Context: 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 remains undefined.

Objective: To determine potential differential associations of ghrelin forms with insulin resistance (HOMA-IR) and impact of obesity on their plasma concentrations in metabolic syndrome.

Design: Cross-sectional

Setting: Metabolic outpatient unit

Patients: Metabolic syndrome (NCEP-ATP III, n=45, 23M/22F).

Main Outcomes: Metabolic syndrome criteria, HOMA-IR, ghrelin forms.

Results: Plasma insulin and HOMA-IR were associated negatively with T- and D-Ghr but positively with A- and A/D-Ghr ratio (n=45; P<0.05). Compared to non-obese (BMI<27.5 kg/m²; n=12,6M/6F), obese metabolic syndrome patients (BMI>27.5; n=33) had lower T- and D-Ghr but comparable A- and higher A/D-Ghr (P<0.05). BMI and waist circumference (WC) were positively related with HOMA-IR (n=45; P<0.05). Opposite associations between A/D-Ghr and HOMA-IR remained however 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- but higher A-Ghr (P<0.05) compared to age-, sex-matched healthy non-obese counterparts (n=15). T- and A-Ghr were comparable in obese with or without metabolic syndrome.

Conclusions: Obesity could alter circulating ghrelin profile, and relative A-Ghr excess could contribute to obesity-associated insulin resistance in metabolic syndrome.