Altered Circulating Levels of Retinol Binding Protein 4 and Transthyretin in Relation to Insulin Resistance, Obesity, and Glucose Intolerance in Asian Indians

Pandey, Gautam Kumar; Balasubramanyam, Jayashree; Balakumar, Mahalingam; Deepa, Mohan; Anjana, Ranjit Mohan; Abhijit, Shiny; Anand, K.J.S.; Velmurugan, Kaliyaperumal; Miranda, Patrícia; Balasubramanyam, M; Mohan, Viswanathan; Gokulakrishnan, Kuppan

doi:10.4158/ep14558.or

Cited by 27 publications

(26 citation statements)

References 30 publications

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“…There is evidence to suggest that RBP4 and TTR play a role in the development of insulin resistance [ 1 , 12 , 29 ] and metabolic syndrome [ 30 – 32 ]. RBP4 was found to interrupt the insulin signaling cascade causing insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

“…TTR levels were reported to be elevated in T2DM subjects and to correlate positively with TG level [ 30 ]. Pandey et al have shown higher circulatory levels of RBP4 and TTR in T2DM subjects, as well as a significant association between T2DM and RBP4 (OR = 1.11, 95% CI: 1.01–1.21) and TTR (OR = 1.34, 95% CI: 1.17–1.55) after adjusting for confounding factors [ 12 ]. In the present study, subjects with FBG ≥100 mg/dl had significantly lower serum levels of RBP4 and higher levels of TTR than those with FBG < 100 mg/dl.…”

Section: Discussionmentioning

confidence: 99%

“…Transthyretin (TTR), a transport protein, carries RBP4 and the thyroid hormone, thyroxin (T4), through the blood [ 11 ]. Recently, a human study found that circulatory RBP4 and TTR is associated with glucose intolerance and obesity, and T2DM and RBP4 is associated with insulin resistance [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Association of retinol binding protein 4 and transthyretin with triglyceride levels and insulin resistance in rural thais with high type 2 diabetes risk

et al. 2018

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BackgroundRetinol binding protein 4 (RBP4), a protein secreted by adipocytes and bound in plasma to transthyretin (TTR), has been associated with obesity, the early phase of insulin resistance, metabolic syndrome, and type 2 diabetes mellitus. The objective of this study was to elucidate the relationship between RBP4, TTR, triglyceride (TG) and type 2 diabetes risk in rural Thailand.MethodsWe measured the serum RBP4, TTR, glucose, triglyceride and insulin levels, and glucose tolerance of 167 volunteers from Sung Noen District, Nakhon Ratchasima Province, Thailand. Student’s t-test, Pearson’s correlation and logistic regression analysis were used to evaluate the relationships between RBP4, TTR and type 2 diabetes markers.ResultsRBP4 and TTR levels, as well as homeostatic model assessment of insulin resistance (HOMA-IR) values, were significantly elevated among subjects with high triglyceride levels (p < 0.01, p < 0.05, p < 0.05, respectively). Triglyceride levels correlated with RBP4 (r = 0.34, p < 0.001) and TTR (r = 0.26, p < 0.01) levels, as well as HOMA-IR values (r = 0.16, p < 0.05). After adjustment for age and gender, the risk of hypertriglyceridemia was 3.7 times greater (95% CI =1.42–9.73, p = 0.008) in the highest RBP4 tertile as compared to the lowest tertile. Similarly, the highest TTR and HOMA-IR tertiles had greater risk of hypertriglyceridemia at 3.5 (95% CI = 1.30–9.20, p = 0.01) and 3.6 (95% CI = 1.33–9.58, p = 0.01) times higher than the respective lowest tertiles. The correlation between TTR and blood glucose was statistically significant (r = 0.18, p < 0.05), but not found this relationship in RBP4.ConclusionsThe associations of RBP4 and TTR with hypertriglyceridemia and insulin resistance may have important implications for the risk of heart disease and stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Association of retinol binding protein 4 and transthyretin with triglyceride levels and insulin resistance in rural thais with high type 2 diabetes risk

et al. 2018

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“…Results from a two-year prospective study of middle-aged Asian Indian men with impaired glucose tolerance where 71 incident type 2 diabetes and 76 non-diabetic cases were studied, found that baseline RBP4 levels were independently associated with incident diabetes (Ram et al 2015). Studies involving measures of both circulating RBP4 and TTR levels in age-matched individuals with normal glucose tolerance (n = 90), impaired glucose tolerance (n = 70) and type 2 diabetes (n = 90) identified that circulating levels of both RBP4 and TTR showed significant associations with glucose intolerance, obesity, and type 2 diabetes (Pandey et al 2015). Additionally, RBP4 but not TTR levels were found to be positively associated with insulin resistance (Pandey et al, 2015).…”

