Should the insulin resistance syndrome be treated in the elderly?

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 greater than or equal to60. 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. Cardiovascular disease (CVD) is the leading cause of death among people >65 years of age in developed countries([1]) The insulin resistance syndrome (defined as the co-occurrence of hyperglycaemia, hypertension, obesity [both central and overall], elevated levels of triglycerides and low levels of high density lipoprotein-cholesterol [HDL-C]) may play an important role in the development of type 2 diabetes mellitus and CVD.([2,3]) Thus, recognition and appropriate treatment of this syndrome is critical for the effective care of older patients. In this article, we review the pathophysiology and epidemiology of the insulin resistance syndrome and present the evidence for treatment among the elderly, defined as patients >65 years of age. Both peripheral insulin resistance and failure of pancreatic cells to produce enough insulin to overcome peripheral insulin resistance precede the development of type 2 diabetes([4]) Insulin resistance also predicts the development of hypertension and low HDL-C/high triglycerides dyslipidaemia characteristic of diabetes. Thus, insulin resistance constitutes the central element of the insulin resistance syndrome (also called syndrome X or the metabolic syndrome)([5]) Over the past two decades, the prevalence of diabetes has increased dramatically; among US adults aged 40-74 years the prevalence increased from 8.9% to 12.3% by 1994.([6]) This figure is even higher among older adults. During 1988-1994, 13.2% of adults >74 years of age had physician-diagnosed diabetes; these figures are doubled if undiagnosed diabetes is included.([6]) Among people destined to develop diabetes, the prevalence of CVD risk factors is greatest in the most insulin-resistant subjects compared with relatively insulin-sensitive subjects([7-10]) These multiple risk factors confer independent, additive risk with diabetes for CVD-related mortality([11]) Long-time exposure to the risk factors present in the insulin resistance syndrome is an important determinant for developing CVD complications in the elderly.([12])