Associations of birthweight and history of childhood obesity with beta cell mass in Japanese adults

Abstract

Aims/hypothesis Low birthweight is associated with a high risk of diabetes, but there are no reports discussing birthweight and pancreatic tissues in humans. The purpose of this study was to examine the correlation between birthweight and beta and alpha cell mass in humans. Methods Sixty-four Japanese adults with and without diabetes who underwent pancreatectomy and were able to recall their weight history including birthweight were included. Pancreatic tissues were stained for insulin and glucagon, and fractional beta cell area (BCA) and alpha cell area (ACA) were quantified. Islet size and density and beta cell replication were also quantified and their associations with birthweight were evaluated. Results In participants without diabetes, there was a weak positive correlation between birthweight and BCA (R = 0.34, p = 0.03). The group with a history of childhood obesity, but not the group with a history of obesity in adulthood only, showed higher BCA compared with those without a history of obesity (1.78 ± 0.74% vs 0.99 ± 0.53%, p = 0.01), and the correlation coefficient between birthweight and BCA increased after excluding those with a history of childhood obesity (R = 0.51, p < 0.01). In those with diabetes, there was no correlation between birthweight and BCA. No correlation was found between birthweight and ACA in either those with or without diabetes. Conclusions/interpretation Birthweight and beta, but not alpha, cell mass are positively correlated in non-diabetic adults, and a history of childhood obesity may affect beta cell mass.

Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes

“…The characteristics of the participants have been reported previously [ 10 ] and are shown in ESM Table 1 . The Ethics Committee of Keio University School of Medicine approved this study.…”

“…Preoperative HbA 1c was measured by HPLC (HLC723G11; Tosoh, Tokyo, Japan). Participants were asked about their detailed weight trajectory using a questionnaire, as previously reported [ 10 ].…”

“…Surgically removed pancreatic specimens were quickly fixed in formaldehyde and embedded in paraffin for subsequent analysis. Then, 5 μm sections were cut from the tumour-free area and stained for light microscopy as follows: (1) with haematoxylin–eosin; (2) for insulin (peroxidase staining) with haematoxylin; (3) for glucagon with haematoxylin; and (4) for insulin and Ki67 for assessment of beta cell replication, as previously described [ 10 – 13 ].…”

“…However, because the studies did not compare these findings with those in diabetic individuals, it remains unclear how beta cell size and number are altered by diabetes. Therefore, using our previously published data [ 10 ], we here aimed to estimate the relative contribution of beta cell size and number to the reduction of BCM in individuals with type 2 diabetes.…”

Beta-Cell Mass in Obesity and Type 2 Diabetes, and Its Relation to Pancreas Fat: A Mini-Review

“…Since beta-cell replication is more frequently observed in the first five years of life [ 29 , 30 ], childhood obesity or birthweight might affect beta-cell mass. Indeed, we recently reported that the beta-cell area and birthweight were positively correlated in adults with NDM, and the beta-cell area in the group with a history of childhood obesity was increased compared with that in subjects without a history of obesity [ 26 ].…”