Serum Retinol-binding Protein 4 Levels Research Articles

The association between retinol binding protein 4 and peripheral neuropathy in type 2 diabetic patient

Background & Objective: The most common microvascular consequence of diabetes is peripheral neuropathy. A very common ailment that has a significant impact on a patient's quality of life is peripheral neuropathy (PN). The purpose of this study was to look into the possible link between retinol binding protein 4 (RBP4) and peripheral neuropathy in individuals with type 2 diabetes mellitus (T2D), as the relationship between RBP4 and PN is still unclear. Methodology: We enrolled 152 participants who were matched for age and sex in a case control study during August and December 2023. There were 50 healthy controls, 50 diabetic patients without PN, and 52 diabetic patients with PN. ELISA was used to measure serum RBP4. Results: Diabetic individuals with PN had significantly greater serum levels of RBP4 than diabetic patients without PN (P ˂ 0.001). Increased age (r = 0.262, P ˂ 0.01), DM duration (r = 0.565, P ˂ 0.01), and BMI (r = 0.183, P ˂ 0.05) were all substantially linked with RBP4 levels. RBP4 levels exhibited a negative correlation with high-density lipoproteins (HDL) and a positive correlation with total cholesterol, triglycerides, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL). Conclusion: Elevated RBP4 level is strongly and independently linked with PN in type 2 diabetic patients, and may play an important role in PN progression. Abbreviations: DM - Diabetes mellitus; PN - peripheral neuropathy; PBP4 - retinol binding protein 4; T2D - type 2 diabetes mellitus Keywords: diabetes mellitus; peripheral neuropathy; retinol binding protein 4. Citation: Nafakhi IA, Abdalsada NH. The association between retinol binding protein 4 and peripheral neuropathy in type 2 diabetic patient. Anaesth. pain intensive care 2024;28(5):908−913; DOI: 10.35975/apic.v28i5.2563 Received: May 03, 2024; Reviewed: June 04, 2024; Accepted: August 23, 2024

Long-Term Prognostic Value of Adipocytokines in Patients with Acute Coronary Syndrome: An 8-Year Clinical Prospective Cohort Study.

To elucidate the predictive values of adipocytokines in patients with acute coronary syndrome (ACS). Overall, 297 patients with ACS were consecutively enrolled in this prospective cohort study between June 2015 and July 2017 and completed follow-up with a median follow-up time of 6.5 years. For consistency, the last visit date was June 20, 2023. Serum levels of retinol-binding protein-4 (RBP4), interleukin-1β (IL-1β), monocyte chemoattractant protein 1(MCP-1), adrenomedullin (ADM), netrin 1 (NTN 1), and omentin were measured using enzyme-linked immunosorbent assay. Follow-up data were collected during clinical visits or through telephone interviews at 1, 3, 6, 12 months, and annually. The primary endpoint was defined as major adverse cardiovascular events (MACEs), including all-cause mortality, rehospitalization for percutaneous coronary intervention, and severe angina requiring rehospitalization. All biomarkers displayed a good diagnostic ability of MACEs. The Kaplan-Meier curve showed that the cumulative survival rates of high level of RBP4, IL-1β, and MCP-1 and low level of the ADM, NTN1, and omentin had lower cumulative survival rates (Log rank tests: all p<0.05). After adjustment in the Cox hazard proportional model, the results were RBP4 ≥ 6.87 ng/mL, hazard ratio (HR)=2.512, p=0.003; IL-1β≥ 58.95 pg/mL, HR=3.809, p<0.001; MCP-1 ≥ 401.75 pg/mL, HR=4.047, p<0.001; ADM≤120.01 ng/mL, HR=3.930, p=0.008; NTN1 ≤63.7 pg/mL, HR=3.345, p=0.007; omentin ≤ 4.54 ng/mL, HR=2.830, p=0.004. P-values for interaction were > 0.05 in the sex, age, and dyslipidemia subgroups. Pro-inflammation adipocytokines RBP4, IL-1β, and MCP-1 increased and anti-inflammation biomarkers ADM, NTN1, and omentin decreased were independently associated with a higher risk of MACEs in patients with ACS.

Serum retinol binding protein 4 in individuals with essential hypertension and type 2 diabetes: A cross-sectional study.

