Association Of Retinol-binding Protein 4 Research Articles

Sexual Dimorphism in the Association of Serum Retinol-Binding Protein-4 With Long-Term Dynamic Metabolic Profiles in Non-Diabetes.

ObjectivesWe aimed to investigate the association of circulating retinol-binding protein-4 (RBP4) levels with long-term cardiometabolic risk profiles and whether sex disparity mattered.MethodsWe included 784 non-diabetic participants aged 40 years and above from a well-defined community-based cohort at baseline in 2005 and they were invited to attend the on-site follow-up examination for two consecutive times with 3-year intervals in 2008 and 2011, respectively. Serum RBP4 was measured at baseline, and the anthropometry and biochemical measurements were performed at each visit. Generalized estimating equation models were used to assess the association of serum RBP4 levels with the dynamic changes in adiposity and glucolipid profile.ResultsBased on all the baseline and the 3- and 6-year follow-up data, baseline serum RBP4 levels (each 1-unit of log10RBP4) were significantly associated with waist circumference [β=3.12, 95% confidence interval (CI) (0.77, 5.47), P=0.01], fasting, and 2-h post-loading glucose [β=0.26 (0.05, 0.47), P=0.02, and 1.70 (1.29, 2.12), P< 0.0001], serum triglycerides [β=0.75, 95% CI (0.54, 0.96), P< 0.0001], total cholesterol [β=0.47, 95% CI [0.23 0.70], P<0.0001), and marginally with body mass index (β=0.97, 95% CI (0.02, 1.93), P=0.046], in total participants, after adjusting potential confounders. The association of RBP4 with 2-h post-loading glucose was stronger in women than that in men [β=1.99, 95% CI (1.49, 2.50) vs. 0.61 (-0.14, 1.36), P for interaction=0.001]. The analysis of change in Z-score of cardiometabolic profiles corresponding to each 1-unit increment in log10RBP4 showed consistent results.ConclusionsHigher RBP4 levels are associated with longitudinal increase in adiposity and deteriorated glucolipid profile defined by repeated measurements. The associations differ in sex regarding to the 2-h post-loading glucose.

Association of Retinol Binding Protein-4 and Microalbuminuria and Blood Glucose Regulation in Type 2 Diabetic Iraqi Patients

Retinol binding protein 4 (RBP-4) has long been known as the carriers for vitamin A, in the plasma it is banded to transthyretin to form too large complex for glomerulus filtration. Discovered as adipokine involved in the pathogenesis of type 2 diabetes induced insulin resistant and linked to obesity. Diabetic nephropathy one of serious microvascular complication that impact large numbers of the patient however, association with RBP-4 is not fully known. The present study tested this hypothesis by measuring serum RBP4 in samples of Iraqi type 2 diabetic (n=120) with normal albumin excretion (n=57) and microalbuminuria (n=63) of either sex. and Also apparently health subjects (n=30) were involved to serve as control. Concentrations of the RBP4 were significantly elevated in serum of microalbuminuric diabetic patients as compare with normoalbuminuric patients, (p=0.000&lt;0.05). also glycemic index parameters significantly higher (for all p&lt;0.05). In conclusion, the study suggested that serum level of RBP4 are affected by microalbuminuria and the assessment of RBP-4 as controller for insulin resistant in type 2 diabetic in further studies must take into consideration other renal problems.

Association of retinol binding protein4 (RBP4) and ghrelin plasma levels with insulin resistance and disease severity in non-diabetic patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with insulin resistance (IR). Retinol binding protein 4 (RBP4) and ghrelin are two bioactive proteins that have been involved in glucose metabolism and IR, but also in the regulation of immune and inflammatory processes. The aim of this study was to determine the serum levels of RBP4 and ghrelin in patients with HS, and to assess the possible relationship between these levels and IR, disease severity and HS risk. A total of 137 subjects (77 HS patients and 60 controls) without diabetes mellitus were enrolled in this cross-sectional study. Patients with HS had significantly higher RBP4 but lower ghrelin plasma levels than controls, independently of body mass index (BMI). Serum RBP4 levels were positively correlated to disease severity and IR in HS patients. However, we found no association between ghrelin levels and any clinical or laboratory parameters. Moreover, high serum RBP4 and low ghrelin levels were associated with an increased risk for HS. Our results suggest that high RBP4 levels may be a surrogate biomarker for IR in patients with HS. Moreover, increased RBP4 and decreased ghrelin levels could also be independent risk factors for the development of HS.

