Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Pancreatology 2005;5:229–233 DOI: 10.1159/000085276 Beta-Cell Function and Insulin Resistance Evaluated by HOMA in Pancreatic Cancer Subjects with Varying Degrees of Glucose Intolerance Suresh T. Chari a Mauricio Zapiach a Dhiraj Yadav a Robert A. Rizza b a Division of Gastroenterology and Hepatology and b Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, Minn., USA Introduction When formally tested, most pancreatic cancer patients have glucose intolerance [1–3]. Depending on criteria used, between half and two thirds of pancreatic cancer patients have diabetes [2, 4]. Pancreatic cancer-associ- ated diabetes can occur at a resectable stage [2], but often remains undiagnosed till late in the course of the disease [5]. It is likely that pancreatic cancer-associated diabetes is a unique form of diabetes that is caused by the cancer because diabetes occurs with a high frequency in pancre- atic cancer, occurs in close temporal association with the diagnosis of cancer [5], and improves after resection of the tumor [6]. Understanding the pathogenesis of pancre- atic cancer-associated diabetes may yield clues to the di- agnosis of resectable pancreatic cancer. Increased insulin resistance [2, 3, 6, 7] and altered  - cell function (BCF) [3, 8, 9] occur in pancreatic cancer. However, it is unclear which defect is primary in the pathogenesis of pancreatic cancer-associated diabetes. To address this question, we measured fasting glucose and insulin concentrations in pancreatic cancer patients whose glucose tolerance ranged from normal to frank di- abetes. To estimate insulin resistance (IR) and BCF we used the homeostasis model assessment (HOMA) which estimates these parameters based on mathematical mod- eling [10]. Introduced in 1985 by Mathews et al. [10] , HOMA model has been extensively used to study insulin resistance and BCF in type 2 diabetes. While in an indi- Key Words Homeostasis model assessment   -Cell function  Insulin resistance  Pancreatic cancer  Diabetes Abstract Background/Aims: To gain insights into pathogenesis of pancreatic cancer-associated diabetes. Methods: Using homeostasis model assessment (HOMA), we estimated  -cell function (BCF) and insulin resistance (IR) from fast- ing plasma glucose (FPG) and insulin in 67 normoglyce- mic controls and 62 age- and BMI-matched normoglyce- mic pancreatic cancer patients. In addition, we studied 73 pancreatic cancer subjects with glucose intolerance; 21 had impaired FPG and 51 had diabetes. Results: BCF was similar in controls and normoglycemic pancreatic cancer subjects (64 8 5 vs. 78 8 9, p = ns), while IR was higher in pancreatic cancer subjects with normal FPG (1.6 8 0.6 vs. 1.1 8 0.1, p = 0.002). Among pancreatic cancer subjects, those with impaired FPG had markedly decreased BCF compared to those with normal FPG (44 8 5 vs. 78 8 9, p ! 0.02) without significant difference in IR (1.9 8 0.2 vs. 1.6 8 0.6, p = ns). In cancer subjects, those with diabetes had markedly increased IR com- pared to those with impaired FPG (3.2 8 0.3 vs. 1.9 8 0.2, p ! 0.0001), while the BCF was similar (37 8 4 vs. 44 8 5). Conclusion: Diabetes associated with pancreatic cancer is likely due to a combination of marked decline in BCF and increased insulin resistance. Copyright © 2005 S. Karger AG, Basel and IAP Received: October 27, 2003 Accepted after revision: May 19, 2004 Published online: April 22, 2005 Suresh T. Chari, MD 200 First St SW Mayo Clinic Rochester MN 55905 (USA) Tel. +1 507 266 4347, Fax +1 507 284 5486, E-Mail chari.suresh@mayo.edu © 2005 S. Karger AG, Basel and IAP 1424–3903/05/0053–0229$22.00/0 Accessible online at: www.karger.com/pan