Evaluate And Research At An Early Stage On Insulin Resistance In Middle-aged And Elderly People

Background:Insulin resistance（IR）already existed before the onset of type 2diabetes（T2DM）.T2DM is the consequence of the gradual progress of IR and runs through T2DM all the time.At present,there is a lack of research and data on IR degree,pathological changes,diagnostic cut-off point value,etc.before diabetes.Early evaluation and research is beneficial to intervene in the progression of IR to T2DM before the occurrence of diabetes.Objective:This project conducts early evaluation and research of IR for middle-aged and elderly people who have no diabetes diagnosis experience,and explores the characteristics,degree and diagnostic cut-off value point of IR be fore（or early）diabetes occurs.Methods:From October 2020 to December 2022,this project conducted recruitment and research on IR for non-diabetic middle-aged and elderly people in the outpatient clinics,wards and physical examination centers of the Department of Geriatrics and General Medicine of the First Affiliated Hospital of Hainan Medical College.Age over 40 and under 80 years of age at enrollment,FPG<7.0mmol/L.The family and myself confirm that there is no history of diabetes and diabetes symptoms,and no diabetes has been diagnosed at any time or place.After recruitment,a total of 73 subjects were included,excluding incomplete data,incomplete information,and withdrawal.Finally,60 eligible subjects were adopted.Collect their medical history and general information,and calculate their body mass index（BMI）.Detect routine biochemical items such as liver and kidney function and glycated hemoglobin.Conduct OGTT and insulin secretion tests,C-peptide secretion tests,etc.Evaluate the biochemical changes in glucose,lipid metabolism,and other functions of the subjects,βCellular function HOMA-β、Analyze the correlation between early changes such as△I₃₀/△G₃₀,△I₁₂₀/△G₁₂₀,and IR.Divide the subjects into a high HOMA-IR index group（HIR）and a low HOMA-IR index group（LIR）with a median HOMA-IR value of 1.77 as the segmentation point,and compare the glucose and lipid metabolism of the two groupsβCellular function HOMA-β、Differences such as△I₁₂₀/△G₁₂₀.In the LIR group,the HOMA-IR-P₂₅cutoff point value of 1.23 was used as the segmentation point,and they were divided into a large P₂₅group and a small P₂₅group.The changes in IR levels such as glucose and lipid metabolism were compared between the two groups.Conduct statistical analysis of the correlation between the four IR evaluation models.The combination of steady-state model insulin resistance index HOMA-IR,quantitative insulin sensitivity detection index QUICK,dynamic insulin sensitivity index Matsuda,and insulin sensitivity index Gutt was used to evaluate IR.The obtained model values of the subjects were described and counted for data distribution,and the quartile distribution was compared with the diagnostic cut-off point value recommended by the Chinese Medical Association and other data at home and abroad.The early IR characteristics and diagnostic cut-off point value of the project subjects were proposed.Each IR evaluation model adopts internationally recognized calculation formulas.SPSS26.0 is used as the statistical software of this project to describe normal distribution data with mean and standard deviation（x±s）,and non normal distribution data with median and interquartile spacing M（Q）.The differences between the two groups were compared using chi square test and Mann Whitney U test,and the correlation analysis was conducted using Kendalls tau-b correlation analysis.A P<0.05 was considered statistically significant.Results:After research,the median age of the subjects was 63 years old and the median BMI was 25.71.NGT 18 cases accounted for 30%;Pre DM（including IFG+IGT）accounted for 51.67%;Eleven patients（FPG<7.0 mmol/L