Relationship of uncarboxylated osteocalcin concentrations and ucOC/cOC index with the glycemic status in type 2 diabetes mellitus

Abstract

BACKGROUND AND OBJECTIVE: It has been shown in cell cultures and animals that uncarboxylated osteocalcin (ucOC), produced by osteoblasts, increases β-cell proliferation as well as insulin and adiponectin secretion, which improve glucose tolerance and insulin sensitivity and prevents the development of diabetes. Thus, our objective is to analyze the association of the ucOC concentrations and the index ucOC/cOC with the glycemic status in patients with type 2 diabetes mellitus (T2DM) and control subjects (CS). RESEARCH DESIGN AND METHODS: In this study, serum concentrations of ucOC and carboxylated osteocalcin (cOC) were measured in 30 type 2 diabetic patients (age, 51.5±9.3) and 60 CS (age 45.5± 6.0). Mean BMI was not different between groups. The CS were nondiabetic and were screened to rule out metabolic syndrome. Additionally, all subjects were evaluated for fasting plasma glucose (FPG), insulin, HOMA and HbA1c. Statistical analysis was made using parametric, nonparametric tests, Fisher's exact test or X2, and Spearman test whenever appropriate. RESULTS: The median ucOC concentration of patients with T2DM and CS was 0.189 and 0.278 nmol/l, respectively (p<0.01, even when adjusted for age and creatinine). We classify the ucOC concentrations by quartiles. Based in our data in CS, 73.3% of type 2 diabetic patients had ucOC concentrations below percentile 50th, while 100% had ucOC concentrations below percentile 75th. FPG concentrations were 8.21, 7.08, 5.97 and 5.38 mmol/l in the ucOC quartiles one, two, three and four, respectively (quartile 1 vs quartile 4, p<0.01). HOMA index in subjects with ucOC concentrations within the lower and upper quartile groups was 5.16±3.96 and 2.43±1.62, respectively (p<0.05). Relationship of ucOC with FPG and HOMA in patients with T2DM was ρ=-0.362 and ρ= -0.253 (p<0.05), respectively. The median of the index ucOC/cOC in type 2 diabetic patients and non-diabetic control subjects was 0.11 and 0.53, respectively (p<0.001). Relationship of the index ucOC/cOC with FPG and HOMA was -0.423 (p<0.001) and -0.256 (p<0.05). Relationship of cOC with HbA1C was -0.544 (p<0.001) in patients with T2DM. CONCLUSIONS: Patients with T2DM have lower ucOC concentrations and lower index ucOC/cOC than CS. Additionally, ucOC and the index ucOC/cOC are negatively correlated with FPG and HOMA. While, cOC is inversely correlated with HbA1c.