| Objective:Currently,according to a 2020 report published in BMJ,the prevalence of diabetes adults is 12.8%in China.Type 2 diabetes mellitus(T2DM)is attributable to microvascular and macrovascular complications,and increases the risk of death.All-cause mortality was significantly higher in persons with diabeties than in persons without diabeties,it is estimated that diabetes contributes to 11.3%of deaths globally among adults aged 20-79 years.Muscle is the largest organ of glucose metabolism in human body.According to previous studies,the complications of T2DM,such as diabetic macrovascular disease,diabetic microvascular disease,diabetic neuropathy and diabetic nephropathy,are closely related to the quantity,quality and distribution of muscle,and the muscle mass of T2DM patients is lower than that of persons without diabeties,and loss of muscle mass in patients with T2DM is associated with adverse health outcomes such as death,but the effect of lean mass distribution on mortality among patients with T2DM remains obscure.The purpose of this study was to evaluate the relationship between lean body mass distribution and the risk of all-cause mortality in patients with T2DM.Methods:1.Data from 4,562 consecutive inpatient records with type 2 diabetes,one of the diagnoses at discharge from the Department of Endocrinology and Metabolic Diseases,Tianjin Medical University General Hospital between June 2013 and May 2018,were retrieved.The present study finally included 2,335 uique adults with type 2 diabetes after deduplicating for repeated hospitalization,and after excluding patients who met exclusion criteria and incomplete clinical data.2.Patients’ information on date of birth,sex,insurance types,blood pressure,body mass index(BMI),age of diabetes diagnosis,family history of diabetes,history of chronic disease,smoking status,current alcohol consumption,and medication prescriptions such as antihypertensive drugs,glucose-lowering drugs,lipid-lowering drugs,and height,glycated hemoglobin Alc(HbAlc),serum low-density lipoprotein(LDL)cholesterol,glomerular filtration rate(eGFR),total lean mass and regional lean mass.Follow-up data were collected,the surveys were followed to the end of July 1st 2020 or patients’ death,whichever occurred first.3.Total,truncal,leg,arm,android(the regions of interest for male morphology)and gynoid(the regions of interest for female morphology)were assessed by dual energy X-ray absorptiometry(DEXA)using a Prodigy-GE densitometer and a software provided by the manufacturer with the regions of interest(ROI)defined accordingly during hospital admission.Android-to-gynoid lean mass ratio was calculated as android lean mass divided by gynoid lean mass and was a marker to assess the distribution of lean mass.4.Differences in risk factors were tested using chi-square tests for categorical variables and student t test or ANOVA for continuous variables.Cox proportional hazards regressions were used to estimate effects of lean mass distribution on the risk of all-cause mortality.In the model,factors that might influence mortality risk were adjusted,all analyses were adjusted for age and sex(Model 1),additionally for insurance status,smoking,and alcohol drinking(Model 2),then for systolic blood pressure,HbAlc,eGFR,LDL cholesterol,history of cardiovascular disease(CVD),use of antiplatelet agents,antihypertensive drugs,glucose-lowering agents,and cholesterol-lowering agents(Model 3),and further for BMI(Model 4).The analysis for the association of android-to-gynoid lean mass ratio with the risk of all-cause mortality was adjusted for leg lean mass(Model 5).The restricted cubic spline nested in time-dependent Cox models was conducted to test whether there was a dose-response or nonlinear association of android-to-gynoid lean mass ratio as a continuous variable with the risk of all-cause mortality.All analyses were performed with R,version 3.5.3,and SAS for Windows,version 9.4(SAS Institute,Inc,Cary,NC).P<0.05 was considered statistically significant.Results:1.The average age of the patients was 58 years at baseline and 51.4%of patients were women.Descriptive characteristics of the study population at baseline are presented:Age,duration of diabetes,android-to-gynoid lean mass ratio,LDL-C,the number of people taking antihypertensive drugs were significantly higher in women comparing with men,while the proportion of total lean mass,trunk lean mass,leg lean mass,arm lean mass,android lean mass,gynoid lean mass,diastolic blood pressure,current smoking and alcohol consumption were significantly lower in women comparing with men.Age,BMI,duration of diabetes,systolic blood pressure,truncal,and android lean mass,HbAlc,proportion of patients having insurance,using antihypertensive,lipid-lowering,anti-platelet,and oral glucose-lowering medications,and proportion of patients using insulin increased across tertiles of android-to-gynoid lean mass ratio,while total,leg,arm,and gynoid lean mass,and proportion of alcohol drinkers decreased across tertiles of android-to-gynoid lean mass ratio.2.During a median follow-up of 4.31 years[IQR,3.12-5.72 years]),128 patients died.The multivariable-adjusted(Model 4)hazards ratios(HR)of all-cause mortality across the tertiles of leg lean mass were 1.00,0.52,and 0.31(P for trend=0.004),respectively,for each standard deviation(SD)increase in leg lean mass,the risk of all-cause death decreased by 46%(HR 0.54[95%confidence interval(CI),0.36-0.80),while there were no associations of total,truncal,arm,android and gynoid lean mass with the risk of all-cause mortality.3.The multivariable-adjusted(Model 4)HR of all-cause mortality across the tertiles of leg lean mass werel.00,1.88,and 3.01(P for trend<0.001),respectively,for each SD increase in android-to-gynoid lean mass ratio,the risk of all-cause death increased by 52%(HR 1.52[95%CI,1.31-1.77]).After further adjustment for leg lean mass,this positive association of android-to-gynoid lean mass ratio with the risk of all-cause mortality was still significant(P for trend=0.001).When android-togynoid lean mass ratio was examined as a continuous variable by using RCS,a positive association of android-to-gynoid lean mass ratio with the risk of all-cause mortality was observed.4.Sensitive analysis,after excluding subjects who died during the first 1 years of follow-up(n=7),the positive association between android-to-gynoid lean mass ratio and all-cause mortality did not change,the multivariable-adjusted(Model 4)HR of all-cause mortality across the tertiles of android-to-gynoid lean mass ratio were 1.00,1.78,and 2.68(P for trend<0.001)respectively,for each SD increase in android-to-gynoid lean mass ratio,the risk of all-cause death increased by 46%(HR 1.46[95%CI,1.25-1.70]).5.Adjusting for age and sex insurance status,smoking and alcohol consumption,this positive association between android-to-gynoid lean mass ratio and the risk of all-cause was still present among patients of different ages,BMI and HbAlc levels,never smokers,men,and patients using insulin.Significant interactions of android-to-gynoid lean mass ratio and sex(P for interaction<0.025)with the risk of all-cause mortality were observed,while there were no significant interactions of android-to-gynoid lean mass ratio and age,smoking,BMI,HbAlc,and use of insulin with the risk of all-cause mortality.Conclusion:1.The android-to-gynoid lean mass ratio was associated with an increased risk of all-cause mortality in patients with T2DM.2.Lower leg lean mass,assessed by DEXA,was inversely associated with the risk of all-cause mortality among patients with type 2 diabetes,while there were no associations of total lean mass,truncal lean mass,arm lean mass,android lean mass and gynoid lean mass with the risk of all-cause mortality.3.There was positive association between android-to-gynoid lean mass ratio and the risk of all-cause was still present among patients of different ages,BMI and HbAlc levels,never smokers,men,and patients using insulin.Significant interactions of android-to-gynoid lean mass ratio and sex with the risk of all-cause mortality were observed. |
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