Cardiometabolic disorders, notably primary hypertension and type 2 diabetes, present substantial global health challenges. The intricate interplay between metabolic and cardiovascular pathways has prompted extensive research into molecular mechanisms linking these conditions. The adipokine Retinol Binding Protein 4 (RBP4), initially recognized for retinol transport, has emerged as a potential biomarker in the network of metabolic and cardiovascular dysfunction. Recent studies implicate RBP4 in insulin resistance and its complications, including hypertension. This study explores RBP4 dynamics in patients with primary hypertension and type 2 diabetes, aiming to contribute valuable insights into diagnostic and therapeutic advancements in managing these interconnected disorders. This cross-sectional study, conducted over 2 years in a tertiary healthcare centre of North India, aimed to investigate the serum concentration of Retinol Binding Protein 4 (RBP4) in 119 participants diagnosed with primary hypertension and type 2 diabetes. Ethical guidelines were strictly followed, and comprehensive clinical assessments, including blood pressure measurements, were performed. RBP4 levels were quantified using an ELISA kit, alongside markers of insulin resistance. Statistical analyses, involving t-tests and correlation assessments, sought to unravel potential associations between RBP4, insulin resistance, and blood pressure parameters using SPSS 20.0. The study comprised 61 healthy control (HC) participants and 58 individuals diagnosed with both essential hypertension and type 2 diabetes (EH+T2D). EH+T2D participants were on average older (45.71 ± 9.29 years vs. 40.34 ± 9.47 years, P = 0.002). Dyslipidemia prevalence was markedly higher in EH+T2D (72.4% vs. 11.4%, P < 0.0001), accompanied by disrupted lipid profiles. Serum RBP4 concentration was significantly elevated in EH+T2D (49.17 ± 19.37 mg/L, P < 0.0001), suggesting its potential role in the shared pathophysiology of primary hypertension and type 2 diabetes. Pearson's correlation analysis revealed associations between RBP4 levels, metabolic, and cardiovascular parameters, underscoring its potential as a link between these conditions. Elevated serum RBP4 levels suggest its potential as a novel biomarker in the shared pathophysiology of primary hypertension and type 2 diabetes. The correlation analysis highlights the intricate interplay between metabolic, lipid, and cardiovascular parameters, emphasizing the need for holistic interventions.

Reappraisal of serum retinol-binding protein as a surrogate marker for retinol and discovery of a novel retinol estimation formula

Background & AimsSerum retinol (ROH) is commonly used for population level assessment of vitamin A status. High-performance liquid chromatography (HPLC) is considered most accurate method for measuring ROH. However, with the technical difficulty of using HPLC for routine assays, serum retinol-binding protein (RBP) measured by immunological assays is expected to be a surrogate marker for ROH, with reports of a close correlation between serum RBP and ROH. Nevertheless, RBP is not commonly tested to assess vitamin A status with concerns over RBP alterations under various physiopathological conditions. Thus, we reappraised the extent to which RBP could be used as a surrogate marker in representative disorders that alter serum RBP levels. As a related marker, diagnostic utility of transthyretin (TTR) was also evaluated. MethodsTo evaluate the reliability of ROH and RBP assays, specimen stability was assessed in terms of (1) storage at 25, 4, −20, and −80 ºC for 1−28 days, (2) five-cycle freeze-thawing, and (3) fluorescent light exposure for 1−14 days. Sources of variation (sex, age, body mass index [BMI], and drinking habits) and reference intervals for ROH, RBP, and TTR were determined in 617 well-defined healthy individuals. To investigate the influence of disorders that affect serum RBP, patients with five diagnostic groups were enrolled: 26 with chronic kidney disease (CKD); 13 with various malignancies in advanced stages (AdM), 12 with acute bacterial infections (ABI), 6 with liver cirrhosis (LC), and 26 with simple obesity (BMI ≥ 27 kg/m2). ResultsThe stability of RBP and ROH in serum was confirmed under all conditions. In healthy individuals, serum ROH, RBP, and TTR were appreciably high in males with a slight increase in proportion to age and BMI. The major-axis regression line between RBP (x) and ROH (y) in healthy individuals was y = x, with a correlation coefficient of 0.986. In the LC, AdM, and ABI groups, similar strong correlations were observed; however, the regression lines were shifted slightly rightward from the healthy group line, indicating a positive bias in estimating ROH. Interestingly, the same analyses between TTR and ROH revealed similar strong linear relationships in all groups; however, the regression line of each group showed a leftward (opposite) shift from the healthy group line. Based on these observations, we developed a novel regression model composed of RBP and TTR, which proved to be accurate in estimating ROH, even under these pathological conditions. ConclusionsThe perfect RBP-ROH correlation in healthy individuals indicates the utility of RPB as a surrogate marker for ROH. Nevertheless, under RBP-altered conditions, a slight overestimation of ROH is inevitable. However, when the TTR was tested together, the bias can be corrected almost perfectly using the novel ROH estimation formula comprising RBP and TTR.

Clinical value of retinol binding protein, C-reactive protein and urine microalbumin in patients with chronic renal disease and ischemic cerebrovascular disease.