at enrollment,postprandial blood glucose>11.1 mmol/L,diabetes mellitus not excluded）were not excluded from DM（see Table 1,see Figure 1）.It was suggested that 70%of subjects in this project had abnormal glucose metabolism,that is,IR.Thereinto:（1）BMI and ALT are all correlated or significantly correlated with the four indexes HOMA-IR,QUICK,Matsuda,and gutt（positively correlated with HOMA-IR,negatively correlated with others,P<0.05 or P<0.01）,that is,the larger the BMI and ALT values,the heavier the degree of IR;TG is associated with HOMA-IR,QUICK,Matsuda（positively correlated with HOMA-IR,negatively correlated with others,P<0.05 or P<0.01）,the greater the TG value,the heavier the degree of IR;FPG,2h PG have no correlation with HOMA-IR,QUICK,Matsuda,and are negatively correlated with Gutt P<0.01.βcell function indexes FIns,INS_120,△I₁₂₀/△G₁₂₀,ACUI/AUCG,etc.were all related or significantly correlated with HOMA-IR,QUICK,Matsuda,Gutt（positively correlated with HOMA-IR,negatively correlated with other P<0.05 or P<0.01）,and insulin production index△I₃₀/△G₃₀did not show correlation with HOMA-IR,QUICK,GUTT.That is,the early stage of IR is mainly related to the increase of basal insulin secretion and late phase insulin secretion,△I₁₂₀/△G₁₂₀,ACUI/AUCG increase,andβcell function is enhanced.（See tables 2,3）.Other biochemical projects TC,LDL-C,U,etc.were not correlated with IR（P>0.05,see Table 2）.（2）The four evaluation model indices HOMA-IR were significantly negatively correlated with QUICK,Matsuda and Gutt indices（P<0.01）,that is,the larger the HOMA-IR value,the heavier the IR degree,while the smaller the QUICK,Matsuda and Gutt values,the heavier the IR degree（see Figure 2）.（3）Comparing the HIR group and LIR group,there was no difference in the number of non excluded cases of NGT,Pre DM,and DM between the two groups（P>0.05,see Figure 1）;There was no statistically significant difference in age,FPG,2h PG,△I₃₀/△G₃₀（P>0.05,see Table 4）,βCellular functional indicators HOMA-β、There were significant differences between the two groups,△I₁₂₀/△G₁₂₀,and AUCI/AUCG.The HIR group was significantly higher than the LIR group（P<0.01,see Table 4）.In the LIR group with HOMA-IR<1.77,there were 8 cases of NGT,and a total of22 cases with Pre DM+DM not excluded.There were still 73.3%of IR patients（see Figure 1）,so the cutoff value for IR diagnosis should be HOMA-IR<1.77.There was a statistical difference in BMI and TG between the two groups（P<0.05 or P<0.01）;The higher the HOMA-IR value,the higher the BMI and TG values,βEnhanced cell function.（4）Comparing the large P₂₅group with the small P₂₅group:There was no statistically significant difference in the number of pre DM+DM cases between the two groups（P>0.05,see Figure 3）.13 cases of Pre DM+DM were not excluded in the large P₂₅group,accounting for 86%（see Figure 3）.The four subjects corresponding to the P₂₅point(or P₇₅)of the four index model were overweight,high triglyceride,and IFG patients,respectively;Overweight and DM patients were not excluded;Overweight and IGT patients;IFG+IGT patients（see Table 5）.It suggests that the cutoff point value for IR diagnosis in this group of subjects may extend to P₂₅（HOMA-IR）or P₇₅（QUICK,Matsuda,Gutt）.Conclusion:About 70%of the middle-aged and elderly people in this project develop IR before or at the early stage of diabetes.IR is significantly and positively correlated with abnormal lipid metabolism and increased insulin secretion,which is manifested by increased TG,weight and ALT,increased fasting insulin secretion,increased late phase insulin secretion,and increased△I₁₂₀/△G₁₂₀,ACUI/AUCG,and increased isletsβEnhanced cell function.The cut point value of IR diagnosis is less than the median value,and even the quartile HOMA-IR(P₂₅)1.23,QUICKI(P₇₅)0.37,Matsuda(P₇₅)125.40,Gutt(P₇₅)72.12 conform to the cut point value of IR diagnosis of this subject population.