed  CAS  Google Scholar 

  43. Ghazzi MN, Perez JE, Antonucci TK, et al. Cardiac and glycemic benefits of troglitazone treatment in NIDDM. Diabetes 1997; 46: 433–9

    Article  PubMed  CAS  Google Scholar 

  44. Minamikawa J, Tanaka S, Yamauchi M, et al. Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab 1998; 83(5): 1818–20

    Article  PubMed  CAS  Google Scholar 

  45. Kreider M, Heise M. Rosiglitazone in the management of older patients with type 2 diabetes mellitus. Int J Clin Pract 2002; 56(7): 538–41

    PubMed  CAS  Google Scholar 

  46. Bulpitt C, Fletcher A, Beckett N, et al. Hypertension in the Very Elderly Trial (HYVET): protocol for the main trial. Drugs Aging 2001; 18(3): 151–64

    Article  PubMed  CAS  Google Scholar 

  47. Gueyffier F, Bulpitt C, Boissel JP, et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group. Lancet 1999; 353(9155): 793–6

    Article  PubMed  CAS  Google Scholar 

  48. de Vegt F, Dekker JM, Stehouwer CD, et al. The 1997 American Diabetes Association criteria versus the 1985 World Health Organization criteria for the diagnosis of abnormal glucose tolerance: poor agreement in the Hoorn Study. Diabetes Care 1998; 21(10): 1686–90

    Article  PubMed  Google Scholar 

  49. Meigs JB, Nathan DM, D’Agostino RB, et al. Fasting and postchallenge glycemia and cardiovascular disease risk: the Framingham Offspring Study. Diabetes Care 2002; 25: 1845–50

    Article  PubMed  Google Scholar 

  50. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287(3): 356–9

    Article  PubMed  Google Scholar 

  51. Mokdad AH, Serdula MK, Dietz WH, et al. The spread of the obesity epidemic in the United States, 1991–1998. JAMA 1999; 282(16): 1519–22

    Article  PubMed  CAS  Google Scholar 

  52. Helmrich SP, Ragland DR, 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 

  53. Manson JE, Nathan DM, Krolewski AS. A prospective study of exercise and incidence of diabetes among US male physicians. JAMA 1992; 268: 62–7

    Article  Google Scholar 

  54. Wei M, Gibbons LW, Mitchell TL, et al. The association between cardiorespiratory fitness and impaired fasting glucose and type 2 diabetes in men [published erratum appears in Arch Intern Med 1998; 158 (6): 573]. Ann Intern Med 1999; 130: 89–96

    PubMed  CAS  Google Scholar 

  55. Wei M, Gibbons LW, Kampert JB, et al. Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes. Ann Intern Med 2000; 132: 605–11

    PubMed  CAS  Google Scholar 

  56. Bijnen FC, Caspersen CJ, Feskens EJ, et al. Physical activity and 10-year mortality from cardiovascular diseases and all causes: the Zutphen Elderly Study. Arch Intern Med 1998; 158: 1499–505

    Article  PubMed  CAS  Google Scholar 

  57. Perseghin G, Price TB, Petersen KF, et al. Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects. New Engl J Med 1996; 335(18): 1357–62

    Article  PubMed  CAS  Google Scholar 

  58. Kohrt WM, Spina RJ, Holloszy JO. Prescribing exercize intensity for older women. J Am Geriatr Soc 1998; 46: 129–33

    PubMed  CAS  Google Scholar 

  59. Maggs DG, Buchanan TA, Burant CF, et al. Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. Ann Intern Med 1998; 128: 176–85

    PubMed  CAS  Google Scholar 

  60. Nolan JJ, Ludvik B, Beersden P, et al. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med 1994; 331: 1188–93

    Article  PubMed  CAS  Google Scholar 

  61. Frias JP, Yu JG, Kruszynska YT, et al. Metabolic effects of troglitazone therapy in type 2 diabetic, obese, and lean normal subjects. Diabetes Care 2000; 23: 64–9

