**5. References**

Akishita, M. & Fukai, S. & Hashimoto, M. & Kameyama, Y. & Nomura, K. & Nakamura, T. & Ogawa, S. & Iijima, K. & Eto, M. & Ouchi ,Y. (2010). Association of low

expression of senescence marker protein-30 (SMP30), which was identified as an antioxidant and anti-apoptotic protein, decreased in the proportion of the hepatic fibrosis in NAFLD patients (Park et al., 2010). These results suggest that the association of aging with NASH

There is no specific established treatment for NASH. Management of NASH consists of lifestyle modification including a healthy diet and physical exercise. DHEA has been widely touted as an anti-aging supplement. For years DHEA was promoted as a miracle weight loss drug, based upon some rodent studies that indicated DHEA was effective in controlling obesity in rats and mice. Other rodent studies found similar promising results for DHEA in preventing cancer, arteriosclerosis and diabetes. A randomized, double-blind, placebocontrolled trial showed that DHEA replacement therapy significantly decreases not only in visceral fat area and subcutaneous fat area, but also in insulin resistance. (Villareal & Holloszy, 2004). In contrast, DHEA replacement has no detectable effect on body composition, physical performance, insulin action, or quality of life (Nair et al., 2006). Therapeutic benefits of hormone supplementation for the treatment of aging, insulin resistance and cardiovascular disease remain obscure and controversial. DHEA can cause higher than normal levels of androgens and estrogens in the body, and theoretically may increase the risk of prostate, breast, ovarian, and other hormone-sensitive cancers. A protective effect of DHEA was reported in an orotic acid-induced animal model of fatty liver disease (Goto et al., 1998). Since the clinical usefulness of DHEA for NAFLD patients has never been investigated, there is a

great need for prospective, randomized, multicenter and well-designed trials.

view of anti-aging medicine or endocrinology (Loria et al.,2010).

This study was supported by a Grant from the Chiyoda Mutual Life Foundation.

Akishita, M. & Fukai, S. & Hashimoto, M. & Kameyama, Y. & Nomura, K. & Nakamura, T.

& Ogawa, S. & Iijima, K. & Eto, M. & Ouchi ,Y. (2010). Association of low

Recent studies have demonstrated that more advanced NAFLD, as indicated by the presence of NASH with advanced fibrosis stage, is strongly associated with low circulating DHEA-S. Although NASH patients with severe fibrosis are frequently observed in agedfemale patients, the precise mechanisms of this phenomenon remain to be resolved. Lower levels of serum DHEA in females compared to in males may contribute to the fibrosis progression of NASH. There are thus several potential mechanisms for DHEA deficiency to promote histological progression in NAFLD. DHEA deficiency presents an appealing new therapeutic target for the treatment and prevention of NASH. Since the association of NAFLD with endocrine diseases such as hypothyroidism (Liangpunsakul & Chalasani, 2003), adult growth hormone deficiency (Takahashi et al. 2007), and PCOS (Baranova et al. 2011) has recently been suggested, the pathogenesis of NASH should be explored in the

pathogenesis is noteworthy.

**3. Conclusion** 

**4. Acknowledgment** 

**5. References** 

**2.4 DHEA as a candidate for the treatment of NASH** 

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**6** 

*Japan* 

Hajime Ueshiba

**DHEA and Impaired Glucose Tolerance** 

*Department of Internal Medicine, Toho University School of Medicine, Tokyo,* 

Dehydroepiandrosterone (DHEA) is either secreted directly from the adrenal cortex or is converted from DHEA sulfate (DHEA-S) in the peripheral organs. DHEA and DHEA-S are the most abundant adrenal androgens in blood, however their its physiological roles still remain unclear. Some recent studies have shown that DHEA and DHEA-S exert beneficial effects on conditions such as diabetes mellitus, atherosclerosis, obesity, tumors and osteoporosis (Coleman et al.,1982; Gorden et al.,1988; Cleary,1991). In this chapter, the relationships between DHEA or DHEA-S and diabetes mellitus (DM) or impaired glucose

Abnormalities of secretion and metabolism of many steroid hormones occur in DM. In poorly controlled type 1 DM, serum concentrations of DHEA and DHEA-S decrease (Couch,1992) while plasma ACTH and cortisol levels increase in type 2 DM (Hashimoto et al.,1993). Low levels of DHEA and DHEA-S in type 2 DM are associated with hyperinsulinemia(Hubert et al.,1991; Nesler et al.,1989; Schriock et al.,1988; Smith et al.,1987;). We analyzed serum DHEA and DHEA-S levels in poorly controlled type 2 DM.

The subjects were type 2 diabetic patients seen regularly at the outpatient clinic of Toho University Hospital. We chose 130 patients, whose blood glucose control had been poor (more than 10% in HbA1c). Their medication was managed by diet only or with sulfonylurea, and patients under insulin therapy were excluded. The patient group consisted of 74 men and 56 women between the ages of 40-69yr. Age-matched normal subjects served as the control group. Informed consent was obtained from each subject

Blood samples were obtained from patients with type 2 diabetes mellitus and normal subjects between 9 and 10 a.m. after an overnight fast. From patients with type 2 diabetes mellitus, blood samples were obtained before and 6 months after the treatment. Serum levels of DHEA, DHEA-S and immunoreactive insulin (IRI), fasting plasma glucose (FPG) and HbA1c were measured. Steroid hormones were determined by the previously reported

**1. Introduction** 

tolerance (IGT) are described.

**2. Clinical and basic study** 

**2.1.1 Subjects and methods** 

**2.1 Clinical study** 

before the study.

**Clinical and Basic Study** 

the relationship between serum leptin levels and chronic hyperinsulinemia. *Horm Res,* Vol.63, No.6, pp.270-274.

