The Role of Cortisol in the Pathogenesis of the Metabolic Syndrome

Abstract

Corresponding author: In-Kyung Jeong Division of Endocrinology & Metabolism, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, 892 Dongnam-ro, Gangdong-gu, Seoul 134-727, Korea E-mail: jik1016@dreamwiz.com Metabolic syndrome (MetS) is a constellation of metabolic derangements that includes insulin resistance, hyperglycemia, hypertension, reduced high density lipoprotein cholesterol (HDL-C), elevated triglycerides, and abdominal obesity. It was originally described by Reaven in 1988 as “syndrome X” or “insulin resistance syndrome” [1]. MetS increases the risk for development of type 2 diabetes mellitus as well as cardiovascular disease [2]. The prevalence of MetS has increased worldwide, with an increase from 19.6% in 1998 to 32.4% in 2009, according to the Korean National Health and Nutrition Examination Survey (NHANES) [3]. In spite of the increasing prevalence of MetS, there are no uniformly accepted diagnostic criteria for MetS. Different organizations have suggested their own criteria. The National Cholesterol Education Program (NCEP) Adult Treatment Panel-III (ATP III) guidelines [4] are the most widely used, and require at least three of the following: 1) central obesity (waist circumference ≥90 cm for Asian men or ≥80 cm for Asian women, 2) triglycerides ≥150 mg/dL, or receiving drug treatment for high triglycerides, 3) HDL-C <40 mg/dL for men or <50 mg/dL for women or receiving drug treatment for low HDL-C, 4) systolic/diastolic blood pressure ≥130/85 mm Hg or receiving drug treatment for high blood pressure, and 5) fasting plasma glucose ≥100 mg/dL or receiving drug treatment for high fasting plasma glucose levels. However, according to the International Diabetes Federation (IDF) criteria [5], abdominal obesity (waist circumference ≥90 cm for Asian men or ≥80 cm for Asian women) is a prerequisite for the diagnosis of MetS, in addition to at least two of the following components: 1) triglycerides ≥150 mg/dL or receiving drug treatment for high triglycerides, 2) HDL-C <40 mg/dL for men or <50 mg/dL for women or receiving drug treatment for low HDL-C, 3) systolic/diastolic blood pressure ≥130/85 mm Hg or receiving drug treatment for high blood pressure, and 4) fasting plasma glucose ≥100 mg/dL or receiving drug treatment for high fasting plasma glucose levels. Yoon et al. [6] compared the two criteria. All MetS patients who met the IDF criteria also met the revised NCEP criteria. Patients who met the NCEP criteria but not the IDF criteria were metabolically obese with normal waist circumferences and significantly worse metabolic profiles than the MetS-free group. This illustrates why the revised NCEP criteria are preferred to the IDF criteria for measuring the prevalence of MetS in Korea. Even though the primary mechanism of MetS is insulin resistance, there is still controversy regarding the pathogenesis of MetS. Because the clinical features of MetS are shared by Cushing’s syndrome (CS), mild hypercortisolism was proposed as one of the pathogenic mechanisms of MetS [7]. Shared features between MetS and CS are abdominal obesity, high triglycerides, low HDL-C, hypertension, and hyperglycemia. Previous studies have evaluated the association between MetS and hypercortisolism by examining fasting plasma cortisol, 24-hour urinary free cortisol, cortisol reactivity to some stimuli, or profiles of cortisol patterns over the day [8-24]. More Editorial Obesity and Metabolic Syndrome