To explore the diagnostic value of retinol binding protein (RBP), C-reactive protein (CRP) and urine microalbumin (UMA) for ischemic cerebrovascular disease (ICD) in patients with chronic kidney disease (CKD). In this study, a total of 118 patients with CKD were selected and grouped into two groups: a group of patients who were complicated with ICD (CKD+ICD group, n=58), and a group of patients with CKD only (CKD group, n=60). Then, the patients in the CKD+ICD group were further classified into a good prognosis group and a bad prognosis group according their modified Rankin scale score at sixth months after discharge. Serum RBP, CRP and urine UMA levels were compared between the CKD group and CKD+ICD group. The diagnostic efficiency of serum RBP, CRP and urine UMA levels for ICD in patients with CKD was analyzed. The receiver operating characteristic (ROC) curve was used to assess their prognostic performance. Logistic regression analysis was used to evaluate the risk factors for poor prognosis of patients with CKD and ICD. The levels of RBP, CRP, and UMA in the CKD+ICD group were significantly higher than those in the CKD group (all P<0.05). RBP demonstrated the highest diagnostic accuracy and sensitivity for ICD in CKD patients, while CRP and UMA exhibited equivalent specificity, surpassing that of RBP. ROC curves showed that the areas under the curve (AUCs) of RBP and CRP were significantly greater than that of UMA (P<0.05) and there was no significant difference for AUCs between RBP and CRP. In addition, the levels of RBP, CRP and UMA in the poor prognosis group were significantly higher than those in the good prognosis group (all P<0.05). Logistic regression analysis showed that RBP, CRP and UMA were independent risk factors for the poor prognosis of patients with CKD and ICD (Odds ratios =2.507, 3.677 and 1.919, respectively; all P<0.05). The assessment of RBP, CRP and UMA is recommended for diagnosis of ICD in CKD patients. RBP, CRP and UMA are independent risk factors for poor prognosis of CKD patients with ICD.

Does Retinol-Binding Protein 4 (holo- and apo-RBP4) Increase or Remain Constant in Sera from Patients with Hypothyroidism?

Retinol-binding protein 4 (RBP4) is a retinol transporter in the blood plasma. Many diseases alter the plasma or serum levels of RBP4. Since serum RBP4 concentrations have been reported to decrease in hyperthyroidism, this study investigated whether serum RBP4 concentrations increased or remained constant in hypothyroidism. In sera from patients with hypothyroidism (n=71), hyperthyroidism (n=30), and healthy subjects (n=20), serum concentrations of RBP4 (sum of holo- and apo-RBP4), retinol, albumin, creatinine, and related constituents were measured, and RBP4/retinol molar ratio (as an index of apo-RBP4) and estimated glomerular filtration rate (eGFR) were calculated. The results showed that serum RBP4 concentrations tended to increase with decreasing free thyroxine concentrations, but there were no significant differences among patients with hypothyroidism, hyperthyroidism, and healthy subjects. When patients with hypothyroidism were subdivided by serum RBP4 level using 2.1 μmol/L cut-off value, patients with >2.1 μmol/L were revealed to be patients with older age having lower tri-iodothyronine, higher holo-RBP4, higher apo-RBP4, higher retinol, higher RBP4/retinol molar ratio, and lower eGFR than those in patients with <2.1 μmol/L. Multiple regression analysis showed significant associations between serum RBP4 levels and explanatory variables (retinol and eGFR). Although serum levels of RBP4 prior to the onset of renal dysfunction may affect the present concentrations, we conclude that the increase of serum RBP4 (both holo- and apo-RBP4) in patients with hypothyroidism was attributed to the decline in eGFR. In contrast, serum RBP4 concentration remained constant without renal dysfunction.

Retinol-Binding Protein 4 and Visfatin Levels in Patients with Periodontitis and Obesity/Overweight: A Systematic Review and Meta-Analysis.

Prior studies demonstrated an equivocal conclusion about the association between the level of retinol-binding protein 4 (RBP4)/visfatin and periodontitis patients with obesity. The aim of our study (Prospero ID: CRD42023469058) was to systematically review the available articles linking the biofluid levels of RBP4/visfatin to the comorbidity of periodontitis and obesity. Clinical trials were screened in accordance with specific inclusion criteria from seven databases up to November 2023. A quality assessment was performed with the Newcastle-Ottawa Scale and ROBINS-I tools for observational and interventional trials, respectively. The standard mean difference (SMD) with a 95% confidence interval (CI) related to the RBP4 level was recorded; the other indicators related to the visfatin level were measured via the mean difference (MD) with the corresponding 95% CI, and Fisher's Z transformation was measured to reveal the association using Review Manager 5.4. The current evidence was based on five observational studies and two interventional studies. All of them were included in the systematic review, and six of them were in the meta-analysis. Statistical analysis indicated that there was no significant difference in the circulating levels of RBP4 in the periodontitis patients with obesity or without, who were labeled as OP or NP, respectively (155 OP-107 NP: SMD = 1.38; 95% CI: -0.18-2.94, p = 0.08), as well as the periodontal healthy patients with a normal weight, who were labelled as NnP (116 OP-79 NnP: SMD = 6.76; 95% CI: -5.34-18.87, p = 0.27). Meanwhile, a significant higher level of serum visfatin was found in the OP patients than that of the NP (86 OP-45 NP: MD = 4.21; 95% CI: 2.65-5.77, p < 0.00001)/NnP (164 OP-88 NnP: MD = 13.02; 95% CI: 7.34-18.70, p < 0.00001) group. In addition, a positive association was observed between the serum RBP4 and body mass index/clinical attachment loss (CAL). And, then, there was a positive association between the serum visfatin and periodontal parameters, including the probing depth, CAL, and plaque index, as well as metabolic parameters, including the total cholesterol, triglycerides, fasting blood glucose, and low-density lipoprotein cholesterol. Here, the circulating RBP4 level was not independently related to the comorbidity of periodontitis and obesity, while serum visfatin was significantly associated with periodontitis and obesity. Notably, the positive association between circulating RBP4/visfatin and the periodontal parameters/metabolic parameters firmly suggested that the higher severity of the obese or periodontal status was associated with an elevated level of serum visfatin or RBP4 in the OP group. With more rigorous longitudinal research, the exact causations between RBP4/visfatin and the patients affected by obesity and periodontitis could be disentangled. RBP4 and visfatin might be novel, enlightening prospective bio-indexes for the targeted treatment of comorbidities.

