Effects of Obesity and Diabetes on Beta-Cell Mass in Japanese

Abstract

The prevalence of type 2 diabetes mellitus (T2DM) continues to increase all over the world. T2DM is characterized by insulin resistance and β-cell dysfunction. Recent studies have shown that β-cell dysfunction, but not insulin resistance, is critical for the development of T2DM.1 Since Butler et al2 and other groups have reported reduced β-cell mass (BCM) in both lean and obese individuals with T2DM, it is now widely recognized that β-cell deficit is a core feature of T2DM. In adult humans, we and others have shown that BCM is increased by ap-proximately 20-50% in obese non-diabetic individuals in the Caucasian population.3,4 Increased workload of beta-cells may result in beta-cell death through various mechanisms such as hy-perglycemia, dyslipidemia (glucolipotoxicity), oxidative stress, endoplasmic reticulum (ER) stress, inflammatory cytokines, and amyloid deposition. Recent rodent studies have suggested that dedifferentiation of β-cells to α-cells is another cause of the reduction of BCM in T2DM.5However, the change in α-cell mass (ACM) in patients with diabetes is controversial. ACM has been reported to increase or decrease in patients with T2DM,6,7 while we and another Japanese study observed no significant increase in BCM in obese non-diabetic adults in the Japanese population.6,8 The mean body mass index (BMI) of Japanese patients with T2DM is <25 kg/m2, suggesting that about half of patients with T2DM are not even overweight (i.e.,BMI≥25 kg/m2, the definition of obesity in Asian countries). In contrast, most Caucasian patients with T2DM are obese, and the mean BMI of patients with T2DM is about 30 kg/m2. Considering the similar incidence of T2DM despite the lower degree of obesity in Japanese compared with Caucasians,9 these findings suggest that β-cell regenerative capacity may differ between Japa-nese and Caucasians. Because of the limited capacity of β-cell regeneration in Japanese, excess β-cell workload could be induced in individuals with less obesity compared with Caucasians.