Plasma soluble leptin receptor levels are associated with pancreatic β‐cell dysfunction in patients with type 2 diabetes

AIMS/INTRODUCTION A soluble form of the leptin receptor (soluble Ob-R) in the circulation regulates leptin's bioactivity, and is inversely associated with body adiposity and circulating leptin levels. However, no study has examined the clinical impact of soluble Ob-R on glucose metabolism in diabetes. The present study aimed to investigate the association of plasma soluble Ob-R levels with insulin resistance and pancreatic β-cell function in patients with type 2 diabetes. MATERIALS AND METHODS A total of 289 Japanese patients with type 2 diabetes were included in the present study. Fasting plasma soluble Ob-R levels and plasma leptin levels were measured by enzyme-linked immunosorbent assay. Insulin resistance and pancreatic β-cell function were estimated by homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function and fasting C-peptide index. RESULTS The median plasma soluble Ob-R level and plasma leptin level were 3.4 ng/mL and 23.6 ng/mL, respectively. Plasma soluble Ob-R levels were negatively correlated with homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function and the C-peptide index, whereas plasma leptin levels were positively correlated with each index in univariate analyses. Multivariate analyses including plasma soluble Ob-R levels, plasma leptin levels and use of sulfonylureas, along with age, sex, body mass index and other covariates, showed that soluble Ob-R levels were independently and negatively associated with homeostasis model assessment of β-cell function and the C-peptide index, but not significantly associated with homeostasis model assessment of insulin resistance. CONCLUSIONS Plasma soluble Ob-R levels are independently associated with pancreatic β-cell function, but not with insulin resistance, in patients with type 2 diabetes. The present study implicates the role of soluble Ob-R in pancreatic β-cell dysfunction in type 2 diabetes.