Study of Insulin Resistance in Patients With β Thalassemia Major and Validity of Triglyceride Glucose (TYG) Index Arif M. Ansari, MD,* Kamalakshi G. Bhat, MD,* Smitha S. Dsa, MD,* Soundarya Mahalingam, MD,* and Nitin Joseph, MD† Summary: Complications like impaired glucose tolerance and diabetes mellitus due to iron overload need early identification in thalassemia. We studied the proportion of insulin resistance in thalassemia major patients on chronic transfusion, identified insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride glucose (TYG) index, compared them and validated TYG index. In total, 73 thalassemia patients on regular transfusion for 3 years with serum ferritin > 1500 ng/mL were studied. Serum ferritin, fasting blood glucose, triglycerides, and insulin levels were measured, HOMA-IR, and TYG index calculated and analyzed. Mean fasting glucose, triglyceride, and serum insulin values were 104 mg/dL, 164.18 mg/dL, and 19.6 m IU/mL, respectively. Mean serum ferritin was 5156 ng/mL. Insulin resistance was prevalent in one third of thalassemia patients and showed increase with age and serum ferritin. Insulin resistance by HOMA-IR was 32% as against 16% by TYG index with a cut-off value of 4.3. Using receiver operating char- ecteristic curve analysis, it was found that, by lowering the value of TYG index to 4.0215, sensitivity improved to 78.3% (from 39.13%) with specificity of 70%. Hence, we recommend a newer lower cut-off value of 4.0215 for TYG index for better sensitivity and specificity in identifying insulin resistance. Key Words: β thalassemia, insulin resistance, HOMA-IR, TYG index (J Pediatr Hematol Oncol 2017;00:000–000) β thalassemia is an inherited disorder characterized by deficiency in the production of β globin chains resulting in ineffective erythropoiesis. 1 Iron overload of tissue due to inadequate or absence of chelation therapy can lead to damage in the liver, heart, and endocrine glands. 2 One of the important endocrine pathology due to iron overload in β thalassemia major is diabetes mellitus. 3 The prevalence of impaired glucose tolerance and diabetes in thalassemia major varies from 8.5% to 12.2% and 5.4% to 19.5%, respectively. 1 It can occur due to impairment of insulin secretion or due to insulin resistance. 4 However, insulin resistance ocurs before decreased insulin production and needs to be identified early. One of the methods to measure insulin resistance is homeostasis model assessment of insulin resistance (HOMA-IR) which is reliable and used in large epidemiological studies. 5,6 However, it requires the meas- urement of fasting serum insulin which is costly and not available in most of the laboratories of developing countries. 4 Insulin resistance can be measured by an alter- native method (triglyceride glucose [TYG] index) which is the product of fasting glucose and triglycerides and this is comparable with the HOMA-IR index. 6 METHODS A hospital-based cross-sectional study was conducted at a medical college hospital in coastal Karnataka, India from October 2015 to September 2016. β thalassemia patients aged 5 years and above who were on regular packed cell transfusions (10 to 15 mL/kg, every 3 to 4 wk) for at least 3 years with a serum ferritin value > 1500 ng/mL were included in the study. Subjects with β thalassemia inter- media, β thalassemia with history of diagnosed diabetes, hyperlipidemia, thyroid disorders, and receiving insulin or antidiabetic drugs were excluded from the study. Sample size was calculated based on the prevalence of diabetes in chronically transfused patients with β thalassemia major to be 13% as stated in a previous study and at 95% confidence interval and 80% power. After adjustment of the calculated sample size for finite population the final sample size was calculated as 73 patients. Patients were recruited into the study after getting the institutional ethics committee approval and informed con- sent/assent. A semistructured proforma was prepared to record the data. Patients were instructed not to consume any other medications (apart from chelators) before transfusion. All blood samples were obtained after an overnight 8 to 10 hours fasting. The fasting plasma glucose and trigly- cerides were analyzed immediately within 1 hour using COBAS 6000(E501) fully automatic clinical chemistry analyzer. Serum ferritin was assessed using COBAS 6000 (E601) using principle of enzyme chemiluminiscence immuno assay (ECLIA). The sample obtained for serum insulin was stored immediately at -20°C in the central laboratory. The serum insulin samples were analyzed in 2 batches, within 1 month after collection using human insulin enzyme-linked immunosorbent assay kit (DRG-Insulin ELISA KIT) as per the standard procedure by a trained biochemist. The insulin resistance was calculated using HOMA-IR index and TYG index from the obtained samples. The mathematical formula which was used for the calculation of HOMA-IR index and TYG index are as follows. 7 Received for publication March 2, 2017; accepted September 13, 2017. From the Departments of *Pediatrics; and †Community Medicine, Kasturba Medical College, Mangaluru, Manipal University, Karnataka, India. The authors declare no conflict of interest. Reprints: Kamalakshi G. Bhat, MD, Department of Pediatrics, Kasturba Medical College, Mangaluru, Manipal University, Karnataka 575001, India (e-mails: kamalakshibhat@gmail.com; kamalakshi. bhat@manipal.edu). Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. ORIGINAL ARTICLE J Pediatr Hematol Oncol  Volume 00, Number 00, ’’ 2017 www.jpho-online.com | 1 Copyright r 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.