Section: Rbp4 Adipose Tissue and Adipose-related Metabolic Disordmentioning

confidence: 99%

Vitamin A signaling and homeostasis in obesity, diabetes, and metabolic disorders

Blaner

2019

Pharmacology & Therapeutics

202

174

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Much evidence has accumulated in the literature over the last fifteen years that indicates vitamin A has a role in metabolic disease prevention and causation. This literature proposes that vitamin A can affect obesity development and the development of obesity-related diseases including insulin resistance, type 2 diabetes, hepatic steatosis and steatohepatitis, and cardiovascular disease. Retinoic acid, the transcriptionally active form of vitamin A, accounts for many of the reported associations. However, a number of proteins involved in vitamin A metabolism, including retinolbinding protein 4 (RBP4) and aldehyde dehydrogenase 1A1 (ALDH1A1, alternatively known as retinaldehyde dehydrogenase 1 or RALDH1), have also been identified as being associated with metabolic disease. Some of the reported effects of these vitamin A-related proteins are proposed to be independent of their roles in assuring normal retinoic acid homeostasis. This review will consider both human observational data as well as published data from molecular studies undertaken in rodent models and in cells in culture. The primary focus of the review will be on the effects that vitamin A per se and proteins involved in vitamin A metabolism have on adipocytes, adipose tissue biology, and adipose-related disease, as well as on early stage liver disease, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

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“…It was reported that the level of circulating RBP4 is often elevated in obese mice and humans and that, under these circumstances, the protein induces insulin resistance [ 7 ]. Previous studies had suggested that circulating RBP4 levels were associated with insulin resistance [ 8 ], metabolic syndrome [ 9 ], impaired glucose tolerance [ 10 ], and type 2 diabetes [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes

et al. 2018

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The retinol-binding protein 4 (RBP4) has been postulated to play a role in glucose homeostasis, insulin resistance, and diabetes mellitus in human and animal studies. The aim of the present study was to evaluate the role of RBP4 in Chinese patients with type 2 diabetes mellitus with and without diabetic retinopathy (DR). Plasma RBP4 concentrations were tested in 287 patients with type 2 diabetes. At baseline, demographic and clinical information including presence of DR and vision-threatening DR (VTDR) was collected. The relationship between RBP4 and DR (VTDR) was investigated using logistic regression. Patients with DR or VTDR had significantly higher plasma levels of RBP4 on admission (P<0.0001). Receiver operating characteristics (ROCs) to predict DR and VDTR demonstrated areas under the curve for RBP4 of 0.79 (95% confidence interval (CI): 0.73–0.85) and 0.90 (95% CI: 0.85–0.94), respectively, which were superior to other factors. For each 1 μg/ml increase in plasma level of RBP4, the unadjusted and adjusted risk of DR would be increased by 8% (with the odds ratio (OR) of 1.08 (95% CI: 1.05–1.13), P<0.001) and 5% (1.05 (1.02–1.11), P=0.001), respectively. It was 12% (with the OR of 1.12 (95% CI: 1.07–1.18), P<0.001) and 9% (1.09 (1.05–1.15), P<0.001) for VTDR. The present study shows that elevated plasma levels of RBP4 were associated with DR and VDTR in Chinese patients with type 2 diabetes, suggesting a possible role of RBP4 in the pathogenesis of DR complications. Lowering RBP4 could be a new strategy for treating type 2 diabetes with DR.

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Altered Circulating Levels of Retinol Binding Protein 4 and Transthyretin in Relation to Insulin Resistance, Obesity, and Glucose Intolerance in Asian Indians

Cited by 27 publications

References 30 publications

Association of retinol binding protein 4 and transthyretin with triglyceride levels and insulin resistance in rural thais with high type 2 diabetes risk

Association of retinol binding protein 4 and transthyretin with triglyceride levels and insulin resistance in rural thais with high type 2 diabetes risk

Vitamin A signaling and homeostasis in obesity, diabetes, and metabolic disorders

Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes

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