The metabolic syndrome is characterized by visceral obesity, insulin resistance, Type 2 diabetes, dyslipidemia
and hypertension. These risk factors and diseases are also associated with cortisol hyperactivity, such as in Cushing’s syndrome.
Therefore, increased cortisol activity may be considered to be a pathogenetic mechanism also for the metabolic
syndrome, despite cortisol levels within reference values. In one study thirty women, 49-65 yrs old, with visceral obesity,
insulin resistance and Type 2 diabetes were treated with ketoconazole 400 mg daily, in order to down-regulate cortisol activity,
in a 3-month randomized, double-blind, placebo-controlled trial. In another study, a modified release formulation of
ketoconazole was administered to 72 men and women in a 3-month randomized, double-blind, placebo-controlled trial at
three different centers. In a third study, an enantiomer of ketoconazole was evaluated in 36 patients with Type 2 diabetes
who were studied for 14 days. All three studies demonstrated that a down-regulation of cortisol secretion can favorably affect
most of the multiple risk factors associated with the metabolic syndrome such as improvements in insulin resistance,
glucose homeostasis, total cholesterol, blood pressure and hepatic steatosis. The last study also indicated a decrease in
CRP, which has been reported to be elevated in metabolic syndrome/insulin resistance.