Study On The Association Between Long-term Blood Glucose Variability And The Risk Of Death From All-cause And Major Causes Of Death In People With Type 2 Diabetes

ObjectivesDiabetes is a metabolic disorder characterized by elevated blood sugar levels,insulin resistance,and insufficient insulin secretion.Diabetes,which is one of the main reasons for early death of diabetic patients,easily leads to the occurrence and development of various complications and increases the risk of death.As a chronic non-communicable disease,diabetes has a long course of disease and is difficult to cure.With the prevalence of diabetes increasing,it has imposed a heavy economic burden on the country’s health system and seriously affected the life quality of diabetic patients.This study analyzed the association between long-term blood glucose variability and allcause mortality,cardiovascular disease mortality and cancer mortality in patients with type 2 diabetes.The baseline data of patients with type 2 diabetes in the community of Changshu City,Jiangsu Province in 2013,the follow-up data in 2020,and the physical examination data of the elderly in Changshu City from 2014 to 2019 was analyzed to improve diabetes blood glucose control program.Methods1.In 2013,the research team conducted a detailed epidemiological survey on 10246 patients with type 2 diabetes who were included in the follow-up management of the national basic public health services in Changshu.We relied on basic public health services to carry out an active followup survey,and update their fasting plasma glucose in time.The information of the subjects’ death status was obtained from the Jiangsu Death Cause Monitoring System by matching ID card information.Finally a 2013-2020 survey target research database was established.2.After excluding the survey subjects with less than 3 times blood glucose records or missing important covariates,the data of 7174 patients with type 2 diabetes was finally studied.The blood glucose variability indicators: average real variability(ARV),coefficient of variation(CV)and variability independent of mean(VIM)were calculated and their quartiles were used to divide the subjects into four groups(Q1,Q2,Q3,Q4)which were the basements of describing the baseline characteristics.Continuous variables were compared by t-test or one-way analysis of variance,and categorical variables were compared by the chi-square test.3.7174 patients with type 2 diabetes were included in the study,Cox proportional hazards regression models was used to analyze the association between long-term blood glucose variability and the risk of death from all causes,cardiovascular disease and malignant tumors.Subgroup analysis of age,gender,oral hypoglycemic drugs and insulin use groups were performed.Subjects with coronary heart disease and stroke at baseline were excluded for sensitivity analysis to ensure the stability of the results.Results1.A total of 7174 patients with type 2 diabetes were included in this analysis,including 2486 males and 4688 females,with an average age of(64.93±7.83)years.The baseline FPG level was(8.71±2.59)mmol/L,the male baseline FPG level was(8.89±2.68)mmol/L,and the female baseline FPG level was(8.61±2.53)mmol/L.When ARV was used as the grouping variable,there were statistically significant differences in age,proportion of males,education level,smoking,leisure exercise,BMI,diabetes course,oral hypoglycemic drugs and insulin use among different blood glucose variants(P<0.05).When CV was used as a grouping variable,differences were statistically significant on the age,proportion of males,education level,smoking,leisure exercise,BMI,diabetes course,oral hypoglycemic drugs,insulin use,hypertension,coronary heart disease,and stroke among different blood glucose variants(P<0.05).When VIM was used as the grouping variable,age,proportion of males,education level,smoking,drinking,diabetes course,oral hypoglycemic drugs,insulin use,and hypertension were statistically significant among different blood glucose variations(P<0.05).2.The cumulative follow-up was 48941.16 person-years,males were followed up for 16,786.98person-years,and females were followed up for 32,154.18 person-years,with an average follow-up of 6.82 years.As of December 31,2020,there were 699 deaths from all causes,with a death density of 1428 per 100,000 person-years,including 230 deaths from CVD and 166 deaths from malignant tumors.The average age,proportion of men who died from all causes,education level of elementary school and below,proportion of people who never exercise,diabetes course,proportion of insulin use,proportion of hypertension,proportion of coronary heart disease,and proportion of stroke were higher than those of survivors.BMI level and abnormal blood lipid ratio were lower than those of survivors(P<0.05).There were statistically significant differences in age,male,educational level,BMI,diabetes course,oral hypoglycemic drugs,insulin use,hypertension,dyslipidemia,coronary heart disease,and stroke among the CVD death population,non-CVD death population,and surviving population.Among the three populations of survival,tumor death and non-tumor death,differences in age,proportion of males,education level,leisure exercise,BMI,diabetes course,insulin use,and history of major diseases(hypertension,dyslipidemia,coronary heart disease,stroke)were statistically significant(P<0.05).3.The multi-factor adjusted Cox regression proportional hazard model analysis showed that the long-term blood glucose variability indicators ARV,CV,and VIM all showed that the long-term blood glucose variability was a risk factor for death from all causes.Compared with the respective lowest quartile,the risk of death from all causes in the highest quartile of blood glucose ARV was 1.47 times than that of the lowest quartile(95%CI: 1.16-1.86).The risk of death from all causes in the highest quartile of CV was 2.02 times that of the lowest quartile(95%CI: 1.62-2.52).The risk of death from all causes in the highest quartile of VIM was 1.55 times that of the lowest quartile(95% CI: 1.23-1.95).4.The results of multivariate adjusted Cox regression proportional hazards model analysis showed that compared with the lowest quartile of CV and VIM,the risk of CVD death in the highest quartile of long-term blood glucose variability was significantly increased,with HR values of 1.67(95 %CI: 1.14-2.45)and 1.43(95%CI: 1.00-2.10).The HR value of blood glucose ARV and CVD death risk was 1.33(95%CI: 0.91-1.95),and no statistically significant association between the two was found(P>0.05).5.The multi-factor adjusted Cox regression proportional hazard model analysis showed that the results of Cox regression analysis showed that the HR of ARV and VIM were 0.89(95% CI: 0.56-1.42),1.29(95% CI: 0.81-2.07).It was not found that the risk of death from malignant tumors in the highest quartile group was statistically significant compared with that in the lowest quartile(P>0.05).The risk of death from malignant tumors in the highest quartile of CV was 1.61 times that of the lowest quartile(95% CI: 1.06-2.46).ConclusionLong-term blood glucose variation is an independent risk factor for all-cause mortality,cardiovascular mortality and malignant tumor mortality.High-level long-term blood glucose variation can increase the risk of all-cause mortality,cardiovascular mortality and malignant tumor mortality in patients with type 2 diabetes.In the treatment and management of type 2 diabetes,in addition to paying attention to the level of blood glucose,attention should be paid to the variation of blood glucose at the same time,and the monitoring of blood glucose control in type 2 diabetes patients should be strengthened to ensure stable and safe blood sugar reduction,so that the risk of mortality in type 2 diabetes patients can be reduced.