Increased Circulating Osteoprotegerin Levels in Type 1 Diabetes Mellitus: A Systematic Review and Meta-analysis Based on Observational Studies

Objectives: Type 1 diabetes mellitus (T1D) has been disclosed to be associated with an elevated risk of cardiovascular disease (CVD), as well as increased risks of losing bone mass and progression of osteoporosis (OP). Osteoprotegerin (OPG), as a decoy receptor, has been demonstrated to play a critical role in bone metabolism homeostasis and vascular atherosclerotic diseases. This meta-analysis aimed to investigate the associations between OPG levels and T1D. Methods: Related literatures were searched and identified from the database of the Cochrane Library database, PubMed and EMbase inception to August 3, 2019 in English. The pooled standard mean difference (SMD) with its 95% confidence interval (CI) was calculated in using random-effect model analysis. Chi-square Q statistic and I-2 test were performed to evaluate and quantified the presence of heterogeneity. Results: Twelve studies with 1288 subjects (794 T1D patients and 494 healthy controls) were finally included. The incorporated results indicated that T1D patients have higher plasma/serum OPG levels than in healthy individuals (SMD = 0.64, 95% CI: 0.06, 1.22). Subgroup analyses suggested that Caucasian and glycosylated hemoglobin A1c (HbA1c) <8.5% groups showed higher OPG levels, however, there was no significant differences of OPG levels regarding subgroups of BMI >= or <25, children-adolescents or adults and HbA1c >= 8.5%. Conclusions: The current evidence suggested that circulating OPG levels are significantly higher in T1D than in healthy controls, and the increase of OPG levels are influenced by factors of race and HbA1c.