Natural History of the Metabolic Syndrome X in Rhesus Monkeys
Barbara Caleen Hansen
University of Maryland School of Medicine, Baltimore, Maryland 22010
Rhesus monkeys (Macaca mulatta) develop many of the aging associated diseases that are seen in humans. We and others have previously described the development of spontaneous type 2 diabetes in adult monkeys. The characteristics of this disease appear to be identical to those of the most common form of type 2 diabetes in humans. Typically this disease becomes apparent in middle age, with a progressively higher prevalence with age. We have identified the actual age onset of type 2 diabetes in monkeys over the age range 10 to 29 years, with the average age of onset being 18.5 years. By onset of diabetes we refer to the observation of two overnight fasted plasma glucose levels of ³126 mg/dl in accord with the most recent ADA recommended classification. This, however, is quite clearly not the beginning of the development of diabetes. In fact many disturbances of metabolism occur prior to overt diabetes. The association of a number of these was noted as long ago as the late 1940s and early 1950s by Jean Vague who focused upon those features which were associated with abdominal obesity. Subsequently in the 1960s a link was made by Welborn and others between obesity, impaired glucose tolerance and cardiovascular risk factors. Reaven in the l980s highlighted the combination of these aging related disorders by referring to them as "Syndrome X". The collection of features that he included were: insulin resistance and impaired glucose tolerance (both part of the prodrome to overt type 2 diabetes), impaired lipid metabolism, and hypertension. Shafrir has referred to these features as "diabesity" in recognition of the importance of obesity to this syndrome. Others have referred to this grouping as the Metabolic Syndrome or the Metabolic Syndrome X, the insulin resistance syndrome, syndrome X plus, the deadly quartet, the plurimetabolic syndrome, trisyndrome metabolique, and the cardiovascular disease risk factor cluster. We have studied this Metabolic Syndrome X in nonhuman primates and shown its 5 major features to be obesity (which appears to consistently precede the others), insulin resistance with hyperinsulinemia, often, but not always associated with the development of obesity, dyslipidemia, which includes hypertriglyceridemia and low HDL cholesterol, impaired glucose tolerance with or without progression to overt diabetes, and hypertension, which occurs with the least consistency and may or may not be a mechanistically related part of the Syndrome. Many other factors have appeared to be associated with the major features of the Metabolic Syndrome X in non human primates and in humans, including blood clotting abnormalities, altered adipose tissue physiology, altered liver function, and increased cardiovascular disease risk.
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