The level of serum retinol-binding protein is associated with diabetic mild cognitive impairment

BackgroundSeveral studies have shown that retinol-binding protein (RBP) is linked to diabetes and neurodegenerative diseases. However, no studies have elucidated the relationship between RBP and diabetic cognitive disorders. ObjectiveTo determine whether the change characteristics of serum RBP are associated with alterations in cognitive functioning in type 2 diabetes mellitus (T2DM). MethodsIn this study, 252 patients with T2DM and 34 people as healthy controls were included. According to the Montreal Cognitive Assessment (MoCA), the diabetic subjects were divided into the mild cognitive impairment (MCI) group and the Non-MCI group. Demographic characteristics and clinical indicators as well as serum RBP levels were analyzed. ResultsThe serum RBP levels in the MCI group were lower compared with the Non-MCI group (P = 0.02). The level of RBP was higher in the diabetes without MCI group than in the healthy control (P < 0.001). Serum RBP levels were positively correlated with MoCA scores (r = 0.178, P = 0.003). Binary Logistic regression model analysis showed that low RBP [odds ratio (OR) = 0.936], old age (OR = 1.074), high fasting blood glucose (OR = 1.164), and low fasting C-peptide (OR = 0.722) may be independent risk factors for diabetic MCI. The ROC curve of serum RBP for predicting diabetic MCI showed that the area under the curve was 0.630. ConclusionsOur study revealed an association between serum RBP and diabetic MCI. Serum RBP levels in diabetic MCI are lower and correlated with cognitive function.

Effect of non-surgical periodontal treatment on cytokines/adipocytokines levels among periodontitis patients with or without obesity: a systematic review and meta-analysis

BackgroundThe objective of this systematic review and meta-analysis was to evaluate the effects of non-surgical periodontal therapy (NSPT) on inflammatory-related cytokines/adipocytokines in periodontitis patients with or without obesity.MethodsWe followed the preferred reporting items for systematic reviews and meta-analyses statement and registered the study (CRD42022375331) in the Prospective International Register of Systematic Reviews. We screened randomized-controlled trials and controlled clinical trials from six databases up to December 2022. Quality assessment was performed with RoB-2 and ROBINS-I tools for randomized trials and non-randomized trials, respectively. Meta-analysis was carried out using a random-effect model.ResultsWe included seventeen references in the systematic analysis, and sixteen in the meta-analysis. Baseline results of pro-inflammatory biomarkers, including serum interleukin (IL)-6, serum and gingival crevicular fluid (GCF), tumor necrosis factor (TNF)-a, serum C-reactive protein (CRP)/hs-CRP, and serum and GCF resistin, were higher in obesity subjects than in normal weight subjects. The effect of NSPT with respect to levels of cytokines/adipocytokines, including IL-6, TNF-a, CRP/hs-CRP, resistin, adiponectin, leptin and retinol binding protein 4 (RBP4), were then analyzed in the systematic and meta-analysis. After three months of NSPT, serum (MD = -0.54, CI = -0.62 – -0.46), and GCF (MD = -2.70, CI = -4.77 – -0.63) levels of IL-6, along with the serum RBP4 (MD = -0.39, CI = -0.68–0.10) decreased in periodontitis individuals with obesity. NSPT also improved GCF adiponectin levels after three months (MD = 2.37, CI = 0.29 – 4.45) in periodontitis individuals without obesity.ConclusionsObese status altered the baseline levels of cytokines/adipocytokines (serum IL-6, serum and GCF TNF-a, serum CRP/hs-CRP, and serum and GCF resistin). Then NSPT can shift the levels of specific pro-inflammatory mediators and anti-inflammatory mediators in biological fluids, both in obesity and non-obesity individuals. NSPT can reduce serum and GCF IL-6 levels together with serum RBP4 level in individuals with obesity after 3 months, besides, there is no sufficient evidence to prove that obese patients have a statistically significant decrease in the levels of other cytokines compared to patients with normal weight. NSPT can also increase GCF adiponectin level in normal weight individuals after 3 months. Our findings imply the potential ideal follow-up intervals and sensitive biomarkers for clinical bioanalysis in personalized decision-making of effect of NSPT due to patients’ BMI value.

