Serum Metabolomics And Related Factors In Patients With Diabetic Sarcopenia

Background:Type 2 Diabetes Mellitus(T2DM),as a common endocrine and metabolic disease mainly affecting middle-aged and elderly people,has multiple complications that affect the prognosis and quality of life.Recently,diabetic sarcopenia(DS)has received much attention as a complication of the new T2DM and is a strong predictor of morbidity,disability and death in older adults.T2DM has been shown to promote muscle catabolism by decreasing insulin signaling and increasing insulin resistance,resulting in a rapid loss of muscle strength and mass.The characteristics of diabetic sarcopenia are muscle atrophy,slow nerve conduction,reduced maximum tension produced by skeletal muscle contraction,and slow contraction rate.Therefore,diabetic sarcopenia can cause limb motor degeneration,slow movement,reduced balance,reduced metabolic rate,falls,fractures and so on.The pathogenesis and etiology of diabetic sarcopenia are complex,including insulin resistance,muscle fat accumulation,inflammation,oxidative stress,and lack of exercise,which are very different from sarcopenia caused by other factors.Therefore,it is necessary to develop special diagnosis and treatment criteria for diabetic sarcopenia.In addition,the elderly diabetic population with diabetic sarcopenia should also follow specific therapeutic parameters in the initial and maintenance treatment with hypoglycemic drugs and insulin.However,there is no specific serum metabolite to guide diagnosis and improve prognosis.Therefore,based on serum metabolomics technology,we analyzed the serum metabolites of DS and its pathogenesis at the level of metabolites,and explored the role of serum metabolites in disease diagnosis,intervention and treatment from the perspective of metabolites.Objectives:(1)To explore the risk factors in patients with diabetes and diabetic sarcopenia,and analyze the correlation between the risk factors and serum biomarkers;(2)To explore potential serum biomarkers of diabetic sarcopenia and analyze its value in early diagnosis and treatment.Subjects and methods:A total of 280 patients with type 2 diabetes mellitus(n=39 patients with sarcopenia[DS],n=241 patients without sarcopenia[DM])were enrolled in the Geriatric Medicine Department of Qilu Hospital of Shandong University.Relevant clinical data and laboratory results were collected,and fasting serum was retained.The sera of 10 patients were randomly selected from the two groups.Non-targeted metabolomics analysis was performed by high performance liquid chromatography-electrospray ionization tandem mass spectrometry.Finally,the results of metabolomics were verified in the sera of 280 patients.Results:(1)No significant differences were observed in sex,however,significant differences were detected in muscle mass(P<0.05),grip strength(P<0.01),and calf/waist/hip circumference(P<0.05)between the DS and DM groups.Moreover,compared with the DM control group,DS patients were older and had a longer course of T2DM(P<0.05).DS patients also had lower BMI and DBP,as well as higher pulse pressure(P<0.05),serum triglyceride concentrations,plasma glucose,and glycosylated hemoglobin levels(P<0.05 for each).Moreover,serum HDL levels were lower in DS patients compared with those in the DM controls(P<0.05).Meanwhile,no significant differences were observed in uric acid concentration.(2)632 different metabolites were identified,82 of which were significantly different(P<0.05,VIP>1,FC>1.2 or FC<0.8).Compared with DM group,the contents of pentadecanoic acid,5’-Methylthioadenosine(5’-MTA),N,N-Dimethylarginine(ADMA)and glutamine in DS group are significantly increased,while the contents of isoxanthohumol are decreased.Therefore,pentacanoic acid,5 ’-MTA,ADMA,and glutamine may be potential biomarkers for diabetic sarcopenia based on the subject’s operating characteristic curve analysis.(3)By KEGG pathway analysis,ATP-binding box(ABC)transporter(P<0.05)and mammalian target of rapamycin(mTOR)signaling pathway(P<0.05)were the most significant differences between DS and DM groups.Conclusion:In this study,it was found that aging,elevated fasting blood glucose,and elevated 5’-MTA and ADMA concentrations were independent risk factors for diabetic sarcopenia,which had guiding significance for early screening and diagnosis of diabetic sarcopenia patients.This study explored potential serum biomarkers of diabetic sarcopenia using metabonomics.This study suggests that pentacanoic acid,5 ’-MTA,ADMA,and glutamine are considered potential biomarkers for diabetic sarcopenia,and that ABC transporters and mTOR signaling pathways may contribute significantly to the development of diabetic sarcopenia.