Association of retinol binding protein-4, cystatin C, homocysteine and high-sensitivity C-reactive protein levels in patients with newly diagnosed type 2 diabetes mellitus.

IntroductionTo investigate the serum retinol binding protein (RBP)-4, cystatin C (Cys C), homocysteine (HCY) and high-sensitivity C-reactive protein (hs-CRP) levels in newly diagnosed type 2 diabetes mellitus (NT2DM) patients, prediabetes mellitus (PDM) subjects and normal controls, as well as their correlation with clinical and laboratory indexes, such as blood pressure and lipoprotein.Material and methodsA total of 242 subjects, including 141 NT2DM patients, 48 PDM subjects and 53 healthy controls, were recruited in the present study. Serum RBP-4, Cys C and hs-CRP concentrations were measured by enzyme-linked immunosorbent assay (ELISA). HCY concentration was determined by the chemical luminescence method.ResultsThere were significant differences in Cys C and hs-CRP among NT2DM patients, PDM subjects and normal controls. In comparison to controls, there were significantly elevated Cys C and hs-CRP levels in PDM (both p < 0.001), and a significantly increased Cys C level in NT2DM (p < 0.001); however, there were no significant differences in Cys C and hs-CRP levels between NT2DM and PDM, and no significant differences of hs-CRP levels between NT2DM and normal controls. No significant differences of RBP-4 and HCY levels among NT2DM, PDM and normal control groups were observed.ConclusionsAberrant Cys C expression and its clinical associations in NT2DM suggest their important role in this disease.

Serum retinol binding protein 4 is negatively related to estrogen in Chinese women with obesity: a cross-sectional study.

BackgroundThe association between serum Retinol Binding Protein 4 (RBP4) and obesity is still controversial. Serum RBP4 levels varies by gender, and estradiol may play a role in the difference. To investigate the participation of sex hormones in the association of RBP4 and obesity in humans, we measured serum RBP4, BMI, and sex hormones in 87 women from the outpatient.MethodsEighty-seven subjects of Chinese women origin from the outpatient (aged 40.22 ± 15.54 years) were enrolled. Subjects with diseases affecting the metabolic state or not suitable to participate in this study were excluded. Anthropometrics and laboratory tests, including lipid profile, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), estradiol (E2),progesterone (PROG), testosterone (TESTO), and dehydroepiandrosterone (DHEA) were conducted. Serum RBP4 was detected by an enzyme immunoassay kit and validated by quantitative Western blotting.ResultsCirculating RBP4 levels were positively associated with BMI, waist circumference, waist-to-hip ratio (WHR), systolic and diastolic (SBP), diastolic blood pressure (DBP), triglycerides (TG), low high-density lipoprotein cholesterol(LDL-c), and testosterone (TESTO) in the total group. While only in obese individuals, serum RBP4 levels were negatively associated with E2. The highest value was in the subjects with both obesity and the low estrogen level. Multiple linear regression analysis revealed that RBP4 correlated independently with TG, TC and insulin in all subjects, TC in non- obese individuals. However, E2 were significantly associated with serum RBP4 only in obese individuals.ConclusionsRBP4 could be a marker of obesity-related factors; estrogen was negatively related to RBP4 and might be one of the influential factors.

Retinol binding protein 4 in relation to diet, inflammation, immunity, and cardiovascular diseases.

Retinol binding protein 4 (RBP4), previously called retinol binding protein (RBP), is considered a specific carrier of retinol in the blood. It is also an adipokine that has been implicated in the pathophysiology of insulin resistance. RBP4 seems to be correlated with cardiometabolic markers in inflammatory chronic diseases, including obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases (CVDs). It has recently been suggested that inflammation produced by RBP4 induces insulin resistance and CVD. The clinical relevance of this hypothesis is discussed in this review. Knowledge concerning the association of RBP4 with inflammation markers, oxidative stress, and CVDs as well as concerning the role of diet and antioxidants in decreasing RBP4 concentrations are discussed. Special attention is given to methodologies used in previously published studies and covariates that should be controlled when planning new studies on this adipokine.

Retinol binding protein-4 predicts incident diabetes in Asian Indian men with prediabetes.

