Osteocalcin Is Related to Enhanced Insulin Secretion in Gestational Diabetes Mellitus

Abstract

OBJECTIVEThere is growing evidence that osteocalcin, an osteoblast-derived protein locally acting on bone formation, can increase insulin secretion as well as insulin sensitivity and thus prevent the development of obesity and diabetes in experimental animals. In humans, osteocalcin has been reported to be decreased in patients with type 2 diabetes. Because gestational diabetes mellitus (GDM) can serve as a model of pre–type 2 diabetes, the aim of this study was to investigate osteocalcin in GDM.RESEARCH DESIGN AND METHODSOsteocalcin measurement and an oral glucose tolerance test were performed in 78 pregnant women (26 women had GDM and 52 women had normal glucose tolerance [NGT] during pregnancy; women were matched for age and BMI) and in 34 women postpartum.RESULTSDuring pregnancy osteocalcin was significantly higher in the women with GDM than in the women with NGT (15.6 ± 6.4 vs. 12.6 ± 4.0 ng/ml; P < 0.015), whereas no difference was observed between the two groups at 12 weeks postpartum (36.2 ± 10.2 vs. 36.2 ± 13.0 ng/ml), when osteocalcin was found to be increased compared with the level in the pregnant state in all women (+145 ± 102% in GDM vs. +187 ± 119% in NGT; P < 0.0001). Moreover, osteocalcin showed a significant correlation with basal and total insulin secretion in the whole study group (R = 0.3, P < 0.01).CONCLUSIONSIn GDM osteocalcin was higher and thus less restrained than in women with NGT during pregnancy and furthermore correlated with insulin secretion parameters. Therefore, it could be hypothesized that osteocalcin can enhance insulin secretion in insulin-resistant states; alternatively an effect of hyperinsulinemia on osteocalcin secretion cannot be excluded.

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

“…Twelve weeks after giving birth, OC levels equaled between the two groups. These findings suggest a compensatory increase in OC in the presence of impaired glucose tolerance during pregnancy (53).…”

Osteocalcin, energy and glucose metabolism

“…Osteocalcin levels were elevated in GDM compared to non-diabetic pregnant women and they normalized in the postpartum period. It has been suggested that these findings would correspond to an adaptive mechanism to fight against the insulin resistance of GDM, but a direct effect of hyperinsulinemia on osteocalcin secretion could not be ruled out during this period (35).…”

The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism

“…Interestingly, plasma levels of osteocalcin are higher in women with gestational diabetes and positively correlate with the disposition index during pregnancy, but return to normal postpartum [35]. This observation suggests that raising serum osteocalcin levels could be part of the adaptive process initiated to counter glucose intolerance during gestational diabetes [35]. Levels of circulating osteocalcin have also been associated with a number of lipid abnormalities.…”

“…In contrast, serum osteocalcin has been positively correlated with the HOMA of beta cell function (HOMA-%B) in diabetic patients, before and after glycaemic control [33,34]. Interestingly, plasma levels of osteocalcin are higher in women with gestational diabetes and positively correlate with the disposition index during pregnancy, but return to normal postpartum [35]. This observation suggests that raising serum osteocalcin levels could be part of the adaptive process initiated to counter glucose intolerance during gestational diabetes [35].…”