Insulin Resistance And Lipid Metabolic Disorder In Peritoneal Dialysis Patients: Prognosis And Therapy

Insulin Resistance and Lipid Metabolic Disorder in Peritoneal Dialysis Patients:Prognosis and TherapyPart IInsulin Resistance as a Predictor of Cardiocerebrovascular Morbidity and All Cause Mortality in Peritoneal Dialysis Patients: A Prospective Cohort StudyBackgroundInsulin resistance (IR) contributes to metabolic disorder. The overload of glucose aggravates IR in PD patients. Whereas IR, metabolic disorder, obesity are the established risk factors for increased morbidity and mortality in the general population, epidemiological studies and clinical trials in end stage renal disease patients have created uncertainties with regards to the impact of metabolic disorder on mortality. Prospective study about the relationship between IR, metabolic disorder and cardiocerebrovascular morbidity and mortality in nondiabetic PD patients is limited. We hypothesized that high level of insulin resistance is associated with dysmetabolism development and cardiocerebrovascular morbidity and mortality in nondiabetic PD patients.MethodsA cohort of 69 nondiabetic uremic patients was prospectively enrolled. They had been treated by regular peritoneal dialysis for more than 3 months. At baseline, the HOMA-IR (fasting serum insulinμU/mL×fasting serum glucose mmol/L/22.5) formula was used to determine the insul in resistance. The cut-off point for IR was established by the median. According to it, the patients were divided into two groups:High IR group (IR-H group) if HOMA-IR was greater than or equal to the median and low IR group(IR-L group) if less than this level. The differences of dysmetabolism parameters (BMI, serum cholesterol, triglyceride, HDL, LDL, CRP, total adiponectin, leptin, resistin) and development of new onset diabetes mellitus, cardiocerebrovascular morbidity and all-cause mortality were investigated between the two groups.ResultsAt the beginning of the study, average age was 61.95±16.06years, 37 were female, and the median time on PD was 15.17months. The average follow-up period was 22.82±11.07 months. The cut-off point of IR was 2.86: IR-H group, HOMA-IR(?)2.86(n=35);IR-L group, HOMA-IR<2.86 (n=34). Average age, PD duration,24 hour peritoneal dialysate glucose absorption, average blood pressure, the distribution of primary renal disease and residue renal function did not differ between the two groups. The level of BMI, average fasting serum glucose, average ferritin, median triglyceride, median CRP, median leptin were statistically significantly higher in IR-H group than those in IR-L group. However, median HDL, median adiponectin levels were statistically significantly lower in IR-H group than those in IR-L group. There were positive correlations between HOMA-IR and CRP, leptin, triglycerides. Inverse associations were observed between HOMA-IR and HDL, HOMA-IR and adiponectin.There were 10 patients in IR-H group but no patient in IR-L group developed diabetes mellitus (P=0.001). During the follow-up period,11 Cardiocerebrovascular events (including cerebral infarction 4, cerebral hemorrhage 2, myocardial infarction 1, left heart failure 2, pulmonary infarction 1, and phlebothrombosis in lower limb 1) were occurred in IR-H group but only 1 event (angina pectoris) occurred in IR-L group. HOMA-IR were found to be significant predictors of cardiocerebrovascular events even after adjusted for age and gender (RR=16.35; 95%CI:4.75-56.29; P=0.O11). There were 9 patients died (cardiocerebrovascular events 5, cancer 1, serious peritonitisl, unknown reason 2) in IR-H group but only 2 patients died (serious pneumonia 1, intestinal perforationl) in IR-L group. The survival curves estimated by the Kaplan-Meier method and log rank test showed that patients in IR-H group had a significantly lower survival rate compared with those in IR-L group (x2=4.76, P=0.0291) HOMA-IR remained to be significant predictors of all cause mortality even after adjusted for age, gender, residue renal function, serum albumin (RR=3.28;95%CI:1.32-8.16;P=0.O11). The percentage of patients who died because of cardiocerebrovascular disease in IR-H group were higher than that in IR-L group (IR-H group:5/35, IR-L:0/34; P=0.029)ConclusionsInsulin resistance is particularly prevalent in PD patients. PD patients who had higher IR level had more serious metabolic disorders, higher rates of diabetes development, cardiocerebrovascular morbidity and all cause mortality. It was accepted that being able to correct the insulin resistance could be a novel therapeutic approach to reduce mortality in this cohort. PartⅡTwelve weeks of pioglitazone therapy significantly attenuates dysmetabolism and reduces inflammation in prevalent peritoneal dialysis patients:A randomized, cross-over trialBackgroundsIn the first part, we have demonstrated that cardiocerebrovascular disease is the major cause of mortality in PD patients, which is attributable to a higher prevalence of insulin resistance and metabolic disturbance. However, treatment for metabolic disorder, esp. hypertriglyceride is difficult in PD patients in China where the icodextrin dialysate has still been unavailable. The aim of this study is to investigate the effect of oral pioglitazone on lipid metabolism, insulin resistance, inflammation and adipokine metabolism in PD patients.MethodsWe randomly assigned 36 prevalent PD patients with serum triglyceride levels> 1.8mmol/L to receive either oral pioglitazone (15mg once daily) or no medication for 12 weeks. After a four weeks wash out, patients then continued with the alternative therapy. Anthropometrics and fasting serum triglycerides, low density lipoprotein(LDL), high density lipoprotein(HDL), glucose, insulin (for calculation of HOMA-IR), C-reactive protein(CRP), liver function tests, leptin, total adiponectin and resistin were measured every six weeks.ResultsAll 36 patients (10 diabetes,26 non-diabetes) completed the study. Although no significant differences of 12 weeks therapy of pioglitazone on serum TG and LDL were recorded, pioglitazone significantly increased HDL level (0.94±0.20 to.1.00±0.21mmol/L, p=0.0038). HOMA-IR level (6.23(1.39-29.03) to 5.28(0.97-14.95), p=0.0060) and fasting serum glucose level (7±2.35 to 6.6±2.45mmol/L, p=0.0106) were decreased significantly, whereas no significant change was occurred in HbAlc level. Pioglitazone significantly reduced median CRP level from 11.30(0.18-53) to 3.36 (0.17-26.30) mg/L (p=0.0049). Total adiponectin level (13.38±8.86 to.49.87±33.34, p<0.0001) increased and resistin level decreased (33.09±16.81 to.28.89±10.76, p=0.0219) significantly. There were also no significant changes in BMI after treatment. Pioglitazone was well tolerated that no adverse effects as hypoglycemia, hepatic impairment and heart failure were observed during the study period except that 1 patient with significant residue renal function developed lowered-extremity edema.Conclusion12 weeks of pioglitazone (15mg once daily) did not alter serum triglycerides in prevalent PD patients, but decreased insulin resistance, inflammation and attenuated adipokine imbalance. Pioglitazone may be a beneficial therapy for this patient group.