Background Osteocalcin, a protein secreted mainly by mature osteoblasts, has been shown to be involved in glucose metabolism through various pathways. However, few studies has explored the association between osteocalcin and Time in range (TIR). Continuous glucose monitoring (CGM) -derived metrics, such as TIR and other indexes have been gradually and widely used in clinical practice to assess glucose fluctuations. The main purpose of this study was to investigate the correlation between osteocalcin and indexes from CGM in patients with type 2 diabetes mellitus (T2DM). Method The total number of 376 patients with T2D were enrolled, all of them performed three consecutive days of monitoring. They were divided into four groups on account of the quartile of osteocalcin. Time in range, Time below range (TBR), Time above range(TAR) and measures of glycemic variability (GV) were assessed for analysing. After a 100 g standard steamed bread meal, blood glucose (Glu0h Glu0.5 h, Glu1h, Glu2h, GLu3h), C-peptide (Cp0h, Cp0.5 h, Cp1h, Cp2h, Cp3h), serum insulin (INS0h, INS0.5 h, INS1h, INS2h, INS3h) concentrations at different time points were obtained. HOMA-IS, HOMA-βwas calculated to evaluate insulin sensitivity and insulin secreting of the participants. Results Patients with higher osteocalcin level had higher TIR (P < 0.05). Spearman correlation analysis showed that osteocalcin was positively correlated with TBR (although the P value for TBR was greater than 0.05) (r = 0.227, P < 0.001 r = 0.068, P = 0.189) and negatively correlated with TAR (− 0.229, P < 0.001). Similarly, there was a negative correlation between osteocalcin and glycemic variability (GV) indicators, including SD, MBG, MODD, ADDR, and MAGE (P value of MAGE > 0.05). Multiple stepwise regression showed that osteocalcin was an independent contributor to TIR, TAR and HOMA-IS. Conclusion Circulating osteocalcin is positively correlated with TIR and negatively correlated with MODD, ADDR, and MAGE. Osteocalcin may have a beneficial impact on glucose homeostasis in T2DM patients.

Background Time in range (TIR), a novel proxy measure of glucose control, is found closely related to diabetic microangiopathy and some other chronic complications, but the correlation between TIR and lower limb angiopathy has not been studied yet. Our purpose is to explore the relationship between TIR and abnormal ankle-brachial index(ABI) in type 2 diabetes. Methods We retrospectively collected patients’ information from the database and performed cross-sectional analysis. A total of 405 type 2 diabetes patients were enrolled in this study. ABI was measured and patients were stratified into low, normal, and high groups according to ≤ 0.9, > 0.9 and < 1.3, ≥ 1.3 ABI values. All patients underwent continuous glucose monitoring(CGM), and TIR was defined as the percentage of time in which glucose was in the range of 3.9–10 mmol/L during a 24-h period. Correlations between TIR and abnormal ABI were analyzed using Spearman analysis. And logistic regression was used to explore whether TIR is an independent risk factor for abnormal ABI. Results The overall prevalence of abnormal ABI was 20.2% (low 4.9% and high 15.3%). TIR was lower in patients with abnormal ABI values (P = 0.009). The prevalence of abnormal ABI decreased with increasing quartiles of TIR (P = 0.026). Abnormal ABI was negatively correlated with TIR and positively correlated with hypertension, age, diabetes duration, UREA, Scr, ACR, TAR, MBG, and M values (P < 0.05). The logistic regression revealed a significant association between TIR and abnormal ABI, while HbA1C and blood glucose variability measures had no explicit correlation with abnormal ABI. Additionally, there was a significant difference in LDL between the low and high ABI groups (P = 0.009), and in Scr between normal and low groups (P = 0.007). And there were significant differences in TIR (P = 0.003), age (P = 0.023), UREA (P = 0.006), ACR (P = 0.004), TAR (P = 0.015), and MBG (P = 0.014) between normal and high ABI groups, and in diabetes duration between both normal and low (P = 0.023) and normal and high (P = 0.006) groups. Conclusions In type 2 diabetes patients, abnormal ABI is associated with lower TIR, and the correlation is stronger than that with HbA1C. Therefore, the role of TIR should be emphasized in the evaluation of lower limb vascular diseases.

Background:Osteocalcin is a sort of protein secreted by osteoblast exclusively，and new observations have verified that glucose balance can be modulated by it in some ways. TIR has attracted more and more attention as an emerging blood glucose evaluation index. In this study, the association between TIR and the level of circulating osteocalcin was investigated in type 2 diabetes.METHODS376 patients with type 2 diabetes were enrolled in our trail, all of them performed three consecutive days of monitoring. And they were divided into four groups on account of the quartile of osteocalcin. TIR, Time below range(TBR）, Time above range(TAR) and measures of glycemic variability (GV) were assessed for analysing. After a 100g standard steamed bread meal, blood glucose (Glu0h Glu0.5h, Glu1h, Glu2h, GLu3h), C-peptide (Cp0h, Cp0.5h, Cp1h, Cp2h, Cp3h), serum insulin (INS0h, INS0.5h, INS1h, INS2h, INS3h) concentrations at different time points were obtained. HOMA-IS, HOMA-β was calculated to evaluate insulin sensitivity and insulin secreting of the participants.RESULTSTIR increased significantly as the osteocalcin level increased between groups (p < 0.05). No significant differences were found in gender composition, age, weight, BMI, diabetes duration, K+, Ca+, Creatinine, blood pressure among groups (respectively, p>0.05). Osteocalcin had positive correlation with TIR (r=0.227, P<0.001), while a negative correlation was presented in osteocalcin and TAR (-0.229, P< 0.001). Likewise, osteocalcin was negatively correlated with INS0h, INS0.5h, fasting blood glucose and postprandial blood glucose at any time point after intaking of a standard meal.Meanwhile, osteocalcin had a negative correlation with the majority of GV indexes including standard deviation (SD), mean blood glouse (MBG), mean of daily differences (MODD), average daily danger range (ADDR). Multiple stepwise regression analysis demonstrated that osteocalcin was an independent contributor of TIR, TAR, and HOMA-IS.CONCLUSIONSCirculating osteocalcin has a positive correlation with TIR, and is an protective factor of TIR and insulin sensitivity in type 2 diabetic patients.