Positive association of glucagon with bone turnover markers in type 2 diabetes: A cross-sectional study

The osteo-metabolic changes in type 2 diabetes (T2D) patients are intricate and have not been fully revealed. It is not clear whether glucagon is entirely harmful in the pathogenesis of diabetes or a possible endocrine counter-regulation mechanism to reverse some abnormal bone metabolism. This study aimed to investigate the association between glucagon and bone turnover markers (BTMs) in T2D patients.

A total of 3984 T2D participants were involved in a cross-sectional study in Shanghai, China. Serum glucagon was measured to elucidate its associations with intact N-terminal propeptide of type I collagen (P1NP), osteocalcin (OC), and β-C-terminal telopeptide (β-CTX). Glucagon was detected with a radioimmunoassay. Propeptide of type I collagen, OC, and β-CTX were detected using chemiluminescence. The diagnosis of T2D was based on American Diabetes Association criteria.

The concentration of glucagon was positively correlated with two BTMs [OC-β: 0.034, 95% CI: 0.004, 0.051, p = 0.024; CTX-β: 0.035, 95% CI: 0.004, 0.062, p = 0.024]. The result of P1NP was [P1NP-regression coefficient (β): 0.027, 95% CI: -0.003, 0.049, p = 0.083]. In the glucagon tertiles, P for trend of the BTMs is [P1NP: 0.031; OC: 0.038; CTX: 0.020], respectively.

Glucagon had a positive effect on bone metabolism. The concentrations of the three BTMs increased as glucagon concentrations rose. This implied that glucagon might speed up skeletal remodelling, accelerate osteogenesis, and promote the formation of mature bone tissue. At the same time, the osteoclastic process was also accelerated, providing raw materials for osteogenesis to preserve the dynamic balance. In view of the successful use of single-molecule as well as dual/triple agonists, it would be feasible to develop a preparation that would reduce osteoporosis in diabetic patients.