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

Abstract

In the presence of obesity, beta-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 alpha- and beta-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 beta-cells was 2.1 +/- 0.9%, and the total beta-cell mass was 1.3 +/- 0.3 g. The relative volume of beta-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, r(2) = 0.64; DM, r(2) = 0.55; all subjects, r(2) = 0.38; P < 0.05). Notably, in type 2 diabetic patients, the ratio of alpha-cell area to beta-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 alpha-cell expansion and a decreased beta-cell fraction were predominantly observed in larger islets (islet area, >6415 micro m(2); P < 0.05) in control 1 and diabetic patients. The relative volume of beta-cell was found to be correlated with BMI in diabetic patients and normal organ donors. Moreover, decreased beta-cell but increased alpha-cell proportion in the islets suggests for a selective beta-cell loss in the pathogenesis of Korean type 2 diabetes.

Metabolic consequences of a 50% partial pancreatectomy in humans

“…This finding has often been used as a rationale for removing the pancreatic head in patients with chronic pancreatitis. In contrast, recent studies have demonstrated that, unlike in rodents, the distribution of islets in humans is rather homogeneous throughout the pancreas, with minimal differences in the respective beta cell content between the pancreatic head and tail only [39]. The present data lend support to these studies by showing that the quantitative impairment in post-challenge insulin secretion is rather similar in patients undergoing proximal and distal pancreatectomy.…”

Direct evidence of attempted beta cell regeneration in an 89-year-old patient with recent-onset type 1 diabetes

“…Despite the marked increase in beta cell replication, the number of beta cells was decreased to ∼20-30% of normal in this case [10,11]. The mechanism subserving this was presumably the increased beta cell apoptosis, now confirmed in freshly fixed pancreas tissue.…”

“…Again, there was a large degree of heterogeneity between different pancreas blocks (range 0.014-1.12%). In contrast, the fractional alpha cell area was within normal limits (0.56±0.08%, range 0.30-0.78%) [11].…”

“…2 and 3). The average number of CD4- The fractional beta cell area in the tumour-free pancreas sections of the patients was 0.54±0.2% of the total pancreatic area, corresponding to a deficit of ∼70-80% in fractional beta cell area compared with lean non-diabetic individuals [10,11]. Again, there was a large degree of heterogeneity between different pancreas blocks (range 0.014-1.12%).…”

An immune origin of type 2 diabetes?

“…Limited data are available on islet histology in type 2 diabetes. Although a decrease in beta cell volume, an increased number of alpha cells and the deposition of islet amyloid have been reported, it is not known whether tissue macrophages, dendritic cells or endothelial cells exhibit a proinflammatory phenotype [128,129,139,[156][157][158]. In diabetic patients, the presence of extensive islet amyloidosis does not appear to be associated with the influx of macrophages [159].…”