Age yr

FIG. 1. Effect of age on fasting and 2 h plasma glucose levels in men from the Baltimore Longitudinal Study of Aging.

glucose tolerance (Andres 1971, Broughton & Taylor 1991, Davidson 1979, DeFronzo 1981, Reaven et al 1989). Oral glucose tolerance tests (OGTTs), conducted in healthy non-diabetic individuals across the age range clearly demonstrate a decline in glucose tolerance, as judged from the fasting, intermediate and the 2 h levels, in each age decade from the third decade (20—29 year old) to the ninth decade (80—89 year old) (Elahi & Muller 2000). This decline is easily appreciated from the relationship of age and either fasting or 2 h level, as shown in Fig. 1, and is observed both in men and women. The two-hour plasma glucose level during an OGTT rises on average, 5.3 mg/dl per decade and the fasting plasma glucose rises on average, 1 mg/dl per decade (Davidson 1979). The decline in glucose tolerance is also reflected in NHANES III survey on the prevalence of diabetes and impaired fasting glucose and impaired glucose tolerance in US adults (Harris et al 1998). Comparison of the percentage of physician-diagnosed diabetes in middle-aged adults (40—49 years) and elderly adults (575 years) reveals an increase from 3.9% to 13.2%. The percentage of adults with (a) undiagnosed diabetes (fasting plasma glucose [FPG] 5 126 mg/dl) increased from 2.5 to 5.7%; and (b) impaired FPG (110—125 mg/dl) increased from 7.1% to 14.1%. Thus, approximately a third of the elderly adults in the USA have abnormal glucose metabolism as defined by the revised 1997 criteria of the American Diabetes Association (The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 1997). A detailed review of the effects of ageing on glucose homeostasis, in both humans and animals, has recently been

Body mposition

Blood Pressure

Activi (Fitne:



FIG. 2. Risk factors of the metabolic syndrome. Each line represents a statistically significant association between each risk factor that is found in most populations.

Fat Distribution


Glucose Tolerance

FIG. 2. Risk factors of the metabolic syndrome. Each line represents a statistically significant association between each risk factor that is found in most populations.

published in a number of relevant articles (Evans & Farrell 2001). The reduction of glucose tolerance associated with ageing is also accompanied with dyslipidaemia and hypertension. The clustering of these conditions is commonly referred to as syndrome X or the metabolic syndrome. These pathological conditions are more prevalent in the elderly and are complex, interrelated and multifunctional. The complexity of these inter-relationships is depicted in Fig. 2. The lines connecting the different factors represent the statistically significant associations that exist in the cross-sectional analysis of most populations. For example, a significant decrease in glucose tolerance with increasing age can be demonstrated from all epidemiological studies. However, this relationship is confounded by an increase in adiposity and a decrease in physical activity with age and each of these factors are also associated with a decrease in glucose tolerance. It is difficult to demonstrate how much of the glucose intolerance can be attributed solely to ageing, decreased activity or increased adiposity; the combination of these certainly leads to glucose intolerance. Similarly, the relationships of age, hyperinsulinaemia, dyslipidaemia and insulin resistance are interwoven. This review focuses on the clinical evidence of a change with age in insulin resistance and insulin secretion that is independent of changes in other known factors.

Shimokata et al (1991) examined the relationship between age, obesity, physical activity and glucose tolerance in a community dwelling with men and women ranging in age from 17 to 92, from the Baltimore Longitudinal Study of Aging (BLSA). The independent effect of age on glucose tolerance was examined after statistical adjustment for the confounding effects of obesity, fat distribution and physical activity. They found that the decline in glucose tolerance from early adult (17—39 year) to middle age (40-59 year) is entirely explained by the secondary influences of fatness and fitness. However, the decline from mid-life to old age (60-92 year) was still influenced by chronological age. Other population studies also attribute the decline in glucose tolerance to age-related environmental factors (obesity, physical activity, dietary habits, diabetogenic drug use) (Zavaroni et al 1986, Maneatis et al 1982, Zamboni et al 1997). However, it should be noted that anthropometric determination of body composition and questionnaire-derived assessment of impaired activity have their limitations. Furthermore, when statistical adjustment is made, in addition to the variability in the precision of the measured confounders, linear relationships between the confounders are assumed, interactions between them are ignored, and sample size may not be sufficiently large. Thus, in a complex statistical model, true cause—effect relationships may not be detectable due to under/over adjustment or imprecision.

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