Correlation Of Glucose Fluctuation With Vascular Complications And Pancreatic β Cell Function In Type 2diabetes Mellitus

BackgroundPrevious studies have suggested that intensive glucose control can reduce the risk of vascular complications in early type 2 diabetes patients.And HbA1 c has been confirmed as the gold standard for glycemic control.However,latest studies have shown that vascular complications are not only related to HbA1 c,FPG and PPG,but maybe also to glucose fluctuation.With the progression of type 2 diabetes,the secretion of pancreatic beta cell decreased and insulin resistance increased gradually.That may resulted in elevated glucose fluctuations.So the aims of our study are to investigate the correlation of glucose fluctuation with vascular complications and pancreatic β cell function in type 2 diabetes mellitus.The results from analysis of glucose fluctuation may provide new ideas for clinical treatment of type 2 diabetic patients.Part one: Correlation analysis of glucose fluctuation and macrovascular complications in type 2 diabetes ObjectiveTo investigate the relationship between glucose fluctuation and macrovascular complications in type 2 diabetes mellitus and the risk factors of macrovascular complications.MethodAccording to the carotid intima-media thickness(CIMT)of carotid ultrasonography detection,all patients were divided into non CIMT thicken group(CIMT<0.9mm),mild CIMT thicken group(0.9mm ≤ CIMT < 1.1mm)and severe CIMT thicken group(CIMT≥1.1mm).Patients were divided into macrovascular complications group and non macrovascular complications group according to the clinical data.The general clinical data and laboratory indexes of the subjects were recorded.Continue glucose monitoring(CGM)were performed in both groups.Result1.(1)Compared with non CIMT thicken group,the level of high density lipoprotein cholesterol was lower in severe CIMT thicken group(P<0.05).(2)Compared with non CIMT thicken group and mild CIMT thicken group,the percentage of hyperglycemia,the area under curve(AUC)above 11.1mmol/L,mean blood glucose(MBG),2 hours postprandial glucose(2h PPG)and mean amplitude of postprandial glycemic excursions(MPPGE)were higher in severe CIMT thicken group(all P<0.05).Compared with non CIMT thicken group,the incidence of hypoglycemia were higher in severe CIMT thicken group,glucose fluctuations of standard deviation of blood glucose(SDBG),mean amplitude of glycemic excursions(MAGE),largest amplitude of glycemic excursions(LAGE)were higher in mild CIMT thicken group and severe CIMT thicken group,and glucose fluctuations in severe CIMT thicken group were higher than mild CIMT thicken group(P<0.05).(3)CIMT was positively correlated with the percentage of hyperglycemia,the area under curve(AUC)above 11.1mmol/L,the incidence of hypoglycemia,MBG,2h PPG,MPPGE,SDBG,MAGE,LAGE and negatively with HDL-C.Stepwise logistic regression analyses indicated that MAGE was the risk factors of CIMT.Odds ratio was 1.666(P<0.001).2.(1)Compared with non macrovascular complications group,the patients in macrovascular complications group were older,the duration of DM was longer(all P<0.05).(2)Compared with non macrovascular complications group,the percentage of hyperglycemia,the area under curve(AUC)above 11.1mmol/L,the incidence of hypoglycemia,MBG and 2h PPG were higher in macrovascular complications group(all P<0.05).Glucose fluctuation indexes,such as SDBG,MAGE and LAGE,were higher in macrovascular complications group than in non macrovascular complications group.