The Correlation Between C1q/Tumor Necrosis Factor-related Protein-6 And The Development Of Different Glucose Tolerance

PART ? LEVELS OF PLASMA CTRP6 LEVELS IN PEOPLE WITH DIFFERENT LEVELS OF INSULIN RESISTANCEObjective:To determine the roles of plasma CTRP6 in the development of insulin resistance by measuring plasma CTRP6 levels in healthy people,impaired glucose tolerance and newly diagnosed type 2 diabetes mellitus.Methods: According to the WHO Diabetes Diagnosis Guideline,118 patients with newly diagnosed T2 DM,98 impaired glucose tolerant(IGT)and 132 healthy subjects were recruited for this study.After a 10-12 hour overnight fast,all individuals participated in the series of anthropometric and body composition examination.BMI,waist circumference(WC)and hip circumference were examined.The waist-to-hip ratio(WHR)was calculated by the same observer.An analyzer of bioelectrical impedance was used to measure the percentage of body fat(FAT%).Plasma TG,TC,HDL-C,and LDL-C were detected by enzyme coupling rate method,plasma glucose was detected by glucose oxidase method,and hemoglobin A1 C was measured by ion exchange high performance liquid chromatography.Serum insulin was measured with electrochemiluminescence.The homoeostasis model assessment of insulin resistance(HOMA-IR)was calculated using the following equations: HOMA-IR = [fasting insulin(FINS,mu/L)× fasting blood glucose(FBG,mmol/L)] / 22.5.Plasma CTRP6,TNF-? and adiponectin levels were detected by enzyme-linked immunosorbent assay according to manufacturer's protocol.Results: In IGT and T2 DM individuals,BMI,FAT(%),WHR,triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),Hb A1 c,FBG,2-hour blood glucose after glucose overload(2h PG),FIns,2-h plasma insulin after glucose overload(2h INS),and HOMA-IR were significantly increased relative to the healthy subjects(P <0.05 or P <0.01).Moreover,in T2 DM patients,high-density lipoprotein cholesterol(HDL-C)was significantly decreased as compared with healthy and IGT subjects(P <0.05 or P <0.01).No difference was found in circulating CTRP6 between male and female in the healthy subjects.Importantly,circulating CTRP6 concentrations were significantly increased in both IGT subjects and T2DM patients compared with normal individuals,whereas circulating CTRP6 levels were further increased in T2 DM patients relative to IGT subjects(both P <0.01).Furthermore,circulation adiponectin concentrations were markedly decreased in IGT and T2 DM individuals compared with healthy subjects,whereas in patients with T2 DM,adiponectin levels were lower than IGT groups(all P <0.01).Similar to circulating CTRP6,serum TNF-? concentrations were markedly increased in T2 DM patients relative to IGT and healthy controls(P <0.05 or P <0.01).Conclusion: The plasma CTRP6 is significantly elevated in type 2 diabetes and overweight/obesity people.CTRP6 is closely related to insulin resistance and plays an important role in the development of insulin resistance.PART ? THE RELATIONSHIP BETWEEN PLASMA CTRP6 AND TYPE 2 DIABETES MELLITUSObjective: To determine the relationship between plasma CTRP6 and insulin resistance and type 2 diabetes mellitus by analyzing the correlation of plasma CTRP6 with clinical and biochemical parameters in human.Methods: SPSS version 20.0 was used for all statistical analyses.The association of CTRP6 with other variables was determined by simple correlation test by controlling the covariates.Multiple linear regression analyses were used to analyze variables that had independent associations with CTRP6 and those with possible biological relevance.Multiple stepwise regression analyses were used to assess the independently associated factors in all subjects participated in the study.The association of CTRP6 with IGT and T2 DM was examined by binary logistic regression analysis.The utility of circulating