The association of retinol binding protein-4 (RBP4) with incident type 2 diabetes (T2DM) in Asian Indian middle-aged men with impaired glucose tolerance (IGT) was studied. This was an ancillary analysis of a subsample from a cohort of participants with IGT in a 2 year prospective diabetes prevention program in India. For this analysis, 71 incident T2DM and 76 non-diabetic cases (non-progressors) based on the final glycemic outcome were selected. Baseline serum RBP4 was measured using competitive enzyme immunoassay. Correlations of RBP4 with relevant anthropometric and biochemical variables and also its association with diabetes were assessed using appropriate statistical analyses. Participants who developed T2DM had higher levels of serum RBP4 (21.3 [IQR: 17.7-24.9] µg/mL) compared with non-progressors (17.3 [IQR: 13.1-21.0] µg/mL; P = 0.001). Levels of RBP4 were lower than in Caucasians. Stepwise linear regression analysis showed that body mass index (BMI), systolic blood pressure, triglycerides, and HbA1c had independent associations with RBP4 levels. Multiple logistic regression analyses showed that RBP4 was independently associated with incident diabetes (odds ratio [OR] [95%confidence interval (CI)]: 1.69 [1.18-2.41]; P = 0.004). Adjustment for study group, age, BMI, waist circumference, 2 H plasma glucose, triglycerides, gamma glutamyl transferase, and insulin resistance weakened the significance of its association (OR [95%CI]: 1.65 [1.03-2.66]; P = 0.038).The results of this preliminary analyses showed that baseline serum RBP4 levels were independently associated with incident diabetes in Asian Indian men with IGT. It may be used as an additional predictor of future diabetes.

Associations of retinol-binding protein 4 with oxidative stress, inflammatory markers, and metabolic syndrome in a middle-aged and elderly Chinese population

BackgroundRetinol-binding protein 4 (RBP4), a novel adipokine secreted by adipocytes and the liver, has elevated levels in type 2 diabetes mellitus (T2DM). However, its association with human metabolic diseases remains controversial. The present study was designed to investigate the associations of plasma RBP4 levels with oxidative stress, inflammatory markers, and metabolic syndrome (MetS) in a Chinese population.MethodWe evaluated plasma RBP4 levels in a cross-sectional sample of 1748 Chinese men and women aged 50 to 70 years in Guangzhou using an in-house developed and validated sandwich ELISA. Plasma glucose, insulin, lipid profile, serum adiponectin, adipocyte fatty acid-binding protein (A-FABP), 8-iso-prostaglandin F2α (8-iso PGF2α), 13-(S)-hydroxyoctadecadienoic acid (13-HODE), high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL6), monocyte chemotactic protein 1 (MCP1) and tumor necrosis factor α (TNFα) were all measured. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans.ResultsCirculating RBP4 levels were positively correlated with A-FABP (r = 0.104, P < 0.001), 8-iso PGF2α (0.236, P < 0.001), and 13-HODE (0.204, P < 0.001) and were inversely correlated with HDL cholesterol (r = −0.072, P = 0.004). After multivariable adjustment, the RBP4 levels were strongly associated with MetS and its components. The ORs (95% CIs) for the comparisons of the extreme quartiles of RBP4 were 3.46 (2.87, 4.42) for MetS, 5.92 (4.47, 8.02) for hypertriglyceridemia, 1.42 (1.11, 1.68) for reduced HDL cholesterol, 1.87 (1.48, 2.36) for central obesity and 2.74 (2.15, 3.36) for hyperglycemia (all P < 0.001). When we further controlled for adipokines, markers of oxidative stress and proinflammatory response, the association of RBP4 with central obesity was abolished but not the association with other MetS components.ConclusionsPlasma RBP4 levels are associated with an adverse profile of oxidative stress and inflammatory markers and an increased risk of MetS in this Chinese population. These associations are independent of conventional risk factors.

Serum retinol binding protein 4 and clinical outcome in postoperative biliary atresia

