Association Of Type 2 Diabetic Vascular Complications With Poor Sleep Complaints And Its Therapeutic Effect

Objective:1.To investigate the association of poor sleep complaints with diabetic vascular complications.2.To explore the significance of advanced glycation end products(AGEs)in the pathogenetic process of sleep complaints in type 2 diabetes patients with cardiovascular disease(CVD).3.To investigate whether individualized diabetes sleep education significantly improve sleep quality and glycemic control in type 2 diabetic patients who sleep after midnight,and protential mechanism by a randomized paralled interventional study.Methods:1.Collecting 1220 participants with type 2 diabetes mellitus who were hospitalized in Metabolic Diseases Hospital of Tianjin Medical University from January 2013 to January 2016.The inclusion criteria for the 1999 WHO Guidelines for the Diagnosis of Type 2 Diabetes.According to the situation of participants with vascular complications into cardiovascular disease(CVD),peripheral arterial disease(PAD),diabetic kidney diseases(DKD),diabetic peripheral neuropathy(DPN)and retinopathy(DR).The poor sleep complaints included difficulty falling asleep,early final awakening,short sleep(<6 hours)and long sleep(>9 hours).A total of demographic data was collected for all patients and a series of physical examinations were performed,including BMI(body mass index)and BP(blood pressure).Biochemical examination indicators based on Hb A1c(glycosylated hemoglobin).All metrological data are expressed as mean ± standard deviation(SD).Classification of variable data using chi-square test to analyze.Multiple regression analysis was used to analyze the relationship between sleep disorders and diabetic vascular complications,and odds ratio(OR)and 95% confidence interval(CI)were used for analysis.Bilateral P <0.05 was considered statistically significant.All data were analyzed using SPSS 18.0.2.Collecting 587 participants with type 2 diabetes mellitus who were hospitalized in Metabolic Diseases Hospital of Tianjin Medical University from June 2013 to June 2015.The inclusion criteria for the 1999 WHO Guidelines for the Diagnosis of Type 2 Diabetes.Guidance for the Diagnosis and Treatment of Cardiovascular Diseases in the Diagnosis and Treatment of the 2014 European Society of Cardiology.Use Pittsburgh Sleep Quality Index(PSQI)to evaluate Participants’ sleep qualities,patients were divided into two groups,one was sleep disorder group(PSQI score≥7,n=241)and the other was non-sleep disorder group(PSQI score<7,n=346).A total of demographic data was collected for all patients and a series of physical examinations were performed,including BMI(body mass index)and BP(blood pressure).Biochemical examination indicators based on AGEs(glycosylation end products).The data of the state distribution are expressed as mean± standard deviation(SD).The non-normal distribution measurement data is expressed as M(P 25,P 75).Classification of variable data using chi-square test to analyze.The data between the two groups were compared by independent sample t test and rank sum test.Row Pearson correlation or Spearman rank correlation.Analysis of Influencing Factors in Logistic Regression Model.Bilateral P <0.05 was considered statistically significant.All data were analyzed using SPSS 18.0.3.Collecting 30 participants with type 2 diabetes mellitus who were hospitalized in Metabolic Diseases Hospital of Tianjin Medical University from February to August in 2014.Patients who sleep after midnight were randomly recruited and allocated to intervention and control group.Patients will receive structured special diabetes sleep education program(intervention group),or conventional diabetes education program with equal time by trained educators.Patients will be followed for 3 months.The main outcome examined was the difference of the changes in Pittsburgh Sleep Quality Index(PSQI)score before and after 3-month intervention between intervention and control group.The other main outcome was the difference of the changes in Hb A1 c between the two groups before and after 3-month intervention.The secondary outcome was the difference of the changes in BP,BMI,HOMA IR,and the differences of the changes in the serum concentrations of FPG,Leptin,Ghrelin,hs CRP,IL-6,TNF-α,Growth hormone,Cortisol between two groups before-after intervention.Pairwise t-test and chi-square test were used to analyze the differences in the parameters between groups.The correlation between serum-related factors and Hb A1 c was investigated by partial correlation and linear regression analysis.Bilateral P <0.05 was considered statistically significant.All data were analyzed using SPSS 18.0.Results:1.Short sleep independently associated with diabetic kidney disease(DKD)(OR>1,P<0.05)after the adjustments,long sleep independently associated with diabetic retinopathy(DR)(OR>1,P <0.05),early final awakening and short sleep independently associated with cardiovascular disease(CVD)(OR>1,P<0.05),short sleep independently associated with peripheral arterial disease(PAD)(OR>1,P<0.05),there was no association between poor sleep complaints and neuropathy(DPN)(P>0.05).2.Compared to non-sleep complaints group,the morbidity of CVD,AGEs and PSQI score were significantly higher in sleep complaints group(P<0.05).PSQI score was positively related to AGEs(rs=0.548,P<0.001),PSQI score was positively related to the morbidity of CVD(rs=0.181,P<0.05),AGEs score was positively related to the morbidity of CVD(rs=0.266,P<0.001).Results of multiple linear regression showed that AGEs increases with the increase of PSQI score(β =0.505,P<0.05).Logistic regression analysis showed the higher PSQI score(OR=1.062,95%CI:1.019-1.119,P=0.005)and elevated AGEs(OR=2.145,95%CI: 1.431-3.214,P<0.001)were risk factors for CVD in T2 DM patients.3.Diabetes sleep education program and conventional control education program(8 courses,280 minutes)were given to provide constructive advices in daily life.Compared with control group,patients in the intervention group get greatly improved their lifestyle.For main outcomes,after diabetes sleep intervention program,PSQI scores were lowered significantly(-1.48±0.88 vs.-0.51±0.71,P<0.001),as well as significant reduction of Hb A1c(-1.5±0.55 vs.-1.11±0.47,P<0.05).FPG and systolic BP were also lowered significantly.HOMA-IR was reduced significantly(-1.29±0.97 vs.1.04±0.91,P<0.01).Serum concentrations for hypersensitivity C-reaction protein,IL-6,cortisol and ghrelin were decreased significantly,with no significance for leptin and growth factor.Partial correlation analysis showed Ghrelin(coefficients-0.65,P<0.001),cortisol(coefficients-0.38,P<0.05)and IL-6(coefficients 0.452,P<0.05)were correlated with the improvement of Hb A1 c.Linear regression analysis showed that the change of Ghrelin was negatively associated with the improvement of Hb A1 c.Conclusion: 1.The study suggests that the poor sleep complaints were distinguishably associated with diabetic vascular complications.2.AGEs is a risk factor for CVD in T2DM patients who with sleep complaints.3.Diabetes Sleep education could improve sleep quality,better blood glucose and BP and decrease insulin resistance via healthier lifestyle.Lower serum concentration of ghrelin might be partly involved in the reduction of Hb A1 c.