Endocrine Abstracts

Background: Secretory products from adipocytes may contribute to increased insulin resistance (IR). Retinol-binding protein-4 (RBP-4) may increase IR in mice, with elevated levels in insulin resistant mice and humans with obesity and type 2 diabetes. Mechanisms regulating RBP-4 synthesis remain not fully understood. It is not clear whether short-term hyperglycaemia alters RBP-4 levels in humans. In order to investigate this, we measured serum RBP-4 concentrations during 75 gram oral glucose tolerance test (OGTT).

Subjects and methods: The study included 24 subjects (5 males), age 38.7±15.1 years, BMI 34.4±8.3 kg/m². Glucose, insulin and RBP-4 were measured at 0, 60 and 120 min of OGTT. IR was assessed by HOMA (calculated as fasting insulin (μU/ml)×fasting glucose (mmol/l)/22.5) and by Insulin Resistance Index (IRI) that takes into account glucose and insulin levels during OGTT. IRI is calculated through the formula: 2/(1/(INSp×GLYp))+1, where INSp and GLYp are the measured insulin and glycaemic areas.

Results: Glucose administration resulted in significant increases in insulin and glucose (P<0.0001). There was, however, no change in RBP-4 concentrations (124.1±32 μg/ml at 0 min, 123±35 μg/ml at 60 min and 126.5±37.5 μg/ml at 120 min of OGTT, P=ns). RBP-4 correlated moderately with fasting insulin (r=0.40, P=0.025), fasting glucose (r=0.41, P=0.02) and HOMA (r=0.43, P=0.015), but not with IRI (r=0.19, P=0.31). There was, however, only a moderate correlation between HOMA and IRI (r²=0.24; P=0.006) (Spearman rank correlation), while the best correlation was obtained between the product of glucose and insulin levels at 60 min of OGTT and IRI in a non-linear model (r²=0.88; P<0.00001).

Conclusions: RBP-4 levels do not change during oral glucose tolerance test, so it is unlikely that RBP-4 is involved in short-term regulation of glucose homeostasis. Moderate correlation between RBP-4 and HOMA suggests, however, that RBP-4 may be one of many factors that influence insulin sensitivity in humans. Lack of correlation between RBP-4 and IRI may be a consequence of a limited correlation between static (HOMA) and dynamic indices of insulin resistance (IRI).