ОЦЕНКА ЭФФЕКТИВНОСТИ ПРИМЕНЕНИЯ АНАЛОГА ЧЕЛОВЕЧЕСКОГО ГЛЮКАГОНОПОДОБНОГО ПЕПТИДА-1 ЛИРАГЛУТИДА У ПАЦИЕНТОВ С ПОДАГРОЙ И МЕТАБОЛИЧЕСКИ НЕЗДОРОВЫМ ФЕНОТИПОМ ОЖИРЕНИЯ

Introduction. Obesity is a global problem of the XXI century. The most important aspect of metabolic disorders that develop with obesity is a change in the level of serum uric acid (UA) in the blood and the development of gout. Currently, the dynamics of cardiovascular risk factors in patients with obesity on the background of drug therapy is being widely studied. The aim of our study is to study the level of UA, vaspin (VsP), visfatin (VF), omentin (ITLN1), retinol-binding protein-4 (RBP4) in patients with gout and metabolically unhealthy obesity (MNHO) during diet therapy and 3 months of treatment with the drug from the group of human glucagon-like peptide-1 analog (aGLP-1) Liraglutide. Materials and methods: 25 men with gout were examined, the average age was 43.6±7.3 years. Gout was diagnosed according to the classification criteria ACR/EULAR, 2015, Wallace S.L., 1977. Metabolic syndrome was established according to the criteria of GNCA (2013): abdominal obesity - waist circumference ≥ 94 cm in combination with any 2 from the following criteria - an increase in triglycerides (TG) ≥ 1.7 mmol / l; a decrease in high-density lipoproteins (HDL) &lt; 1.0 mmol / l, an increase in low-density lipoproteins (LDL) ≥3.0 mmol / l, blood pressure (BP) ≥ 140/90 mm Hg; increase in plasma glucose ≥ 6.1 mmol / l. At the time of inclusion in the study, all patients had an interictal period of gout. Body mass index (BMI) was calculated using the Quetelet formula: body weight (kg)/height (m²). To assess the type of distribution of adipose tissue, the waist circumference (WT, cm) and hip circumference (HB) were measured with a flexible centimeter tape, with the calculation of the W/H ratio. The concentration of VsP, VF, ITLN1, RBP4 was studied using the enzyme-linked immunosorbent assay method using the kits; the concentration of the level of UA in blood serum and daily urine was studied using the colorimetric method. Liraglutide was injected into the subcutaneous fat of the anterior abdominal wall at a dose of 0.6 mg once a day for the first week. Escalation by 0.6 mg every week was then recommended until a dose of 18 mg per day was reached. Participants then received injections at a dose of 1.8 mg for 3 months. Thus, the observation period was 3 months. Laboratory studies and assessment of anthropometric parameters were carried out initially, as well as after 3 months. The control group consisted of 16 healthy men matched in age. Statistical data processing was carried out using the statistical software package Statistica 13.0. Results. 3 months after treatment, a statistically significant decrease in body weight, BMI and WC was noted (in all cases, p&lt;0.01). Median BMI before treatment was ˗ 38.4 [35.4; 39.2] kg/m², against the background of ongoing therapy - 33.2 [31.4; 34.2] kg/m², and thus the loss of body weight was 23% (p&lt;0.05). Serum UA level decreased by 30.1% (p&lt;0.05) during therapy with a drug from the GLP-1 group. In patients with gout, BMI and regression of obesity were associated with a significant decrease in VsP by 17.2%, VF by 13.8% and RBP4 by 10.4%, and a significant increase in ITLN1 by 12.6%. A direct correlation was established between BMI and WC with the content of VsP, RBP4 and VF in blood serum (correlation coefficients from 0.44 to 0.57, p&lt;0.05) and an inverse correlation with the content of ITLN1 (correlation coefficient -0.29, p&lt;0.05). A direct correlation was found between the serum UA index and the content of VsP, VF, RBP4 (correlation coefficients from 0.31 to 0.49, p&lt;0.05). Conclusion. Patients with gout in combination with MNZO showed a significant increase in serum levels of UA, VsP, RBP4 and VF, against the background of a decrease in the concentration of ITLN1. The use of diet therapy using a drug from the GLP-1 group showed a statistically significant decrease in BMI, WC, serum UA, pro-inflammatory adipokines (VsP, VF and RBP4), and a significant increase in anti-inflammatory cytokines (ITLN1).

The Influence of Thyroid Hormones on Levels of Lipid Profile and Adipokine in Iraqi Women with Thyroid Disorders

Hypothyroidism and hyperthyroidism are prevalent endocrine diseases.These have significant implications for lipid synthesis, mobilization, and metabolism. Retinol-binding protein 4 is a new adipokine implicated in some physiological and pathological processes, such as metabolic and endocrine disorders. Its elevation aids in the diagnosis of thyroid problems. The present study includes 60 women with thyroid diseases; 30 of them have hypothyroidism and 30 have hyperthyroidism. This study includes 20 healthy women as a control group. For each participant anthropometric, biochemical Thyroid-stimulating hormone, triiodothyronine, Thyroxine, lipid profile, and retinol binding protein-4 are measured. The results show that hypothyroid women have significantly higher levels of total cholesterol, triglycerides, and lowdensity lipoprotein cholesterol as compared to the hyperthyroid or control group. The serum of total cholesterol, triglycerides, and low-density lipoprotein cholesterol are significantly lower in hyperthyroid women compared to the hypothyroid or control group. In addition, there are no significant differences in blood high-density lipoprotein cholesterol concentrations among the three groups. Furthermore, serum retinolbinding protein-4 levels were higher in the hyperthyroid group compared to the hypothyroid or control groups. According to the findings of this study, hypothyroidism causes dyslipidemia, which raises the risk of cardiovascular disease while hyperthyroidism causes abnormalities in lipid profiles. Additionally, hyperthyroidism causes an increase in serum retinol-binding protein-4 levels in the blood.