CTRP6 levels to determine IGT,IR and T2 DM was evaluated by receiver operating characteristic(ROC)curve analysis.Results: In bivariate correlation analyses,serum CTRP6 concentrations were correlated positively with BMI,FAT%,TC,TG,Hb A1 c,FBG,2h PG FINS,HOMA-IR and TNF-?,whereas negatively with HDL-C and Adipoq in all study individuals(P <0.05 or P <0.01 or P <0.001).Multiple regression analysis displayed that Hb A1 c,TG and TNF-? were independent influenced factors of circulating CTRP6(YCTRP6 = 2.28 + 0.024 XHb A1c+ 0.091 XTG + 0.087 XTNF-?;R2= 0.197,P <0.001).Using a multivariate logistic regression analysis,circulating CTRP6 was related to T2 DM and IGT,even after controlling for anthropometric variables and others,When serum CTRP6 levels were divided into four tertiles in all study subjects(tertile 1,< 286.7 ?g/L;tertile 2,286.8 – 364.1 ?g/L;tertile 3,364.1-476.8 ?g/L;tertile 4,> 476.8 ?g/L for IGT and tertile 1,<312.5 ?g/L;tertile 2,312.5-418.4 ?g/L;tertile 3,418.4-557.7?g/L;tertile 4,>557.7 ?g/L for T2DM),we found that in the tertile 4 of CTRP6 concentration,the odds ratio of developing IGT was 3.20(95% CI 1.48;6.91)(vs.tertile 1,P <0.01),whereas in another tertile 4,the odds ratio of developing T2 DM was 43.85(95% CI 14.61;131.60)(vs.tertile 1,P <0.01).Based on ROC analyses,we found that for IGT subjects,the area under the ROC curves(AUC)was 0.61(P <0.01)with a sensitivity of 60.2 %,specificity of 60 % and for T2 DM patients,AUC was 0.81(P <0.001)with a sensitivity of 64.4 %,specificity of 84.8 %.The best cutoff values of circulating CTRP6 for predicting IGT and T2 DM were 368.8 and 478.2 ?g/L,respectively.Conclusion: As a new adipocytokine,the increase of plasma CTRP6 level is closely related to the occurrence and development of T2 DM.The changes of CTRP6 can well predict the progression of IGT and T2 DM.Therefore,CTRP6 can be used as a new clinical test to predict and assess the development of type 2 diabetes and insulin resistance.PART ? EFFECTS OF DIFFERENT INTERVENTIONS ON PLASMA CTRP6 LEVELSObjectives: To analyze the effect of hyperglycemia and/or hyperinsulinemia on plasma CTRP6,TNF-? and adiponectin levels in healthy people.Methods: After a 12-hour overnight fast,a 75 g OGTT was performed on healthy subjects.Blood samples were drawn at indicated time points for the measurements of blood glucose and serum insulin.Serum CTRP6,adipoq and TNF? levels were also measured at indicated time point in 48 healthy individuals(24 man and 24 women).The levels of CTRP6,TNF-? and adiponectin were detected by ELISA as mentioned above.Results: After oral glucose challenge,circulating CTRP6 levels exhibited a similar change with blood glucose and insulin.CTRP6 concentrations increased to an apogee at 30 min and then progressively decreased until 60 min,finally returned to the baseline at 120 min(from 379.2 ± 148.4 ?g/L at 0 min to 571.4 ± 176.8 ?g/L at 30 min and then to 436.4 ± 163.2 ?g/L at 60 min,and finally to 398.3 ± 160.7 at 120min;vs.baseline P <0.05 or P <0.01).Similarly,Adiponectin concentrations in healthy individuals were increased rapidly at the early phase of OGTT and then decreased gradually at the late phase(from 18.3 ± 7.9 ?g/L at 0 min to 29.1 ± 12.1 ?g/L at 30 min,and then to 21.3 ± 10.0 ?g/L at 60 min,and finally to 19.5 ± 8.6 ?g/L at 120min;vs.baseline P <0.05 or P <0.01).Furthermore,the trend of TNF? levels is also similar to that of CTRP6 and Adiponectin levels during the OGTT,which reached its peak at 30 min and then reduced until 120 min(from 1.67 ± 0.76ng/L at 0 min to 3.15 ± 1.25 ng/L at 30 min,and then to 2.43 ± 1.19 ng/L at 60 min,and finally 1.89 ± 0.96 ng/L at 120min;vs.baseline P <0.05 or P <0.01).Conclusions:The dynamic changes of CTRP6 during the OGTT may be associated with insulin and glucose levels in vivo and indicate that CTRP6 may be a metabolic and nutritive regulator.