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Objective. The retinol-binding protein 4 (RBP4) has been linked to the insulin resistance state in obesity and type 2 diabetes in animal studies. Data in humans are controversial and their relationship with organ damage in diabetic patients is lacking. We studied the association of plasma RBP4 with organ complications in type 2 diabetic patients.Setting. Sant Joan University Hospital, Reus, Spain.Subjects. 165 nonsmoker type 2 diabetic subjects according to American Diabetes Association criteria, aged 36-79 years, without proteinuria or severely decreased glomerular filtration rates (MDRD-GFR <30 mL min )1 1.73 m )2 ), were included in the study.Main outcome measure. Plasma RBP4 concentrations were the primary outcome variable. Statistics were performed in relation to clinical and subclinical arteriosclerosis, renal function parameters and biochemical data.Results. Plasma RBP4 concentrations were positively correlated with serum creatinine levels (r = 0.322, P < 0.001) and inversely correlated with MDRD-GFR (r = )0.468, P = 0.009). Patients with moderately renal dysfunction (MDRD-GFR <60 mL min )11.73 m )2 ) had higher plasma RBP4 concentrations than those with normal to mildly decreased GFR (55.3 ± 24.6 vs. 40.8 ± 15.4, P < 0.001). Patients in the top quartile of RBP4 concentrations had an increased adjusted odds ratio for moderately renal dysfunction compared with lower quartiles (4.68; 95% CI: 1.52-14.36, P = 0.007). The presence of microalbuminuria was not associated with RBP4. Plasma RBP4 concentrations were higher in those subjects with previous clinical arteriosclerosis than in event-free subjects (48.8 ± 24.2 vs. 40.6 ± 13.9, P = 0.045). The presence of retinopathy or polyneuropathy did not differ across RBP4 quartiles.Conclusions. Plasma RBP4 concentration might be a biomarker of nephropathy and cardiovascular disease in type 2 diabetic subjects.

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The aim of this study was to evaluate the impact of adipocyte fatty acid binding protein 4 (FABP4) on the lipid profile in type 2 diabetic subjects. Plasma levels of FABP4 and adiponectin and an extensive lipid profile were analyzed in 169 type 2 diabetic subjects and 105 controls. Type 2 diabetic subjects were categorized according the presence of atherogenic dyslipidemia. Univariate statistical analyses, partial correlation tests, and binary logistic regression models were applied. In type 2 diabetic subjects, FABP4 was positively correlated with plasma triglycerides (P 5 0.007), apolipoprotein C-III (apoC-III) (P 5 0.009), and all the components of triglyceride-rich lipoproteins, including VLDL triglycerides (P 5 0.002), VLDL-cholesterol (P 5 0.001), and VLDL apoB (P 5 0.001). FABP4 was inversely correlated with apoA-I (P 5 0.038), HDL-cholesterol (P 5 0.002), and HDL apoA-I (P 5 0.010) in type 2 diabetic subjects. These correlations are not significantly affected by age, gender, body mass index, adiponectin, insulin, or any pharmacological treatment. The associations are even stronger when the FABP4/adiponectin ratio is considered. None of these associations were observed in controls. High FABP4 and low adiponectin levels are independent predictors of atherogenic dyslipidemia. In conclusion, FABP4 plasma concentrations hold strong potential for development as a clinical biomarker for atherogenic dyslipidemia, independent of obesity and insulin resistance, in type 2 diabetic subjects.-Cabré, A., I. Lázaro, J. Girona, J. M. Manzanares, F. Marimón, N. Plana, M. Heras, and L. Masana. Plasma fatty acid binding protein 4 is associated with atherogenic dyslipidemia in diabetes. J. Lipid Res.

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Background: Glucose-regulated protein 78/Binding immunoglobulin protein (GRP78/BiP) is a protein associated with endoplasmic reticulum stress and is upregulated by metabolic alterations at the tissue-level, such as hypoxia or glucose deprivation, and it is hyper-expressed in fat tissue of obese individuals. Objective: To investigate the role of the GRP78/BiP level as a metabolic and vascular disease biomarker in patients with type 2 diabetes (DM), obesity and metabolic syndrome (MS). Methods: Four hundred and five patients were recruited, of whom 52.5% were obese, 72.8% had DM, and 78.6% had MS. The intimae media thickness (cIMT) was assessed by ultrasonography. The plasma GRP78/BiP concentration was determined, and its association with metabolic and vascular parameters was assessed. Circulating GRP78/BiP was also prospectively measured in 30 DM patients before and after fenofibrate/niacin treatment and 30 healthy controls. Results: In the cross-sectional study, the GRP78/BiP level was significantly higher in the patients with obesity, DM, and MS. Age-, gender- and BMI-adjusted GRP78/BiP was directly associated with LDL-cholesterol, non-HDL-cholesterol, triglycerides, apoB, and cIMT. GRP78/BiP was positively associated to carotid plaque presence in the adjusted model, irrespective of obesity, DM and MS. In the prospective study, nicotinic acid treatment produced a significant reduction in the GRP78/BiP levels that was not observed with fenofibrate. Conclusions: GRP78/BiP plasma concentrations are increased in patients with both metabolic derangements and subclinical atherosclerosis. GRP78/BiP could be a useful marker of metabolic and cardiovascular risk.

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