الفهرس 
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Abstract
Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion as in type1 diabetes mellitus, or resistance to insulin action or both as in type 2 diabetes mellitus. Diabetes mellitus has a high mortality rate due to its complications. Most diabetic complications arise from damage to blood vessels that affect either small blood vessels (microvascular complications) or large blood vessels (macrovascular complications). Diabetic nephropathy is considered as the most common and serious microvascular complication which leads to end-stage renal disease. It is recorded in approximately one third of patients with diabetes.
Obesity is a disease in which excess body fat has accumulated to such an extent that health may be negatively affected. It is commonly defined as a body mass index (weight divided by height squared) of 30 kg/m2 or higher. Many studies show an association between excessive body weight and various diseases, particularly type 2 diabetes mellitus. Besides lipid accumulation and free fatty acids (FFA) release, adipocytes together with other adipose tissue cells produce and release multiple signaling proteins termed adipokines. RBP4 was recently discussed as a new adipokine that could be linked to obesity and impaired glucose metabolism.
In order to study the association between serum levels of retinol-binding protein 4 (RBP4) and the presence of obesity and type 2 diabetes mellitus, as well as its evaluation as a risk factor for diabetic nephropathy, serum levels of RBP4 were measured in forty adult diabetic patients (fifteen lean diabetic patients and twenty-five obese diabetic patients); twenty adult obese non- diabetic patients and fifteen apparently healthy age - and sex-matched subjects serving as a control group. Diabetic patients were additionally classified according to their albumin/ creatinine ratio into sixteen diabetic normoalbuminuric patients, thirteen diabetic microalbuminuric patients and eleven diabetic macroalbuminuric patients. Assay of serum RBP4 was carried out using an enzyme-linked immunosorbent assay (ELISA) technique.
The results of the present study showed a highly significant increase in serum RBP4 levels in obese non-diabetic subjects when compared to the healthy control group. Furthermore, elevated serum RBP4 levels were positively correlated with markers of central obesity (BMI, waist circumference and waist-to-hip ratio); as well as lipid profile parameters (total cholesterol, TG). Also, a significant increase in BUN, creatinine and albumin/creatinine ratio with a highly significant decrease in eGFR was observed in obese non-diabetic patients.
As regards serum RBP4 levels in the studied diabetics, a highly significant increase was recorded in obese diabetics as compared to the healthy control group as well as the lean diabetic group, this being associated with a highly significant increase in total cholesterol, LDL-C and TG levels with low HDL-C levels.
Serum RBP4 levels in obese diabetic patients were higher than those in the obese non-diabetic group, but the difference between the two groups was not statistically significant. Also, there was a significant positive correlation between serum RBP4, BMI and waist-to-hip ratio in obese non-diabetic patients together with absence of a statistically significant correlation with fasting plasma glucose and HbA1c levels in the same group. This reflects the role of the adipose tissue as an important source of circulating RBP4 even in absence of hyperglycemia.
As regards the relation between RBP4 and diabetic nephropathy, serum RBP4 levels showed a highly significant increase in both micro- and macroalbuminuric diabetic patients as compared to healthy control subjects. Furthermore, serum levels of the marker were significantly higher in the macroalbuminuric subgroup.
When ROC curve analysis was applied to serum RBP4 in obese diabetic patients versus obese non-diabetic ones, this revealed that the best diagnostic cut-off level of the marker was 1.40 µg/mL (diagnostic sensitivity 72%, specificity 55%, positive predictive value 67%, negative predictive value 61%, and diagnostic efficacy 64%). The overall performance of the marker was relatively poor as judged by an AUC of 0.659 only.
Assessment of diagnostic performance of serum RBP4 in obese diabetic patients versus lean diabetic ones using ROC curve analysis revealed that the best diagnostic cut-off level of serum RBP4 was 1.14 µg/mL. This had a diagnostic sensitivity of 76%, specificity 73%, positive predictive value 83%, negative predictive value 65%, and a diagnostic efficacy of 75%, with an AUC of 0.741.
The remarkable observation in the present study was the excellent diagnostic performance of serum RBP4 in diabetic microalbuminuric patients versus diabetic normoalbuminuric ones, where the AUC approached 1.0 (0.983). The best diagnostic cut-off level of the marker was 1.10 µg/mL. This had a diagnostic sensitivity of 100%, diagnostic specificity 94%, positive predictive value 93%, negative predictive value 100%, and 97% diagnostic efficacy.