Ethnic differences and β-cell changes.

Ethnic differences in diabetes prevalence have led to investigations in the pathophysiologic mechanism that underlie the development of hyperglycemia among various races (1, 2). The pathogenesis of type 2 diabetes mellitus (T2DM) is closely associated with obesity and concomitant insulin resistance, sedentary lifestyle, and decreased insulin secretion (3). Asians have increased risk and rates of T2DM but, unlike Caucasians, are leaner yet more insulin-resistant. Studies of insulin secretion and resistance among South Asians (Indians) and East Asians (Chinese, Koreans, Filipino, and Japanese), who typically have lower mean body mass index (BMI) and waist circumference as compared with Caucasians of similar BMI and waist circumference, demonstrated reduced insulin secretion and increased insulin resistance (3). Studies in Asians identified the characteristic of increased visceral adiposity that has since become recognized as the abnormality that belies insulin resistance despite leaner BMI (4). For example, Filipino women in California with a normal Asian-adjusted BMI ( 23 kg/m) had a greater volume of intra-abdominal fat compared with white or African American women also with a normal BMI ( 25 kg/m) (5). Therefore, the available evidence argues that Asian ethnicity may predispose to greater deposition of fat in the visceral depot. Induced with modest weight gain, abnormal adipose tissue changes the expression of a number of adipocytokines and impedes the response of target organs liver, muscle, and kidney to insulin (3). A small BMI change but with adipose tissue distributed viscerally increases compensatory insulin secretion similar to changes seen in other ethnic groups with greater weight gain. The capacity of -cells to respond to insulin resistance appears to be different among Asians compared with Caucasians and suggests that the development of hyperglycemia and manifest diabetes are also ethnically different in the pancreas (6). Investigations of -cell mass or islet changes of the pancreas in humans are very difficult, and the clinical assessment of insulin secretions associated with cellular changes of the -cell is even more challenging. Studies that evaluate a stimulated response of and -cells provide invaluable assessment of overall capacity and/or dysfunction but do not offer insight to cellular changes that may account for the abnormal response. The preservation of pancreas tissue at autopsy offer an opportunity to examine morphohistologic changes and quantitate cellular mass and regenerative processes in disease and nondisease states among various ethnic groups. For this purpose, several reports have shown that -cell mass increases in obese individuals and decreases in diabetic individuals as compared with lean nondiabetic subjects. A reduction of approximately 50% of -cell mass has been reported by a number of investigators (7–10). These findings appear congruent with the conceptual understanding of the compensatory increase in -cell function observed with physiological demand such as pregnancy or abnormal demand in obesity and insulin resistance that precede reduced -cell mass and secretion in the development of T2DM and hyperglycemia (11). These findings suggest that cellular changes in the pancreas follow a pathway of similar processes from lean to obese to diabetic states in various ethnic groups. The study by Kou et al (12) in this issue presents results of a case-control study of nondiabetic, lean and obese Japanese individuals, characterizing differences in and -cells in pancreatic tissue. Eligible cases were identified postmortem (age 20–69 years with no history of diabetes or pancreatic disease or glucocorticoid use and autopsy performed within 24 hours), and pancreatic tissues were cytohistochemically examined and quantified for comparative analysis using standard statistical methods. Pancre-