New blood test for diabetes

Type 2 diabetes mellitus is the scourge of the Westernised world. Humans evolved for tens of thousands of years to be semi-starved. Our physiology has yet to adapt to the veritable glut of high calorie food available to humans in the industrialised world.

Diabetes has traditionally been diagnosed on higher than normal fasting blood sugar levels. However, where the sugar is not very high, an oral glucose tolerance test is often needed – which involves at least two blood tests separated by a couple of hours. Even with this test, there is a proportion of patients with a “normal” test who are at risk or prone to developing diabetes.

Fasting insulin assays can be performed but they can be inaccurate.

Kahn and colleagues at the Beth Israel Deaconess Medical Center in Boston have discovered a new marker for diabetes. The level of “retinol-binding protein 4” (RBP4) seems to be highly correlated with the degree of insulin resistance.

Although it is early days, this test may become highly significant for screening for diabetes and pre-diabetes in the future; being more reliable and convenient than a fasting blood sugar and then oral glucose tolerance test.

Reference article
Graham TE., Yang Q., Blüher M., et al. Retinol-Binding Protein 4 and Insulin Resistance in Lean, Obese, and Diabetic Subjects. NEJM Volume 354(24):2552-2563, June 15, 2006

ABSTRACT
Background
Insulin resistance has a causal role in type 2 diabetes. Serum levels of retinol-binding protein 4 (RBP4), a protein secreted by adipocytes, are increased in insulin-resistant states. Experiments in mice suggest that elevated RBP4 levels cause insulin resistance. We sought to determine whether serum RBP4 levels correlate with insulin resistance and change after an intervention that improves insulin sensitivity. We also determined whether elevated serum RBP4 levels are associated with reduced expression of glucose transporter 4 (GLUT4) in adipocytes, an early pathological feature of insulin resistance.

Methods
We measured serum RBP4, insulin resistance, and components of the metabolic syndrome in three groups of subjects. Measurements were repeated after exercise training in one group. GLUT4 protein was measured in isolated adipocytes.

Results
Serum RBP4 levels correlated with the magnitude of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body-mass index, waist-to-hip ratio, serum triglyceride levels, and systolic blood pressure and decreased high-density lipoprotein cholesterol levels. Exercise training was associated with a reduction in serum RBP4 levels only in subjects in whom insulin resistance improved. Adipocyte GLUT4 protein and serum RBP4 levels were inversely correlated.

Conclusions
RBP4 is an adipocyte-secreted molecule that is elevated in the serum before the development of frank diabetes and appears to identify insulin resistance and associated cardiovascular risk factors in subjects with varied clinical presentations. These findings provide a rationale for antidiabetic therapies aimed at lowering serum RBP4 levels.