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Selective ß-Cell Loss and -Cell Expansion in Patients with Type 2 Diabetes Mellitus in Korea

Department of Endocrinology and Metabolism, Immunology, and Cell Biology Core Laboratory, Institutes of Medical Science (K.H.Y., J.H.C.), and College of Nursing (H.S.K.), The Catholic University of Korea, Seoul, Korea 137-701; Keimyung University Dongsan Medical Center (I.K.L.), Daegu, Korea 700-712; and Joslin Diabetes Center (S.B.-W.), Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Kun-Ho Yoon, M.D., Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Kangnam St. Mary’s Hospital, #505, Banpo-Dong, Seocho-Ku, Seoul, Korea 137-701. E-mail: yoonk{at}catholic.ac.kr.

In the presence of obesity, ß-cell mass needs to be increased to compensate for the accompanying demands and maintain euglycemia. However, in Korea, the majority of type 2 diabetic patients are nonobese. We determined the absolute masses, relative volumes, and ratio of - and ß-cell in the pancreas and islets in normal and diabetic Korean subjects to correlate these findings with the clinical characteristics. Whole pancreases procured from organ donors were divided into 24 parts (control 1, n = 9). Tissue was also obtained by surgical resection after 35 partial pancreatectomies: in 25 diabetic patients, 10 age- and body mass index (BMI)-matched patients of benign or malignant pancreatic tumor without diabetes mellitus (DM) (control 2). Morphometric quantifications were performed. In control 1, the relative volume of ß-cells was 2.1 ± 0.9%, and the total ß-cell mass was 1.3 ± 0.3 g. The relative volume of ß-cells was found to be variable (control 1, 2.1 ± 0.9%; control 2, 1.9 ± 0.7%; DM, 1.4 ± 1.0%; P < 0.05 DM vs. control 1 and 2) and showed good correlation with BMI (control 1, r² = 0.64; DM, r² = 0.55; all subjects, r² = 0.38; P < 0.05). Notably, in type 2 diabetic patients, the ratio of -cell area to ß-cell area in the islet was higher than in control 1 and 2 (0.81 ± 0.4 vs. 0.29 ± 0.2, 0.20 ± 0.1, P < 0.05). Additionally, significant -cell expansion and a decreased ß-cell fraction were predominantly observed in larger islets (islet area, >6415 µm²; P < 0.05) in control 1 and diabetic patients. The relative volume of ß-cell was found to be correlated with BMI in diabetic patients and normal organ donors. Moreover, decreased ß-cell but increased -cell proportion in the islets suggests for a selective ß-cell loss in the pathogenesis of Korean type 2 diabetes.

This work was supported by grants from the Korean Ministry of Science and Technology (Critical Technology 21 on "Life Phenomena and Function Research") (00-J-LF-01-B-63) and the Korea Science and Engineering Foundation (R01-2001-000-00114-0).

Abbreviations: A/B ratio, Ratio of the area of -cells and ß-cells; BMI, body mass index; DM, diabetes mellitus.

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