关键词: 2型糖尿病, 骨钙素, 老年人, 甲状腺功能减退症, 超重

Abstract: Background　Osteocalcin，specifically synthesized and secreted by osteoblasts，is the most abundant non-collagen protein in the bone matrix.Osteocalcin plays a regulatory role in bone mineralization，but it has also been found to be closely involved in glycometabolism regulation by a growing number of studies.Objective　To explore the actions of osteocalcin in glucose metabolism and influencing factors in elderly patients with type 2 diabetes mellitus（T2DM）.Methods　In this study，a random sampling method was used to select 329 T2DM patients aged 60 and over who were hospitalized at the First Hospital of Lanzhou University from 2017 to 2018.Spearman rank correlation analysis was carried out to examine the associations of demographic factors（sex，age，BMI and course of T2DM） collected at admission with laboratory parameters such as serum homocysteine，uric acid，creatinine，25-hydroxyvitamin D，osteocalcin 〔less and greater than the median level of 11.73 μg/L were defined as low osteocalcin（n=165） and high osteocalcin（n=164），respectively〕，glycosylated hemoglobin（HbA1c），thyroid stimulating hormone（TSH），total thyroxine，plasma blood glucose（FPG），and 2-hour postprandial glucose（2 hPG）.The results of a 3-hour 100 g OGTT and a 3-hour insulin response test were obtained，including venous plasma glucose levels and insulin levels measured at 0，30，60，120 and 180 min during the tests.Basal insulin sensitivity and secretion were assessed with HOMA-IR，and HOMA-β，respectively.Post-challenge insulin secretion was assessed with AUCINS120/AUCGLU120 ratio，namely，the ratio of insulin AUC（0-120 min） to glucose AUC（0-120 min）.Results　Spearman rank correlation analysis showed that osteocalcin was negatively correlated with HbA1c，FPG，and 2 hPG，and positively correlated with TSH（P<0.05）.Compared with those with high osteocalcin，those with low osteocalcin showed lower average TSH level，but higher male ratio，higher average levels of FPG，2 hPG，HbA1c and HOMA-IR（P<0.05）.Osteocalcin did not vary significantly according to HOMA-β level and AUCINS120/AUCGLU120 ratio（P>0.05）.Among those with both T2DM and subclinical hypothyroidism（n=139），low osteocalcin was associated with higher HOMA-IR（P<0.05），but HbA1c，HOMA-β and AUCINS120/AUCGLU120 ratio showed no association with osteocalcin（P>0.05）.In those with normal thyroid function，low osteocalcin was associated with higher HbA1c and HOMA-IR（P<0.05），but HOMA-β and AUCINS120/AUCGLU120 ratio showed no association with osteocalcin（P>0.05）.Among the overweight cases（n=187），HbA1c，HOMA-IR，HOMA-β，and AUCINS120/AUCGLU120 ratio demonstrated no association with osteocalcin（P>0.05）.In non-overweight cases（n=142），low osteocalcin was associated with higher HOMA-IR（P<0.05），but HbA1c，HOMA-β and AUCINS120/AUCGLU120 ratio had no association with osteocalcin（P>0.05）.Conclusion　Osteocalcin has a positive regulatory effect on insulin sensitivity and insulin secretion in elderly T2DM patients，which provides a basis for further research on osteocalcin-related hypoglycemic drugs.When combined with subclinical hypothyroidism or overweight，the effect of osteocalcin in regulating glucose metabolism is weakened，which suggests that the impact of subclinical hypothyroidism and overweight on insulin sensitivity should be considered seriously during clinical treatment.

Key words: Diabetes mellitus, type 2；Osteocalcin；Aged；Hypothyroidism；Overweight