Predictive value of serum retinol binding protein in severity and complications of acute pancreatitis: a retrospective cohort study

Objectives Retinol binding protein (RBP) is associated with an increased risk of insulin resistance, metabolic syndrome, atherosclerosis and hypertension. This study aimed to evaluate serum RBP levels in patients with acute pancreatitis (AP). Methods The study included 1,871 AP patients, including 1,411 with mild AP (MAP), 244 with moderately severe AP (MSAP), and 186 with severe AP (SAP). Retrospective analysis was conducted on RBP concentrations and other clinical data of AP patients. Results AP patients were subgrouped by RBP level into low RBP (LRBP), normal RBP (NRBP), and high RBP (HRBP) groups. The LRBP group showed a significantly higher proportion of SAP patients than NRBP and HRBP groups. Additionally, the LRBP group had the highest BISAP and CTSI scores among the three groups; WBC and CRP levels in the NRBP group were significantly lower than those in the LRBP and HRBP groups. RBP was better at predicting acute necrotic collection (ANC) than other local complications, with an area under the curve (AUC) of 0.821. RBP was also an independent risk factor for acute lung injury (ALI) and ANC in AP patients. The AUC of RBP for predicting ALI was 0.829, with 30.45 mg/L as the optimal cutoff value, and the sensitivity and specificity were 59.70% and 96.50%, respectively. The AUC of RBP for predicting ANC was 0.821, with 28.35 mg/L as the optimal cutoff value, and the sensitivity and specificity were 61.20% and 95.50%, respectively. Conclusions Serum RBP had predictive value for AP severity, local and systemic complications.

Targeting Retinol-Binding Protein 4 (RBP4) in the Management of Cardiometabolic Diseases.

The ancient use of herbs for the treatment of various human diseases have been documented, with several scientific literatures supporting the use of medicinal plants. There is however a major concern about the phyto-constituents in the plants that performs the healing function and the mechanism by which it works for different ailments are still a research prospect. Cardiometabolic disease (CMD) is no doubt becoming more frequent globally and this is due to poor approach in therapy, contrary effects linked with intensive control, inept strategies with old drugs, inadequate control of some risk factors and lack of knowledge of the pathophysiological mechanisms that lead to this malaise. Retinol-binding protein 4 (RBP4) are predominantly secreted in the liver and adipose tissues and several researches have observed that elevation in serum levels of RBP4 often observed in obese experimental animals and human subjects causes CMD (obesity, insulin resistance, hyperlipidemia, etc.). RBP4 has gained special attention in the last 20years in the field of metabolism research. This review aims to show research interaction of some medicinal plants targeting RBP4 in treating CMD and to encourage researchers, who are interested in CMD drug design, to focus on medicinal plants that inhibit the secretion of serum RBP4 in the adipose tissue for therapeutic approach to CMD. It also aims to identify the major bioactive compounds of plants that serves as a better and cheaper drug candidate for CMD and also study the signaling pathway which the plant material uses to regulate the metabolic consequences.

Study pattern of nutritional recovery in edematous and non-edematous malnourished children after a short hospital stay of nutrition rehabilitation

Background: Severe acute malnutrition (SAM) is a state of deficiency that manifests itself in two forms: edematous and non-edematous. There have been significant advances in the clinical management of this disease state, but to date, data on nutritional recovery outcomes are scarce. Aims: We aimed to compare nutritional recovery in edematous and non-edematous malnourished children. Subjects and Methods: This is a prospective observational study of 98 children (3 – 60 months) with SAM (25 edematous and 73 non-edematous) receiving nutritional rehabilitation, according to the WHO guidelines, during a short hospitalization (SH) of 21 days. Results: Complete biochemical and nutritional recovery was completed in both edematous and non-edematous groups as indicated by normalized serum levels of retinol-binding protein, transthyretin, albumin, transferrin, fibronectin and hemoglobin, as well as C-reactive protein and acid alpha glycoprotein. Biochemical and nutritional recovery was faster in edematous children compared to non-edematous, as indicated by the significant difference (p &lt; 0.001) in the rate of recovery of albumin, transthyretin, and retinol-binding protein. At discharge, despite full biochemical nutritional recovery there remains a severe stunting in both groups with the persistence of moderate wasting in the non-edematous group. Conclusions: Complete biochemical and nutritional recovery can be achieved after short hospitalization for nutritional rehabilitation and an early discharge of children cured is possible for edematous children but not convincing in non-edematous ones, as they remained moderately malnourished. Key words: nutritional rehabilitation, short hospitalization, recovery, edematous, non-edematous.