Biliary atresia (BA), a chronic inflammatory disease of bile ducts, is characterized by the obliteration of bile flow. The aim of the present study was to investigate serum retinol binding protein 4 (RBP4) in postoperative BA patients and the association of RBP4 with clinical parameters and liver stiffness scores. A number of forty-eight BA patients post Kasai operation and 24 controls were enrolled. None of the patients had undergone liver transplantation. BA patients were classified into two groups according to their serum total bilirubin (TB) levels (non-jaundice, TB<2mg/dl vs. jaundice, TB≥2mg/dl) and liver stiffness (insignificant fibrosis, liver stiffness <7kPa vs. significant fibrosis, liver stiffness ≥7kPa). Serum RBP4 levels were determined by enzyme-linked immunosorbent assay (ELISA). Liver stiffness scores were measured by FibroScan. BA patients had lower RBP4 levels (14.9±1.0 vs. 18.7±1.0ng/ml, P=0.02), but higher liver stiffness than controls (29.5±3.3 vs. 5.0±0.5kPa, P<0.001). Serum RBP4 levels were significantly decreased in BA patients with jaundice, compared with those without jaundice (9.5±0.9 vs. 18.2±1.2ng/ml, P<0.001). Moreover, BA patients with significant liver fibrosis displayed lower serum RBP4 than those with insignificant fibrosis (14.1±1.2 vs. 21.2±1.4ng/ml, P=0.02). Further analysis showed that serum RBP4 was strongly correlated with liver stiffness and serum albumin (r=-0.72, P<0.001, and r=0.65, P<0.001, respectively). BA patients with portal hypertension (PH) had lower serum RBP4 than those without PH (12.8±1.2 vs. 19.2±1.7ng/ml, P=0.003). Serum RBP4 levels decreased in BA patients compared with normal participants, and its levels declined significantly in patients with more severe disease. RBP4 may play a role in the pathogenesis of hepatic fibrosis and serve as a possible biomarker reflecting disease severity in postoperative BA patients.

Association of Serum Retinol Binding Protein 4 with Adiposity and Pubertal Development in Korean Children and Adolescents

Retinol binding protein 4 (RBP4) has been postulated to provide a new link between obesity and insulin resistance. We aimed to assess the relationship between serum RBP4 and insulin resistance by investigating serum RBP4 levels in children and adolescents according to degree of obesity and pubertal stage. A total of 103 (30 lean, 39 overweight, 34 obese) were evaluated for serum RBP4, adiponectin, insulin, glucose and lipid profiles. RBP4 levels of obese and overweight groups were higher than those of lean group. RBP4 level was higher in pubertal group than in prepubertal group. RBP4 was positively correlated with age, height, weight, body mass index (BMI), abdominal circumference, systolic blood pressure, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol and triglyceride, and inversely with adiponectin. In the multiple linear regression analysis, RBP4 was found to be independently associated with pubertal stage, BMI and triglyceride but not with HOMA-IR. In conclusion, serum RBP4 level is related with degree of adiposity and pubertal development. The association of RBP4 with insulin resistance is supposed to be secondary to the relation between RBP4 and adipose tissue in children and adolescents.

Association of Retinol-Binding Protein-4 (RBP4) with Lipid Parameters in Obese Women

Although the adipokine retinol-binding protein-4 (RBP4) has been implicated in the development of obesity-related insulin resistance, its role in human obesity is still unclear. Our objectives were to find out the effect on RBP4 systemic levels of a weight loss induced by gastric bypass surgery and to analyze RBP4 relationships with insulin resistance, parameters of body composition, lipid metabolism, and inflammation. Sixty-three obese women were analyzed before and 12 months after surgery of systemic concentrations of RBP4, fasting glucose, insulin, lipid profile molecules, and inflammation-related proteins (C-reactive protein, tumor necrosis factor-alpha receptors 1 and 2, interleukin-18, and adiponectin), and waist and hip circumference measurements, body mass index calculation, and insulin resistance index by homeostasis model assessment were also made. We found that RBP4 levels were lower after weight reduction by gastric bypass surgery (p < 0.0001). We found RBP4 associated with triglycerides before (beta = 0.37, p = 0.02) and after surgery (beta = 0.59, p < 0.0001) and negatively with weight loss after surgery (beta = -0.37, p = 0.003). When expressed as a percentage of change, the decrease of RBP4 was related to the reduction in the levels of triglycerides and with the increase in HDL-cholesterol (beta = 0.73, p = 0.02 and beta = 0.62, p = 0.04, respectively). Others parameters analyzed, including inflammatory markers, were not related to RBP4. This study shows that, in obese women and after a substantial weight loss due to bariatric surgery, RBP4 was related to weight status and lipid parameters rather than to insulin sensitivity or inflammatory markers.

