ENDOCRINE PRACTICE Vol 21 No. 8 August 2015 861 Original Article Gautam Kumar Pandey, M.Tech; Jayashree Balasubramanyam, MS; Mahalingam Balakumar, MPharm; Mohan Deepa, PhD; Ranjit Mohan Anjana, MD, PhD; Shiny Abhijit, PhD; Anand Kaviya, MSc; Kaliyaperumal Velmurugan, MSc; Priya Miranda, PhD; Muthusamy Balasubramanyam, PhD; Viswanathan Mohan, MD, PhD; Kuppan Gokulakrishnan, MSc, PhD Submitted for publication November 26, 2014 Accepted for publication February 26, 2015 Madras Diabetes Research Foundation & Dr. Mohan’s Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai, 600086, India. Address correspondence to Dr. K. Gokulakrishnan, MSc, PhD, Scientist; Department Of Research Biochemistry, Madras Diabetes Research Foundation; 4, Conran Smith Road, Gopalapuram, Chennai - 600 086, India. E-mail: gokulmdrf@gmail.com, gokul@mdrf.in Published as a Rapid Electronic Article in Press at http://www.endocrine practice.org on June 29, 2015. DOI: 10.4158/EP14558.OR To purchase reprints of this article, please visit: www.aace.com/reprints. Copyright © 2015 AACE. ABSTRACT Objective: Retinol binding protein 4 (RBP4) has been implicated in metabolic disorders including type 2 diabe- tes mellitus (T2DM), but few studies have looked at trans- thyretin (TTR) with which RBP4 is normally bound to in the circulation. We report on the systemic levels of RBP4 and TTR and their associations with insulin resistance, obesity, prediabetes, and T2DM in Asian Indians. Methods: Age-matched individuals with normal glu- cose tolerance (NGT, n = 90), impaired glucose tolerance (IGT, n = 70) and T2DM (n = 90) were recruited from the Chennai Urban Rural Epidemiology Study (CURES). Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). RBP4 and TTR levels were measured by enzyme-linked immu- nosorbent assay (ELISA). Results: Circulatory RBP4 and TTR levels (in mg/ mL) were highest in T2DM (RBP4: 13 ± 3.9, TTR: 832 ± 310) followed by IGT (RBP4: 10.5 ± 3.2; TTR: 720 ± 214) compared to NGT (RBP4: 8.7 ± 2.5; TTR: 551 ± 185; P<.001). Compared to nonobese NGT individuals, obese NGT, nonobese T2DM, and obese T2DM had higher RBP4 (8.1 vs. 10.6, 12.1, and 13.2 mg/mL, P<.01) and TTR levels (478 vs. 737, 777, and 900 mg/mL, P<.01). RBP4 but not TTR was signifcantly (P<.001) correlated with insulin resistance even among NGT subjects. In regression analy- sis, RBP4 and TTR showed signifcant associations with T2DM after adjusting for confounders (RBP4 odds ratio [OR]: 1.107, 95% confdence interval [CI]: 1.008-1.216; TTR OR: 1.342, 95% CI: 1.165-1.547). Conclusion: Circulatory levels of RBP4 and TTR showed a signifcant associations with glucose intolerance, obesity, T2DM and RBP4 additionally, with insulin resis- tance. (Endocr Pract. 2015;21:861-869) Abbreviations: BMI = body mass index; CI = confdence interval; HDL = high-density lipoprotein; IGT = impaired glu- cose tolerance; LDL = low-density lipoprotein; NGT = normal glucose tolerance; OGTT = oral glucose tol- erance test; OR = odds ratio; RBP4 = retinol binding protein 4; T2DM = type 2 diabetes mellitus; TTR = transthyretin; WC = waist circumference INTRODUCTION The current pandemic of type 2 diabetes mellitus (T2DM) is closely associated with obesity and insulin resistance (1). Obesity is a rapidly growing lifestyle dis- order characterized by increased adipose tissue mass (2). Adipose tissue is a major source of many proteins (adipo- cytokines) that may directly contribute to vascular injury, diabetes, and atherogenesis (3,4). Recent studies have dem- onstrated the possible importance of the adipokine retinol binding protein 4 (RBP4) that is normally bound to trans- thyretin (TTR) in the circulation (5). Although the physi- ological function appears to be to bind retinol and prevent its loss through the kidneys (6), multiple mechanisms have been described by which RBP4 could affect changes in glucose and lipid metabolism (7). A potential link between the RBP4 and T2DM was suggested by Yang et al (8), who showed that RBP4 was elevated in insulin-resistant