Retinol-Binding Protein 4 Actives Adipocyte Renin–Angiotensin System via Toll-Like Receptor 4

Abstract Background To investigate the relationship between the levels of serum adipokine retinol-binding protein 4 (RBP4) levels and essential hypertension as well as to explore the role and mechanism of RBP4-induced activation of renin–angiotensin system (RAS) in hypertension in adipocyte. Methods From December 2016 to March 2019, 96 hypertensive patients without treatment and 64 healthy nonhypertensive subjects were recruited. The difference in serum RBP4 levels between the 2 groups was compared, and the relationship between serum RBP4 and hypertension was analyzed by multivariate logistic regression. In mouse primary white adipocytes, the effect and mechanism of RBP4 on RAS in adipocyte were determined by experiment of adenovirus transfected RBP4 overexpression. Protein expression of Toll-like receptor 4 (TLR4) and RAS key components was determined by western blotting. The level of angiotensin II (Ang II) in cell supernatant was measured by enzyme-linked immunosorbent assay. We also observed the effect of TLR4 inhibitor TAK242 on RAS activation induced by RBP4 overexpression. Results Serum RBP4 levels were significantly higher in patients with essential hypertension than in healthy nonhypertensive subjects [30.14 (23.76–40.65) vs. 25.05 (20.05–31.04) µg/ml, P &amp;lt; 0.01]. Multivariate logistic regression analysis showed that RBP4 was independently associated with hypertension [OR 1.10 (95% CI 1.06–1.14), P = 0.002]. In RBP4-transfected adipocytes, the expression of angiotensin-converting enzyme, angiotensinogen, renin/angiotensin-forming enzyme 1, and angiotensin II receptor 1, as well as the level of Ang II in cell supernatant (P &amp;lt; 0.05) were significantly increased. Whereas, activation of RAS system was markedly reduced when RBP4-transfected adipocyte was treated by TAK242 (P &amp;lt; 0.05). Conclusions Serum RBP4 is associated with hypertension. TLR4-mediated activation of RAS might be mechanisms underlying the effects of RBP4 on blood pressure.

Evaluation of maternal serum SERPINC1, E-selectin, P-selectin, RBP4 and PP13 levels in pregnancies complicated with preeclampsia

Objective The aim of this study is to investigate whether Serpin clade C (SERPINC1), E-selectin, P-selectin, Placental protein 13 (PP13), and Retinol-binding protein-4 (RBP4) levels in maternal serum were associated with the presence of preeclampsia and to compare them with uncomplicated pregnancies. Methods This prospective study included 40 women with preeclampsia and 40 healthy pregnant women. An enzyme-linked immunosorbent assay kit was used to measure serum SERPINC1, E-selectin, P-selectin, PP13, and RBP4 levels. Results The preeclampsia group had significantly higher E-selectin and P-selectin levels than the control group. PP13 and SERPINC1 levels were also significantly lower than the control group. There was no significant difference in RBP4 levels. The receiver operating characteristic curve revealed the best cutoff values for the following: E-selectin >19.2 ng/mL, with 87.5% sensitivity and 95% specificity; P-selectin >5.1 ng/mL, with 97.5% sensitivity and 100% specificity; PP13 ≤ 107.03 pg/mL, with 72.5% sensitivity and 77.5% specificity; and SERPINC1 ≤ 87.76 ng/mL, with 100% sensitivity and 97.5% specificity. Conclusion In this study, the endothelial dysfunction parameters SERPINC1, PP13, E-selectin, and P-selectin were found to be associated with preeclampsia. Endothelial dysfunction biomarkers in maternal non-serum body fluids may differ. More research is needed, especially to determine the relationship between SERPINC1 and preeclampsia.

Association of Leptin and Retinol Binding Protein 4 with the Risk of Gestational Diabetes: A Systematic Review and Meta-Analysis of Observational Studies.

The positive correlation between serum levels of retinol binding protein 4 (RBP4) and gestational diabetes (GDM) has been proven in the previous meta-analysis on case-control studies. However, its association with serum levels of leptin is not studied in any meta-analysis. Therefore, we performed an updated systematic review of observational studies evaluating the association between serum RBP4 and leptin with the risk of GDM. A systematic search was performed on four databases, including PubMed, Scopus, Web of Science, and Google Scholar, up to March 2021. After screening and deleting duplicates, nine articles met our inclusion criteria. Studies had case-control and cohort design, and included 5074 participants with a mean age range between 18 and 32.65 years (2359 participants for RBP4 and 2715 participants for leptin). Interestingly, this meta-analysis revealed higher levels of RBP4 (OR=2.04; 95% CI: 1.37, 3.04) and leptin (OR=2.32; 95% CI: 1.39, 3.87) are significantly associated with the increased risk of overall GDM. The subgroup analysis approved the results based on the study design, trimester of pregnancy and serum/plasms to investigate the source of heterogeneity. The present meta-analysis determines serum leptin and RBP4 levels as predictors of GDM occurrence. However, studies included in this meta-analysis showed significant heterogeneity.

