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Recently, two articles published in the BBC news (June 2006 and September 2007), have focused the public attention on RBP4 testing. Indeed, the two BBC news articles discussed the evidence existing in the literature for this Biomarker and introduced RBP4 as an �Early warning hope for diabetes� and a �Test that measures fat around organs�. This text is devoted to RBP4 and its link with obesity and diabetes.
Industrialized and developing countries are characterized by a marked increase in people presenting with diabetes, obesity, metabolic syndrome and hypertension. These disorders are associated with adverse cardiovascular events such as heart disease, stroke and peripheral vascular diseases. The worldwide rise of obesity and diabetes reflects a significant change in diet habits, physical activity levels, and tobacco consumption. It also results from industrialization, urbanization, economic development and food market globalization. Individuals are simultaneously consuming an energy-denser and nutrient-poorer diet as well as being less physically active.
Retinol binding protein 4 (RBP4) is the vitamin A-transport protein secreted into the circulation by adipocytes and is perceived as an adipocyte-derived signal that may contribute to the pathogenesis of type 2 diabetes .
The build-up of visceral fat has been linked to an increased risk for heart disease and type-2 diabetes. RBP4 has recently been correlated to the level of visceral fat and a link between obesity and insulin resistance.
Indeed, a 2 to 3-fold increase in serum RBP4 in obese subjects was positively correlated with abdominal fat mass and inversely with insulin sensitivity, independently of age, gender and body mass index . Furthermore, in 102 healthy women, serum RBP4 levels were independently associated with visceral fat and LDL-cholesterol levels .
This observation was confirmed in different populations, as illustrated by Qi et al. (4) who have measured RBP4 plasma levels in 3289 Chinese individuals, aged from 50 to 70 years, and demonstrated a strong and independent association with metabolic syndrome. This association in the Chinese population was confirmed by another group.
RBP4 is also described in the literature as a good risk estimate of insulin resistance and diabetes. Cho et al. (6) have reported that plasma RBP4 concentrations were elevated in subjects with impaired glucose tolerance or type 2 diabetes and Graham et al. (7) have demonstrated that serum RBP4 levels correlated with the magnitude of insulin resistance in subject with obesity, impaired glusoce tolerance, or type-2 diabetes, and in non-obese, non-diabetic subjects. Moreover, Takebayashi et al. (8) have reported that RBP4 is associated with variables related to insulin resistance and diabetic complications (triglycerides, systolic blood pressure, urinary albumin and low HDL cholesterol. These observations are completed by the study of Craig et al. (9) who have shown that SNPs -804 and +9476 in the RBP4 gene were associated with reduced insulin secretion and while SNP +390 was linked to reduced insulin sensitivity.
Over-secretion of RBP4 may negatively affect beta-cell function directly or indirectly by preventing the binding of transthyretin to its receptor. These mechanisms could explain, at least parly, the association between increased circulating RBP4 and type-2 diabetes .
Therefore, these data provide a rationale for antidiabetic therapies aimed at lowering serum RBP4 levels and hence at reducing the risk of full-blown disease. This therapeutic perspective was recently illustrated by Haider et al. (11) who have shown that rosiglitazone reduced RBP4 in HIV-positive subjects thereby contributing to the pharmacodynamic action of thiazolinediones on glusoce homeostasis.
Presently, RBP4 is essentially measured by radioimmunoassay or ELISA, which are time consuming. The recent evidence for its importance in the pathogenesis of type-2 diabetes warrants the promotion for a fully and friendly automated assay that would allow an easier and wider use of this biomarker.
In summary, as RBP4 may prove to be a reliable estimate of the amount of visceral fat and a marker for identifying individuals at risk of diabetes before symptoms become apparent, its measurement could provide an opportunity for patients to take preventive measures and could contribute to public health benefits.
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