Undercarboxylated osteocalcin correlates with insulin secretion in Japanese individuals with diabetes

Shogo Funakoshi; Kumiko Yoshimura; Seiki Hirano; Satoko Ohmi; Eri Amano; Yoshiharu Fukuda; Yoshio Terada; Shimpei Fujimoto

doi:10.1186/s13098-020-00579-3

Undercarboxylated osteocalcin correlates with insulin secretion in Japanese individuals with diabetes

Diabetol Metab Syndr. 2020 Aug 17:12:72. doi: 10.1186/s13098-020-00579-3. eCollection 2020.

Authors

Shogo Funakoshi¹, Kumiko Yoshimura^{1

2}, Seiki Hirano¹, Satoko Ohmi¹, Eri Amano¹, Yoshiharu Fukuda², Yoshio Terada¹, Shimpei Fujimoto¹

Affiliations

¹ Department of Endocrinology, Metabolism, and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505 Japan.
² Fukuda Clinic, Kochi, Kochi 780-0023 Japan.

Abstract

Background: Undercarboxylated osteocalcin (ucOC) is a secreted protein produced by osteoblasts that regulates insulin secretion and insulin sensitivity in rodents. However, the significance of these effects on glucose metabolism in human remains unknown. Moreover, the pathophysiological roles of ucOC on varying degrees of glucose intolerance, including diabetes need to be elucidated. In the present study, correlations between ucOC and indices of insulin secretion and sensitivity were analyzed in normal glucose tolerance (NGT), impaired glucose metabolism (IGM), and diabetes mellitus (DM) groups.

Methods: Based on 75 g OGTT data in Japanese individuals without diabetic medication, or medications which may affect ucOC levels, individuals were classified as having normal glucose tolerance (NGT), impaired glucose metabolism (IGM), or diabetes (DM). In each group, 25 individuals were consecutively recruited [total 75 individuals, age: 65 ± 11 (mean ± SD); BMI: 24.9 ± 3.8 kg/m²]. QUICKI and Matsuda index (MI) were calculated as insulin sensitivity indices. Homeostasis model assessment (HOMA)-β and insulinogenic index (IGI) were calculated as insulin secretion indices. UcOC was measured using ECLIA. Normally-distributed log_e-transformed (ln-) values were used for ucOC, HOMA-β, IGI, and MI.

Results: The ucOC was not significantly different among the three groups. The results of multiple regression analysis showed that ln-ucOC did not significantly correlate with age, sex, BMI, waist circumference, fasting plasma glucose, plasma glucose 120 min after glucose loading, fasting plasma immunoreactive insulin, ln-HOMA-β, QUICKI, or ln-MI in any of the three groups. Interestingly, ln-ucOC correlated with ln-IGI (r = 0.422, P = 0.0354) and HbA1c (r = - 0.574, P = 0.0027) only in the DM group. There was no significant correlation between ln-IGI and age, sex, BMI, or HbA1c in the DM group. Further, the results of multiple regression analysis showed that ln-IGI could be independently predicted by BMI (β = 0.598, P = 0.0014) and ln-ucOC (β = 0.641, P = 0.0007) in the DM group (R² = 0.488, P = 0.0006).

Conclusion: In our study, ucOC positively correlated with insulin secretion independently of BMI in Japanese individuals with diabetes. These results suggest that ucOC plays more important roles in insulin secretion than in insulin sensitivity in individuals with diabetes.

Keywords: BMI; Insulin secretion; Undercarboxylated osteocalcin.