Effect Of SGLT2 Inhibitor On Proteinuria,Free Fatty Acid And Metabolite Spectrum In Early Diabetic Kidney Disease

Objective: Through the analysis of the actual clinical data,we understand the effect of SGLT2 inhibitor on proteinuria of type 2 diabetes patients with early diabetic kidney disease in the real world and a series of related changes in the spectrum of free fatty acids and amino acid metabolites in vivo after administration,which provides strong evidence for SGLT2 inhibitor to improve the urinary protein of patients with early diabetic kidney disease in the real world,correct metabolic disorders and prevent related metabolic diseases.Methods:For type 2 diabetes mellitus(in line with WHO diabetes diagnostic criteria)with early diabetic kidney disease(e GFR>45ml/(min*1.73m))admitted to the Endocrine Department of the Second Hospital of Dalian Medical University from June2019 to November 2022,a total of 166 patients treated with SGLT2 inhibitor for 3months or more were analyzed retrospectively.The general clinical data of the patients included age,gender,BMI,medication time and other drug use.Blood biochemical examination results include fasting blood glucose(FPG),fasting insulin,glycosylated hemoglobin(Hb A1c),random urine microalbumin(MA),random urine microalbumin/creatinine(ACR),urea nitrogen(BUN),serum creatinine(Scr),cystatin C(Cys-C),total cholesterol(TC),triglyceride(TG),high-density lipoprotein(HDL-C),low-density lipoprotein(LDL-C),apolipoprotein A(Apo A)Apolipoprotein B(Apo B).31 items of free fatty acid spectrum in blood: capric acid,lauric acid,myristic acid,myristic acid,palmitic acid,palmitic acid,linoleic acid,oleic acid,erucic acid,stearic acid,eicosenoic acid,eicosenoic acid,eicosenoic acid,arachidonic acid,eicosapentaenoic acid,docosahexaenoic acid,docosahexaenoic acid,arachidic acid,arachidonic acid,neuric acid,lignic acid,total omega-3 Total omega-6,omega-3/omega-6,triene/tetraene,total fatty acid,total monounsaturated fatty acid,total polyunsaturated fatty acid,total saturated fatty acid.98 items of genetic metabolic disease screening(amino acid and fatty acid metabolite spectrum).And palmitoleic acid/palmitic acid,insulin resistance index and estimated glomerular filtration rate(e GFR)were calculated.The subjects were type 2 diabetes patients with early diabetic kidney disease.The subjects were randomly divided into two groups according to ACR:group A was a microalbuminuria group(ACR was 30-300mg/g),and group B was a massive proteinuria group(ACR>300mg/g).The changes of proteinuria,fatty acids and amino acid metabolites in early diabetes nephropathy patients after the application of SGLT2 inhibitor were studied.Results: 1、The results of this study showed that after an average of 380 days of SGLT2 inhibitor use,BMI of patients with early diabetic kidney disease decreased(P<0.05),MA significantly alleviated(P=0.031),and ACR also decreased,but the changes of ACR were not statistically significant(P>0.05).In terms of renal function,BUN,Scr and Cys-C increased slightly(P<0.05),while e GFR decreased slightly(P<0.05).In terms of blood glucose,Hb A1 C decreased by 0.81% on average(P<0.05).In terms of blood lipids,the levels of TG and Apo A decreased(P<0.05),while LDL-C and Apo B slightly increased(P<0.05),while the changes of TC and HDL-C were not statistically significant.Among the patients with massive proteinuria(Group B),Hb A1 C,BUN,Scr,Cys-C and e GFR changed more significantly,while the changes of MA and ACR from baseline were not significantly different between the two groups.It is suggested that the effect of SGLT2 inhibitor on improving proteinuria may have nothing to do with the baseline ACR level,and its strong hypoglycemic effect may be better in patients with massive proteinuria.In addition,the simultaneous application of GLP-1RA can better regulate blood lipids.2、In the study on the effect of SGLT2 inhibitor on free fatty acids in patients with early diabetic kidney disease,14 indicators were found to have statistically significant changes(P<0.05): lauric acid,erucic acid,omega-3/omega-6increased from baseline;Myristic acid,palmitic acid,palmitic acid,linoleic acid,oleic acid,stearic acid,eicosotrienic acid,triene/tetraene,total saturated fatty acid,total monounsaturated fatty acid and total fatty acid decreased from baseline.However,the changes of each index compared with the baseline(Δ t)between patients in the two groups of microalbuminuria(group A)and macroalbuminuria(group B),there was no statistical significance in the results of the difference comparison.It is suggested that the effect of SGLT2 inhibitor on free fatty acids in patients with early diabetic kidney disease may not be related to baseline ACR.3、In the study on the effect of SGLT2 inhibitor on amino acid and fatty acid metabolite profiles of early diabetic kidney disease,45 indicators had statistically significant changes(P<0.05),of which 25 indicators were lower than the baseline,including:homocysteine,glutamic acid,glycine,proline,tyrosine,valine,succinylcarnitine,pentenylcarnitine,hydroxymyristoyl carnitine,hydroxypalmitoyl carnitine,eicosyl carnitine,docosacylcarnitine,tetracarbonyl carnitine,Val/He,Cit/Arg,C3/C2,C4/C2,C8/C10,C3DC/C10,C10:2,C14:2,C18:2,C10:2,C10:2,adipic carnitine,(C16+C18)/C10.A total of 20 indicators that are higher than the baseline include: aspartic acid,glutamine,homocysteine,lysine,ornithine,piperonamide,free carnitine,acetylcarnitine,isovalerylcarnitine,caproyl carnitine,octadecanoyl carnitine,26 decanoyl carnitine,Orn/Cit,Phe/Tyr,C3/C16,C16-OH/C16,C18:1,C10:1,(0+2+3+16+18:1)/Cit,C0/(C16+C18).By comparing the differences between groups,we can observe the changes of 8 indicators from the baseline(Δ t)were statistical differences between the two groups,including alanine,propionyl carnitine,palmitoyl carnitine,C3/C0,C3/C2,glutaryl carnitine,C5DC/C5-OH,C5DC/C16.Conclusion: 1、Long term application of SGLT2 inhibitor can significantly alleviate proteinuria excretion,reduce BMI,effectively control blood sugar,and improve dyslipidemia in patients with early diabetic kidney disease.The renal protection of drug may not be related to the initial ACR of treatment,but the hypoglycemic effect of SGLT2 inhibitor may be better in patients with a large number of proteinuria.In addition,combined use of GLP-1RA may have greater benefits in blood lipids.2 、 SGLT2 inhibitor can increase the level of lauric acid and omega-3/omega-6,reduce the level of palmitic acid,stearic acid,total saturated fatty acid and total fatty acid in serum,to improve the metabolic disorder of fatty acid in patients with early diabetic kidney disease,reduce renal inflammatory reaction and lipotoxicity,and prevent related metabolic diseases.The effects of SGLT2 inhibitor on the free fatty acid have beneficial effects on metabolic disorders and delay the progression of kidney disease.3、SGLT2inhibitors have obvious effects on amino acid and fatty acid metabolite profiles.Through in-depth research on the influence of drugs on metabonomics,it is found that relevant biomarkers can evaluate drug efficacy and predict the prognosis of patients with diabetic kidney disease.