Regulation Of Serum Osteocalcin On Glucose Metabolism In Elderly Patients With Type 2 Diabetes Mellitus Complicated With Subclinical Hypothyroidism

Objective:To investigate the changes in the regulation of glucose metabolism by osteocalcin in elderly patients with type 2 diabetes mellitus complicated with subclinical hypothyroidism.Methods:The study enrolled 329 patients with type 2 diabetes over 60 years old who were hospitalized in the First Hospital of Lanzhou University from January 2017to December 2018.Of these,190 patients had normal thyroid function(group A)and139 patients had subclinical hypothyroidism(group B).Fasting blood samples from all patients were collected for determination of TSH,TT4,FT4,OC,25(OH)D,SCr,UA,HCY,HbAlc。All patients were tested for glucose tolerance and insulin release test.The steady-state model insulin secretion index(HOMA-β)was used to reflect the basal insulin secretion function of patients.The ratio of the area under the 0-120 min insulin curve to the area under the 0-120 min blood glucose curve (AUCINS120/AUCGLU120)was used to reflect insulin secretion under sugar loading.The homeostasis model insulin resistance index(HOMA-IR)was used to reflect insulin sensitivity under basal conditions.The insulin sensitivity index(ISI)calculated using the Cederholm formula was used to evaluate insulin sensitivity under sugar loading conditions.The Blood Sugar disposition index(DI)is used to reflect the patient’s ability to dispose blood sugar.Ultrasound-measured right heel bone density was used to screen for osteoporosis.Fundus photography is used to screen for retinopathy.Diabetic nephropathy was screened using the urine microalbumin excretion rate measured by 8-hour urine.Lower extremity Doppler ultrasonography is used to screen for diabetic peripheral neuropathy.Results:1.Compared with group A,the prevalence of coronary atherosclerotic heart disease of group B was increased significantly(P<0.05).Serum osteocalcin levels and Serum25-hydroxyvitamin D levels of the observation group were significantly increased(P<0.01).And HOMA-βwas significantly decreased(P<0.01).2.Binary logistic regression showed that TSH was an independent risk factor for diabetic nephropathy(OR=1.070,P<0.05);there was a significant independent association between TSH levels and osteoporosis in the subjects(OR=0.925,P<0.05).3.Spearman correlation analysis shows that serum thyroid stimulating hormone levels were positively correlated with osteocalcin levels in elderly patients with type 2diabetes(r=0.353,P<0.01).Osteocalcin levels were negatively associated with fasting blood glucose(r=-0.163,P<0.01),postprandial blood glucose(r=-0.179,P<0.01),and glycosylated hemoglobin(HbAlc)(r=-0.132,P<0.05).4.All subjects were divided into 2 groups according to the median osteocalcin level:Low osteocalcin level group(OC1 group)and high osteocalcin level group(OC2 group).Compared with the OC1 group,HOMA-IR(P<0.01)and HbAlc(P<0.05)were significantly decreased in the OC2 group,and ISI and DI were significantly increased(both P<0.01).5.In group A,the above differences between the OC1 subgroup and the OC2 subgroup were significant.While in group B,compared with the OC1 subgroup,the differences in HOMA-IR reduction in the OC2 subgroup was significant(P<0.05),and the above differences in ISI,DI,and HbAlc were not statistically significant(P>0.05).6.In females,compared with OC1 subgroup,HOMA-IR(P<0.05)and HbAlc(P<0.01)were significantly decreased in OC2 subgroup,ISI(P<0.01),HOMA-β(P<0.05),AUCINS120/AUCGLU120(P<0.05)and DI(P<0.01)were all increased.In males,compared with OC1 subgroup,HOMA-IR was significantly decreased in the OC2 subgroup(P<0.01),and ISI was significantly increased(P<0.05).There was no significant difference in HbAlc、HOMA-β、AUCINS120/AUCGLU120 and DI(P>0.05).7.Among the subjects aged 60-75 years,HOMA-IR(P<0.01)and HbAlc(P<0.05)were significantly decreased in the OC2 subgroup compared with the OC1 subgroup,ISI(P<0.01),DI(P<0.05)were significantly increased.The above significant differences disappeared in T2DM patients older than 75 years.8.In the subjects with a body mass index of less than 24kg/m~2,compared with the OC1 subgroup,the HOMA-IR(P<0.01)of the OC2 subgroup was significantly decreased,and the ISI and DI were significantly increased(both P<0.01).In the overweight patients,the above differences have no statistical significance(P>0.05).Conclusion:1.Osteocalcin can increase the body’s sensitivity to insulin in elderly patients with type 2 diabetes,can increase the secretion function of islet β-cells,and can improve the ability to management blood sugar.2.The regulation of osteocalcin on glucose metabolism is attenuated or disappeared in elderly type 2 diabetic patients with subclinical hypothyroidism.3.The regulation of osteocalcin on blood glucose is greatly affected by gender,age and body weight.In elderly women with younger age and a body mass index of less than 24 kg/m~2,osteocalcin has a stronger regulation of blood glucose.4.Serum TSH level is positively correlated with osteocalcin in elderly patients with type 2 diabetes,and osteocalcin level is higher in women than in men.5.TSH is an independent risk factor for diabetic nephropathy in elderly patients with type 2 diabetes.6.As the level of TSH increases,the risk of osteoporosis occurs in elderly patients with type 2 diabetes.