Plasma Ghrelin and Insulin Resistance in Non-Diabetic Adults with Obesity: A Scoping Review of Current Evidence

Abstract

Obesity is heterogeneous, and ghrelin could be useful for distinguishing insulin-sensitive from insulin-resistant phenotypes beyond body mass index. This review aimed to map the evidence on total ghrelin, acylated ghrelin, des-acylated ghrelin, the acy/des-acy ghrelin ratio, and the relationships of these variables with insulin resistance/sensitivity in obesity-related groups. The evidence, based on the Population–Concept–Context framework, was categorised according to the Joanna Briggs Institute (JBI) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. The synthesis was conducted by ghrelin phenotype, sampling condition, assay method, metabolic measure, and direction of association. A total of 18 duplicate citations were discarded, and 93 distinct sources were mapped (including 37 human or clinical sources, 34 contextual sources, 16 methodological sources, and 6 mechanistic studies) from 94 screened sources. Total ghrelin was the most frequently evaluated exposure, while the Homeostatic Model Assessment of Insulin Resistance and fasting insulin were the predominant metabolic measures. A reduction in total ghrelin was associated with hyperinsulinemia, increased HOMA-IR, abdominal obesity, metabolic syndrome, and metabolically unhealthy obesity. However, not all studies on acylated ghrelin were consistent. In some studies, acylated ghrelin was lower in obese people, while in others, a higher ratio of acylated ghrelin to des-acylated or unacylated ghrelin correlated with reduced insulin sensitivity. There was a restriction on interpretation due to cross-sectional designs, small sample sizes, heterogeneous definitions of phenotype, fasting-only assessments, inconsistent sample stabilisation, different assay platforms, and the absence of clamp-derived insulin sensitivity in the core evidence. A low total circulating ghrelin level was the most consistent among those associated with insulin-resistant obesity, while the molecular form ratios may convey additional metabolic information.