Elevated retinal retinol-binding protein 4 levels in diabetic mice can induce retinal neurodegeneration through microglia.

Retinol-binding protein 4 (RBP4) is the sole specific transport protein for vitamin A (retinol), but it is also an adipokine with retinol-independent, proinflammatory activity associated with diabetes and diabetic retinopathy (DR). Most previous studies focused on the relationship between elevated serum RBP4 levels and DR. Since serum RBP4 cannot cross the blood-retinal barrier, the level of retinal RBP4 is independent of serum RBP4, and the change of retinal RBP4 and its potential pathogenic mechanism in DR has not been studied. We showed that the retinal RBP4 levels were raised in Streptozotocin-induced diabetic mice though the serum RBP4 levels were decreased. Intravitreal injection of RBP4 protein in mice results in activation of microglia, loss of retinal ganglion cells (RGCs) and bipolar cells. Minocycline (MC) can reverse the activation of microglia induced by RBP4, protecting RGCs and bipolar cells. These findings suggest that retinal RBP4 levels were raised in diabetic mice, and RBP4 can directly induce retinal neurodegeneration in mice through microglia. RESEARCH HIGHLIGHTS: We revealed that the retinal RBP4 levels were raised in diabetes and elevated retinal RBP4 can induce retinal neurodegeneration through microglia. Inhibition of neuroinflammation or reduction of retinal RBP4 level may be a potential therapeutic strategy to prevent diabetic retinal neurodegeration.

Correlation of serum RBP4 level with oxidative stress and unstable carotid plaque in patients with cerebral infarction.

ObjectivesThis study aimed to investigate the changes in serum levels of retinol-binding protein 4 (RBP4) with cerebral infarction, relationship of RBP4 with oxidative stress and carotid atherosclerosis, and its possible role in cerebral infarction.Materials and methodsAccording to the results of cervical vascular ultrasound, the experimental group was divided into three groups: intima thickening group (n = 31), stable plaque group (n = 51), and unstable plaque group (n = 54). Forty healthy subjects were selected as the control group. Their serum levels of RBP4, 8-iso-prostaglandin-F2alpha (8-iso-PGF2α), and catalase (CAT) were measured. Carotid vascular ultrasound was used to measure the plaque area and intima-media thickness (IMT).ResultsThe serum RBP4 and 8-iso-PGF2α levels, IMT and plaque area in the control, intimal thickening, stable plaque, and unstable plaque groups increased, while the serum level of CAT decreased (P < 0.001). The serum levels of RBP4 positively correlated with 8-iso-PGF2α, IMT, and plaque area and negatively correlated with CAT level. The area under the receiver operating characteristic curve was 0.778 in predicting unstable plaques.ConclusionsThe serum levels of RBP4 were significantly elevated in elderly patients with cerebral infarction and correlated with oxidative stress injury and the degree of atherosclerosis. Serum RBP4 has diagnostic value for unstable plaques in carotid arteries.

Serum Levels of CXCL-13, RBP-4, and IL-6, and Correlation Analysis of Patients with Graves' Disease.

Objective To investigate the serum levels of CXC chemokine 13 (CXCL-13), retinol binding protein-4 (RBP-4), and interleukin 6 (IL-6) in patients with Graves' disease (GD). The correlation between CXCL-13, RBP-4, and IL-6 levels and the basal metabolic rate (BMR) was analyzed. Methods 118 GD patients diagnosed in our hospital were selected as the observation group from March 2017 to December 2018. According to the measured BMR value, 118 GD patients were divided into the mild group (n = 39), the moderate group (n = 47), and the severe group (n = 32), three subgroups. 60 healthy subjects were selected as the control group. The serum levels of CXCL-13, RBP-4, IL-6, TSH, FT3, and FT4 in every group were measured. Pearson correlation analysis was used to observe the correlation of serum CXCL-13, RBP-4, and IL-6 levels with TSH, FT3, FT4, and BMR. Results The levels of serum CXCL-13, RBP-4, and IL-6 in the observation group were higher than those of the control group, and the differences were statistically significant (P < 0.05). The levels of serum CXCL-13, RBP-4, and IL-6 in the moderate and severe groups were higher than those in the mild group, and the differences were statistically significant (P < 0.05). The levels of serum CXCL-13, RBP-4, and IL-6 in the severe group were higher than those in the moderate group, and the differences were statistically significant (P < 0.05). Pearson correlation analysis showed that the serum levels of CXCL-13, RBP-4, and IL-6 in GD patients were negatively correlated with TSH levels and positively correlated with FT3 and FT4 levels. Serum CXCL-13, RBP-4, and IL-6 levels in GD patients were positively correlated with BMR (r = 0.915, r = 0.942, r = 0.926, P < 0.001). Conclusion Serum CXCL-13, RBP-4, and IL-6 levels are elevated in patients with GD, and with the aggravation of the disease, the serum CXCL-13, RBP-4, and IL-6 levels also increase, showing a positive correlation, which can be used as indicators to reflect the degree of GD.