(3)Macrovascular complications was positively correlated with age,the duration of DM,the percentage of hyperglycemia,the area under curve(AUC)above 11.1mmol/L,the incidence of hypoglycemia,MBG,2h PPG,SDBG,MAGE and LAGE.Stepwise logistic regression analyses indicated that age and MAGE were the risk factors of macrovascular complications.Odds ratio were 1.052 and 1.471 respectively(P<0.001).ConclusionCIMT thickness and macrovascular complications were correlated with the percentage of hyperglycemia,the area under curve(AUC)above 11.1mmol/L,the incidence of hypoglycemia,MBG,2h PPG and glucose fluctuations.There had no remarkable relativity with FPG and Hb A1 c.MAGE was the independent risk factor of CIMT and macrovascular complications.Part two: Correlation analysis of glucose fluctuation with microvascular complications in T2 DM ObjectiveTo investigate the relationship between glucose fluctuation and microvascular complications in T2 DM and the risk factors of microvascular complications.MethodThe patients were divided into DKD group and non-DKD group.The eGFR was estimated by using chronic kidney disease epidemiology collaboration(CKD-EPI)formula.The other experimental methods were similar to the first part.Result(1)Compared with non-DKD group,the patients in DK D group were older,the duration of DM was longer,the ratio of hypertension was higher and the level of high density lipoprotein cholesterol was lower(all P<0.05).Compared with non-DKD group,levels of C ysC,BUN,CRE were higher and eGFR were lower in DKD groups(all P<0.001).It is suggested that DKD can increase the damage of renal function obviously.(2)Glycosylated hemoglobin(Hb A1c),the percentage of hyperglycemia,the area under curve(AUC)above 11.1mmol/L,MBG and 2 h PPG in DKD group were all significantly higher than those in non-DKD group(P<0.05).(3)DK D was positively correlated with age,the duration of DM,hypertension,Hb A1 c,the percentage o f hyperglycemia,the area under curve(AUC)above 11.1mmol/L,MBG,2h PPG and negatively with HDL-C.Stepwise logistic regression analyses indicated that age and HbA1 c were the risk factors of DKD.Odds ratio were 1.048 and 1.569 respectively(P<0.01).ConclusionDKD was correlated with age,the duration of DM,the ratio of hypertension,lower of high density lipoprotein cholesterol and Hb A1 c,MBG,2h PPG,the percentage of hyperglycemia and the area under curve(AUC)above 11.1mmol/L.Age and Hb A1 c were the independent risk factors of DKD.There had no remarkable relatively with glucose fluctuations.Part three: Correlation analysis of glucose fluctuation with pancreatic β cell function ObjectiveTo investigate the relationship between glucose fluctuation and pancreatic β cell function in T2 DM.MethodThe patients were divided into MAGE normal group and MAGE abnormal group according to the levels of MAGE.Oral glucose tolerance test(OGTT)was performed in all patients.Fasting insulin(FINS),fasting C peptide,2h C peptide were recorded,and HOMA-β,HOMA-IR were calculated.Result(1)Compared with MAGE normal group,the level of TC,FPG,Hb A1 c,2h PPG were higher and the level of HOMA-β was lower in MAGE abnormal group(all P<0.05).(2)MAGE was positively correlated with FPG,HbA1 c,2h PPG and negatively with the level of HOMA-β.Stepwise logistic regression analyses indicated that 2 h PPG was positively correlated with MAGE,odds ratio was 1.774(P=0.009),and HOMA-β was negatively correlated with MAGE independently,odds ratio was 0.975(P=0.040).(3)The level of HOMA-β was negatively correlated with FPG,2h PPG,the percentage of hyperglycemia,2h PPG,MBG,SDBG,MAGE and LAGE in spearman correlation analysis(all P<0.05).The multiple linear stepwise regression analysis showed that SDBG was negatively correlated with HOMA-β independently.The level of HOMA-IR was positively correlated with TG,TC,HbA1 c,FPG,the percentage of hyperglycemia,the area under curve(AUC)above 11.1mmol/L,2h PPG and MBG(all P < 0.05).The multiple linear stepwise regression analysis showed that FPG was positively correlated with HOMA-IR independently.ConclusionThe level of MAGE was positively related to FPG,HbA1 c and 2h PPG,and was negatively related to HOMA-β.Furthermore,2h PPG and pancreatic β cell function were independent related to glucose fluctuation.SDBG was negatively related with HOMA-β independently.FPG was positively related with HOMA-IR independently.