Investigation Of Associations Of Cystatin C With Insulin Resistance And β Cell Function In Patients With Type 2 Diabetes Mellitus

Background:Nowadays, as the development of social economy, the epidemic effects of diabetes mellitus has been developing rapidly throughout the world with the progress in quality and environment of the people’s life. By now diabetes mellitus has been on its road to the third most threatening metabolic disease for the health of human being, following malignant carcinoma and cardiovascular diseases. Type 2 diabetes mellitus, a clinic syndrome caused by genetic and environment factors and characterized as disturbance of carbohydrate metabolism, of which the pathophysiologic mechanisms are decreases in pancreatic islet functions and insulin, accounts for more than 90% of the population diagnosed as diabetes mellitus. Cysteine protease inhibitor C, or Cys-C for short, produced by virtually all nucleated cells, participates in regulations of proteolysis of several proteins. Recent evidence from researches on Cys-C suggested that Cys-C can be used in the prediction of diabetes mellitus, and it is strongly coupled with microvascular complications of diabetes mellitus. However, few researches mentioned the relationship between Cys-C and pancreatic islet functions or insulin-resistance.Objective:In our study, pancreatic functions of baseline, early phase and all phases are represented by area under the curve of corresponding C-peptide release, measuring insulin-resistance with Homa-IR and insulin sensitivity with Homa-S. The study aims at identifying whether there are relationships between Cys-C and pancreatic islet function or insulin-resistance.Methods:We selected cases of type 2 diabetes mellitus admitted by Shandong University Qilu Hospital during the date from 2012.06.31 to 2015.03.31, among whom there are 117 male patients and 112 female patients, with the average age of 58.74±10.30 years old, ranking from 26 to 85. All of them volunteered as subjects and received our surveys on general information, physical examination and laboratory tests. The general information includes basic information, past medical history, family history, medicine taken. The information of physical examination includes height, weight and waistline. The information of laboratory tests are gathered from venous blood sample get after fasting for 8h or 10h after taking inslin, including total cholesterol(TC), glycerin trilaurate(TG), low density lipoprotein(LDL), high density lipoprotein(HDL), fasting plasma glucose(FPG), fasting insulin(FINS), glycosylated hemoglobin(HbAIC), cysteine protease inhibitor C(Cys-C), serum creatinine(Cr), free fatty acids(FFA), etc. Then plasma glucose, insulin and C-peptide are tested 0.5h, 1h,2h and 3h separately after taking 75 g of glucose through venous blood sample. The data entry is accomplished with Microsoft Office Excel 2010, the calculation of the area under the C-peptide release curve is accomplished with Graph Pad Prism5. All of the analyses are accomplished with SPSS 16.0.Results:1. The compare among different levels of serum Cys-C of patients suffering from type 2 diabetes mellitus indicates that ages, course of disease, BMI, SBP, serum creatinine, morbidity rate of heart disease and complications of diabetes mellitus, level of Homa2%B or AUC2h would increase while the level of CCR and Homa2%S would decrease with the increase of Cys-C. As for HomaIR and AUC0.5h, the level would increase with the increase of Cys-C when the level of the latter is limited in normal ranges, but would decrease slightly in the group with abnormal level of Cys-C2. Abnormal level of Cys-C is an independent risk factor of diabetic nephropathy, diabetic retinopathy and diabetic neuropathy according to the results of logistic regression analysis.3. Positive linear correlation between Cys-C level in serum and the level of Homa2 IR or area under curve for C-peptide of 0.5h, after correction of ages, gender, BMI, course of disease, blood fats, history of taking alcohol beverage or smoking, leukocyte count, history of angiocardiopathy or Cr.4. Relatively higher level of serum Cys-C within reference ranges or abnormally higher level of Cys-C are both independent risk factors of insulin-resistance for patients suffering from type 2 diabetes mellitus according to the results of logistic regression analysis, of which the risk would increase with the increase of Cys-C.5. The level of Cys-C is not an independent risk factor of pancreatic islet dysfunction for patients suffering from type 2 diabetes mellitus according to the results of logistic regression analysis.Conclusion:1. Various complications of diabetes mellitus increase with the increase of Cys-C level.2. Higher level of serum Cys-C is an independent risk factor of insulin-resistance for patients of type 2 diabetes mellitus.3. The level of serum Cys-C is not related with pancreatic islet functions of patients suffering from type 2 diabetes mellitus.