Association of retinol-binding protein-4 with dietary selenium intake and other lifestyle features in young healthy women

Objective This study specifically assessed plasma retinol-binding protein-4 (RBP4), an inflammatory marker, in young healthy women, with emphasis on its potential relations to dietary intake and lifestyle features. Methods Seventy-four women with a mean age of 20.5 ± 2.5 y and body mass index of 21.3 ± 2.3 kg/m 2 were enrolled. Anthropometric, blood pressure, glucose, lipid profile, RBP4, and insulin concentrations were determined. Nutritional intakes were estimated by a validated semiquantitative food-frequency questionnaire. Physical activity and smoking status were evaluated with appropriate tools. Results Regarding anthropometric and biochemical variables, only triacylglycerol concentration had a positive and significant association with plasma RBP4 concentrations ( P < 0.001). Trans fatty acid intake, vitamin A intake, and smoking time showed positive and significant correlations with RBP4 concentrations ( P < 0.05). Furthermore, individuals with a higher selenium intake ( P = 0.027), non-smoking participants ( P = 0.032), and subjects who self-declared to practice some physical activity ( P = 0.030) presented significantly lower RBP4 concentrations. Interestingly, selenium intake was inversely and significantly associated with RBP4 concentration ( P = 0.018) when adjusted for smoking status, energy intake, and vitamin C, vitamin E, and zinc intakes. Plasma RBP4 concentrations were also associated with smoking status ( P = 0.035), adjusted for potential confounding factors. Conclusion This translational research revealed that dietary intake of a nutrient with an impact on oxidative stress such as selenium and lifestyle features such as smoking habit can modulate RBP4 concentrations. Our results suggest that plasma RBP4 values could be a valuable tool to screen potential nutrient and inflammation interactions.

Influence of Age on the Association of Retinol‐binding Protein 4 With Metabolic Syndrome

The relationships of retinol-binding protein 4 (RBP4) with insulin sensitivity and body fat distribution have been investigated in a few recent studies with conflicting results. This may have been due to differences in ages of the subjects in the different studies. The aim of this study was to investigate whether the association of RBP4 and insulin sensitivity and percent trunk fat are influenced by age. Cross-sectional analyses of 48 young subjects and 55 elderly subjects. Insulin sensitivity was determined by a hyperinsulinemic-euglycemic clamp. Body fat distribution was determined by a dual-energy X-ray absorptiometry (DXA). In the young subjects, RBP4 levels were associated with insulin sensitivity (r = -0.30, P = 0.04), percent trunk fat (r = 0.54, P < 0.001), triglycerides (r = 0.44, P = 0.003), low-density lipoprotein (r = 0.38, P = 0.01). In contrast, in the elderly subjects there was no correlation between RBP4 levels and insulin sensitivity (r = -0.18, P = 0.20), percent trunk fat (r = 0.00, P = 0.10), triglycerides (r = 0.25, P = 0.10), and low-density lipoprotein (r = -0.11, P = 0.47). The associations of RBP4 with insulin sensitivity, percent trunk fat, and lipid levels are influenced by age.

Serum Retinol-Binding Protein-4, Leptin, and Adiponectin Concentrations Are Related to Ectopic Fat Accumulation

Serum retinol-binding protein 4 (RBP-4), leptin, and adiponectin concentrations identify insulin resistance in varied conditions, but their relationships with insulin sensitivity and ectopic fat accumulation are unclear. Our objective was to establish how these adipokines are related with intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content. We assessed retrospectively serum fasting RBP-4 concentrations in 1) 53 nondiabetic individuals in which insulin sensitivity and IMCL content were assessed by means of the insulin clamp and of 1H magnetic resonance spectroscopy of the calf muscles, and 2) 140 nondiabetic individuals in which insulin sensitivity and the IHL content were assessed by means of the updated homeostasis model assessment and of 1H magnetic resonance spectroscopy. In both experiments, serum leptin and adiponectin concentrations were measured. Fasting serum RBP-4, adiponectin, and leptin were associated with peripheral insulin sensitivity, were abnormal in the first-degree relatives of type 2 diabetic parents, and correlated with the soleus IMCL content and with the IHL content. The association of RBP-4 and adiponectin with insulin sensitivity was age, sex, and body mass index independent, but stepwise regression analysis suggested that RBP-4, but not adiponectin and leptin, was independently associated with insulin sensitivity. Adiponectin was independently associated with the IHL content, RBP-4, and leptin with the soleus IMCL content. Serum RBP-4 was a robust marker of insulin resistance. Serum RBP-4, leptin, and adiponectin concentrations reflected ectopic fat accumulation in humans.