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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 loge-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.

Abstract Background Recently, an integrated network analysis has revealed dysregulation in the metabolism of mannose, a glucose epimer, in severely obese individuals without diabetes. In addition, fasting plasma mannose levels (M0) are associated with insulin resistance independent of BMI. Since the association between mannose and insulin sensitivity (IS) in those with impaired glucose tolerance remains unknown, we aimed to investigate this association in individuals without severe obesity but with varying degrees of glucose tolerance. Methods Based on 75 g OGTT data in Japanese individuals without diabetic medication, 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 IS indices. M0 was assayed using HPLC. Normally-distributed loge-transformed (ln-) values were used for MI and leptin. Results In the simple regression analysis, ln-MI was negatively correlated with BMI (NGT: r = − 0.639, IGM: r = − 0.466, DM: r = − 0.613) and ln-leptin (NGT: r = − 0.480, IGT: r = − 0.447, DM: r = − 0.593) in all 3 groups. Ln-MI was not significantly correlated with M0 in NGT (r = 0.241, P = 0.245) and IGT (r = − 0.296, P = 0.152) groups, it was moderately and negatively correlated in the DM group (r = − 0.626, P

Abstract Background While the association of the prevalence of non-alcoholic fatty liver disease (NAFLD) with impaired glucose metabolism has been reported, the factors influencing glucose tolerance in NAFLD remain to be clarified. Methods Glucose tolerance of 131 Japanese patients diagnosed as NAFLD by histological findings of liver biopsy specimen was examined using 75 g-OGTT. According to Matteoni’s classification, patients were divided to 4 groups [M1 ~ 4, M1, 2: non-alcoholic fatty liver (NAFL); and M3, 4: non-alcoholic steatohepatitis (NASH)]. Based on the OGTT data, insulinogenic index (IGI) and QUICKI were calculated as indices of insulin secretion and insulin sensitivity, respectively. Plasma glucose 120 min after glucose loading (G120) was used as the index for glucose intolerance. Results Stepwise multiple regression analysis using G120 as a dependent variable and loge-IGI, QUICKI, sex, BMI, age, NAFL/NASH as independent variables revealed that loge-IGI (β = −0.595) and QUICKI (β = −0.323) are significant factors predicting glucose intolerance (R2 = 0.403), indicating an important role of insulin secretion in glucose tolerance. These findings accord with glucose intolerance as high as 89.7% in patients with impaired insulin secretion defined by ≤43.2 pmol/mmol (40 μU/mg) IGI. Stepwise multiple regression analysis using QUICKI as a dependent variable and NAFL/NAFLD, sex, BMI, and age as independent variables revealed that BMI (β = −0.469) and NAFL/NAFLD (β = −0.204) are significant factors predicting insulin sensitivity (R2 = 0.248). Conclusion Impairment of insulin secretion is the most important factor to predict glucose intolerance in NAFLD; severity of histological findings is associated with insulin sensitivity independent of adiposity in NAFLD.