Correlation Between Blood Glucose Fluctuation,TIR And Bone Metabolism In Type 2 Diabetic Patients

Objective:Patients with type 2 diabetes mellitus(T2DM)were studied,fingertip blood glucose monitoring was performed at 7 points for 3 consecutive days using self-blood glucose test(SMBG),blood glucose excursion values SDBG,PPGE,LAGE,and time within the glucose target range(TIR)were calculated,bone metabolism parameters osteocalcin(OCN),N-terminal propeptide of type I procollagen(P1NP),cross-linked C-terminal peptide of type I collagen(β-CTX),parathyroid hormone(PTH),and serum 25(OH)D were measured,the correlation between bone metabolism and blood glucose excursion and TIR was analyzed,and the effects of blood glucose excursion and TIR on bone metabolism in T2DM patients were investigated.Methods:A total of 398 T2DM patients with complete data who were hospitalized in the Department of Endocrinology of the Second Hospital of Shanxi Medical University from October 2019 to October 2021 were selected as the screening subjects and met the WHO1999 diagnostic criteria for diabetes and the 1994 diagnostic criteria for osteoporosis.The ineligible patients were excluded according to the inclusion/exclusion criteria,and 204patients were selected as the study subjects.General data were collected from all study subjects to detect blood biochemical indicators:glycosylated hemoglobin(Hb A1c),triglyceride(TG),total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL),OCN,P1NP,β-CTX,PTH,serum 25(OH)D;blood glucose fluctuation indicators were calculated from fingertip blood glucose values measured before and after three meals and at 7 o’clock before bedtime within 24 hours:mean blood glucose standard deviation(SDBG),amplitude of blood glucose fluctuation(PPGE),maximum amplitude of blood glucose fluctuation(LAGE),and TIR and TAR were also calculated;bone mineral density was measured with dual-energy X-ray absorptiometry.Study grouping method:(1)According to the level of blood glucose fluctuation,the patients were divided into blood glucose stable blood glucose fluctuation group;(2)According to the T/Z score detected by DXA,the patients were divided into normal bone mass,osteopenia and osteoporosis groups;(3)According to the TIR level,the patients were divided into four groups:TIR≤51%group,TIR(51%～71%)group,TIR(71%～86%)group and TIR≥86%group.Changes in blood glucose fluctuations,TIR,and bone metabolism parameters between study groups were analyzed to analyze the correlation between blood glucose fluctuations and diabetic osteoporosis.Results:1.General clinical characteristics of blood glucose stabilization group:Among 204patients with type 2 diabetes collected in this study,114 patients(65 males and 16 females)were in blood glucose stabilization group,with mean age of(58.88±11.73)years and BMI of(24.86±3.09)kg/m~2;90 patients(44 males and 46 females)were in blood glucose fluctuation group,with mean age of(61.34±12.57)years and BMI of(24.52±3.81)kg/m2.There was no statistically significant difference in age or BMI between the two groups(P>0.05),which were comparable.There were significant differences in gender,Hb A1c,SDBG,PPGE,LAGE,β-CTX and P1NP between patients with stable blood glucose and those with blood glucose fluctuation(P<0.05).There was no significant difference in TG,TC,HDL,and LDL between the two groups(P>0.05).2.Comparison of analysis of different TIR groups:With the gradual increase of TIR values,the values of SDBG,PPGE,LAGE,and TAR gradually decreased,and the difference was statistically significant(P<0.001),and the P1NP values in the TIR≥86%group were significantly higher than those in the other three groups,and the difference was statistically significant(P<0.001).The TIR groups varied in different bone mineral density groups,and the proportion of TIR≤51%was significantly higher in osteoporotic patients(44.1%)than in normal bone mass(35.3%)and osteopenia groups(20.6%),and the proportion of TIR≥86%was significantly higher in normal bone mass group(55.9%)than in osteopenia group(18.6%)and osteoporosis group(25.4%),and the differences were statistically significant(P<0.001).3.Grouped according to bone density,SDBG,PPGE and LAGE comparison:SDBG,PPGE and LAGE in patients with different bone mass groups were the same(P<0.001),and SDBG,PPGE and LAGE values in patients with osteopenia and osteoporosis were higher than those in patients with normal bone mass,and the differences were statistically significant;There was no difference in SDBG,PPGE,and LAGE values between patients with osteopenia and osteoporosis(P>0.05).4.Correlation Analysis of blood glucose excursion,TIR and bone metabolism:β-CTX was positively correlated with SDBG,PPGE and LAGE(r=0.246,P<0.001;r=0.261,P<0.001;r=0.227,P=0.001);P1NP was negatively correlated with SDBG,PPGE and LAGE(r=-0.264,P<0.001;r=-0.254,P<0.001;r=-0.259,P<0.001)and TIR(r=0.168,P=0.012);serum 25(OH)D was negatively correlated with SDBG,PPGE and LAGE(r=-0.166,P=0.013;r=-0.171,P=0.010;r=-0.145,P=0.030)and positively correlated with TIR(r=-0.155,P=0.020);PTH and OCN were not correlated with SDBG,PPGE,LAGE and TIR levels(P>0.05).5.Results of multivariate logistic regression analysis of TIR and bone mineral density:After adjusting for the effects of gender,age,BMI,and blood lipids using the normal bone mass group as a reference,the results of multivariate logistic regression analysis showed that for each group of TIR increase,the risk of osteoporosis in patients was reduced by 28.7%,and the difference was statistically significant(OR=0.731,P=0.032),suggesting that TIR may be a protective factor for diabetic osteoporosis(DOP).In addition,age,gender,BMI,and serum triglycerides were associated with DOP in the osteoporotic group,and the difference was statistically significant(P<0.05);among them,age and serum triglycerides were risk factors for DOP(OR=1.088,OR=1.328),and BMI was a protective factor for DOP(OR=0.875).Conclusion:1.Blood glucose fluctuation is closely related to bone metabolism status in patients with type 2 diabetes,as shown by the positive correlation between blood glucose fluctuation indicators SDBG,PPGE,and LAGE and bone resorption markerβ-CTX,and negative correlation with bone formation indicator P1NP.With the increase of blood glucose fluctuation amplitude,β-CTX level increases,bone resorption increases,P1NP level decreases,and bone formation decreases.Therefore,blood glucose fluctuation may be one of the risk factors of diabetic osteoporosis.2.According to the TIR quartile groups(≤51%,51%～71%,71%～86%,≤86%),for each TIR increase in type 2 diabetic patients,the risk of osteoporosis was reduced by28.7%;when TIR≥86%,the blood glucose fluctuation was significantly reduced,and the risk of osteoporosis was significantly reduced,indicating that TIR is a protective factor for the occurrence of diabetic osteoporosis.