    Article  PubMed  CAS  Google Scholar 

  62. Buchanan TA, Xiang AH, Peters RK, et al. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women. Diabetes 2002; 51(9): 2796–803

    Article  PubMed  CAS  Google Scholar 

  63. Cominacini L, Garbin U, Fratta Pasini A, et al. Troglitazone reduces LDL oxidation and lowers plasma E-selectin concentration in NIDDM patients. Diabetes 1998; 47: 130–3

    Article  PubMed  CAS  Google Scholar 

  64. Kruszynska YT, Yu JG, Olefsky JM, et al. Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects. Diabetes 2000; 49: 633–9

    Article  PubMed  CAS  Google Scholar 

  65. Freeman DJ, Norrie J, Sattar N, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001; 103(3): 357–62

    Article  PubMed  CAS  Google Scholar 

  66. Yusuf S, Gerstein H, Hoogwerf B, et al. Ramipril and the development of diabetes. JAMA 2001; 286(15): 1882–5

    Article  PubMed  CAS  Google Scholar 

  67. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157: 2413–46

    Google Scholar 

  68. Curb JD, Pressel SL, Cutler JA, et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension: Systolic Hypertension in the Elderly Program Cooperative Research Group. JAMA 1996; 276(23): 1886–92

    Article  PubMed  CAS  Google Scholar 

  69. Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: metaanalysis of outcome trials. Lancet 2001; 355(9207): 865–72

    Article  Google Scholar 

  70. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360(9346): 1623–30

    Article  PubMed  CAS  Google Scholar 

  71. Sever PS, Dahlöf B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361(9364): 1149–58

    Article  PubMed  CAS  Google Scholar 

  72. Lansberg PJ, Mitchel YB, Shapiro D, et al. Long-term efficacy and tolerability of simvastatin in a large cohort of elderly hypercholesterolemic patients. Atherosclerosis 1995; 116(2): 153–62

    Article  PubMed  CAS  Google Scholar 

  73. Playford DA, Watts GF. Management of lipid disorders in the elderly. Drugs Aging 1997; 10(6): 444–62

    Article  PubMed  CAS  Google Scholar 

  74. LaRosa JC, Applegate WB, Crouse JR. Cholesterol lowering in the elderly: results of the Cholesterol Reduction in Seniors Program (CRISP) pilot study. Arch Intern Med 1994; 154: 529–39

    Article  PubMed  CAS  Google Scholar 

  75. Santanello NC, Barber BL, Applegate WB, et al. Effect of pharmacologic lipid lowering on health-related quality of life in older persons: results from the Cholesterol Reduction in Seniors Program (CRISP) pilot study. J Am Geriatr Soc 1997; 45(1): 8–14

    PubMed  CAS  Google Scholar 

  76. Guyton JR, Blazing MA, Hagar J, et al. Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol: Niaspan-Gemfibrozil Study Group. Arch Intern Med 2000; 160(8): 1177–84

    Article  PubMed  CAS  Google Scholar 

  77. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol: Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341(6): 410–8

    Article  PubMed  CAS  Google Scholar 

  78. Rubins HB, Robins SJ, Collins D, et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med 2002; 162(22): 2597–604

    Article  PubMed  CAS  Google Scholar 

  79. Murdock DK, Murdock AK, Murdock RW, et al. Long-term safety and efficacy of combination gemfibrozil and HMG-CoA reductase inhibitors for the treatment of mixed lipid disorders. Am Heart J 1999; 138(1): 151–5

    Article  PubMed  CAS  Google Scholar 

  80. Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA 2003; 289: 1681–90

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors have no potential conflicts of interest relevant to the contents of this review. Dr Meigs is supported in part by a Career Development Award from the American Diabetes Association.

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  1. The General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 50 Staniford Street, 9th Floor, Boston, Massachusetts, 02114, USA

    Richard W. Grant & James B. Meigs

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Grant, R.W., Meigs, J.B. Should the Insulin Resistance Syndrome be Treated in the Elderly?. Drugs Aging 21, 141–151 (2004). https://doi.org/10.2165/00002512-200421030-00001

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