**2.2 The significance of serum DHEA-S levels**

Whereas DHEA levels naturally reach their peak in the early morning hours, DHEAS levels show no diurnal variation. From a practical point of view, measurement of DHEAS is preferable to DHEA, as levels are more stable. The Baltimore Longitudinal Study of Aging (BLSA) is a multidisciplinary observational study of the physiological and psychological aspects of human aging and diseases and conditions that increase with age. In BLSA, men who had higher DHEAS levels had significantly greater longevity than men with lower levels. (Roth et al., 2002) In Japan, a 27-year study in a community-based cohort (Tanushimaru study) indicated that DHEAS level may be a predictor of longevity in men, independent of age, blood pressure, and plasma glucose (Enomoto et al, 2008). Low serum levels of DHEA(-S) predict death from all causes, cardiovascular disease, and ischemic heart disease in elderly Swedish men. (Ohlsson et al., 2010) On the basis of these results, serum DHEA level is known to be an indicator of longevity at least in men and is often determined in anti-aging checkups (Nishizaki et al., 2009) . Elevated levels of DHEA are found in patients with Cushing syndrome or congenital adrenal hyperplasia, while DHEA levels are reported to be low in some people with anorexia, end-stage kidney disease, type 2 diabetes, AIDS, adrenal insufficiency, and in the critically ill. Some studies suggested that low serum DHEA-S levels were associated with the metabolic syndrome (Muller et al., 2005, Chen et al., 2010). In contrast, several studies found that DHEA levels are not different between subjects with metabolic syndrome and without. (Fukui et al., 2007, Haring et al., 2009, Akishita et al., 2010) It is suggested that age per se is an important correlate of the associations between DHEA-S and metabolic variables. In this way, the previous studies regarding the association between endogenous DHEA-S level and metabolic syndrome are inconsistent. Previous studies have shown that diabetic patients with high serum levels of insulin have lower serum levels of DHEA and DHEA-S. (Yamaguchi et al., 1998). A negative correlation between DHEA and hyperinsulinemia has been repeatedly demonstrated. (Kauffman et al., 2006, Saygili et al., 2005, Vasarhelyi et al., 2003). Fukui and colleagues reported that low levels of DHEA are associated with atherosclerosis and deterioration of urinary albumin excretion in male patients with type 2 diabetes (Fukui et al., 2004, 2005, 2006). Similarly, Serum DHEA-S level seem to be associated with atherosclerosis in diabetic postmenopausal women independent of age, body stature, diabetic status, and other atherosclerotic risk factors (Kanazawa et al., 2008).
