Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome.

Abstract

Metabolic syndrome shows clustered metabolic abnormalities with major roles for insulin resistance and obesity. Ghrelin is a gastric hormone whose total plasma concentration (T-Ghr) is associated positively with insulin sensitivity and is reduced in obesity. Ghrelin circulates in acylated (A-Ghr) and desacylated (D-Ghr) forms, but their potential differential associations with insulin resistance and whether they are differentially altered in obesity remain undefined. Our objective was to determine potential differential associations of ghrelin forms with insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] and the impact of obesity on their plasma concentrations in metabolic syndrome. This is a cross-sectional study. The study was performed in a metabolic outpatient unit. Patients with metabolic syndrome (National Cholesterol Education Program-Adult Treatment Panel III; n = 45, 23 males/22 females) were included in the study. The main study outcomes were metabolic syndrome criteria, HOMA-IR, and ghrelin forms. Plasma insulin and HOMA-IR were associated negatively with T-Ghr and D-Ghr but positively with A-Ghr and acylated to desacylated ghrelin (A/D-Ghr) ratio (n = 45; P < 0.05). Compared with nonobese [body mass index (BMI) < 27.5 kg/m(2); n = 12, six males/six females], obese metabolic syndrome patients (BMI > 27.5 kg/m(2); n = 33) had lower T-Ghr and D-Ghr but comparable A-Ghr and higher A/D-Ghr ratio (P < 0.05). BMI and waist circumference (WC) were positively related with HOMA-IR (n = 45; P < 0.05). However, opposite associations between A/D-Ghr ratio and HOMA-IR remained significant after adjustment for sex and BMI (or WC). Additional obese individuals without metabolic syndrome (n = 10: age-, sex-, BMI-, and WC-matched to obese metabolic syndrome patients) had lower T-Ghr but higher A-Ghr (P < 0.05) compared with age-, sex-matched healthy nonobese counterparts (n = 15). T-Ghr and A-Ghr were comparable in obese with or without metabolic syndrome. Obesity could alter circulating ghrelin profile, and relative A-Ghr excess could contribute to obesity-associated insulin resistance in metabolic syndrome.