The Relationship Between Insulin Resistance And The Urinary Albumin Creatinine Excretion Ratio In Metabolic Syndrome Patients

BACKGROUND: The metabolic syndrome(Met S)is a cluster of risk factors,which occur together more frequently than by chance alone and subsequently lead to cardiovascular,chronic kidney diseases and type 2 diabetes mellitus.The risk factors are high blood pressure,dyslipidemic profile,high fasting glucose levels and central obesity.The primary pathophysiological defect in metabolic syndrome is the development of insulin resistance.The involvement of the metabolic syndrome with chronic kidney disease is a recent finding and many studies have been carried out to confirm this hypothesis.There have been many previous studies involving the insulin resistance syndrome and the development of albuminuria in diabetes type 1 and diabetes type 2 patients.As far as we know,our study is a novel one involving the metabolic syndrome as the study sample.The aim of our study was to examine the cross-sectional and longitudinal relationship between insulin resistance(IR)and the worsening of urinary albumin to creatinine excretion ratio(UACR)and the various factors that contributed to this relationship in Chinese patients with the metabolic syndrome.RESEARCH DESIGNS AND METHODS: Our sample was derived from 10,207 people from the REACTION Study,which was launched by the Chinese Medical Association.The data was collected from August 16 th,2011 to December 10 th,2011.All the participants were from Dalian City of Liaoning province,China and above 40 years of age.3429 participants were selected as the sample,according to National Cholesterol Education Program Adult Treatment Panel III(NCEP-ATP III)criteria with modification on waist circumference cutoff for Asian population suggested by the 1998 World Health Organization Asian Pacific Guideline,for the diagnosis of metabolic syndrome.For the prospective study,our sample consisted of metabolic syndrome patients having UACR < 30 mg/g,missing data were removed,and the total sample consisted of 3003 patients out of which only 1594 participated in a follow-up examination after three years.A standardized questionnaire was used to collect personal data from the subjects.Anthropometric measurements,comprising of body height,body weight,and waist and hip circumferences were determined.Body mass index(BMI)was calculated.The blood pressure-systolic blood pressure(SBP)and diastolic blood pressure(DBP)and heart rate of each individual were determined.From each participant,blood samples were drawn to be analyzed.Lipid panel(total cholesterol,triglycerides-TG,high-density lipoproteins-HDL cholesterol and low-density lipoprotein-LDL cholesterol)was assayed.Fasting plasma glucose levels(FPG),fasting insulin levels(FINS),glycosylated hemoglobin(Hb A1c),postprandial glucose levels(PPG)and liver function tests(alanine transferase-ALT,aspartate transferase-AST and gamma glutamyl transferase-GGT)were measured.At the baseline,insulin resistance was assessed by the index of homeostasis model assessment of insulin resistance(HOMA-IR)method.The HOMA-IR was calculated according to the formula: HOMA-IR was divided into four quartiles for the cross-sectional(Q1-Q4)and four quartiles for the prospective study(G1-G4)respectively.The UACR was determined both at baseline and follow-up.The creatinine concentration in urine and the urinary albumin concentration were measured in a random morning sample.UACR was calculated according to the formula: UACR was expressed in mg/g.For our study,we defined microalbuminuria simply as the UACR of 30 to 299 mg/g.RESULTS: I.Cross-sectional study 1.According to the cross-sectional studies,there was a significant increase in the UACR with gradual increase in the HOMA-IR quartiles(p < 0.005).The highest increase in UACR was with the 4th quartile of HOMA-IR.2.The possible risk factors demonstrating a gradual increase with increasing HOMA-IR quartiles included: BMI(p < 0.000),waist circumference(p < 0.000),LDL(p < 0.01),total cholesterol(p < 0.01),TG(p < 0.00)and the overall glucose profile-FBS(p < 0.00),PPG(p < 0.00),Hb A1c(p < 0.00),FINS(p < 0.00).HDL(p < 0.00)showed a decrease with the rising HOMA-IR quartiles.3.Pearson correlation studies showed a positive correlation between UACR and HOMA-IR(r = 0.181;p = 0.000),age(r = 0.049;p = 0.004),SBP(r = 0.215;p = 0.000),DBP(r = 0.099;p = 0.000),heart rate(r = 0.067;p = 0.000),BMI(r = 0.084;p = 0.000),waist circumference(r = 0.095;p = 0.000),total cholesterol(r = 0.042;p = 0.014),GGT(r = 0.036;p = 0.037),FBG(r = 0.224;p = 0.000),PPG(r = 0.210;p = 0.000),Hb A1c(r = 0.229;p = 0.000)and FINS(r = 0.074,p = 0.000).4.Multiple stepwise regression analysis showed that HOMA – IR is a risk factor for the rise in UACR(β = 0.046;p < 0.008),independently of gender(β = 0.058;p < 0.001),SBP(β = 0.179;p < 0.000),waist circumference(β = 0.051;p < 0.024),GGT(β = 0.037;p < 0.031),PPG(β = 0.060;p < 0.029)and Hb A1c(β = 0.156;p < 0.000).II.Prospective study 1.In the prospective study,within each quartile of HOMA-IR,there was a stepwise increase in the levels of UACR.The morbidity rate for the UACR and the HOMA-IR were G1-15%,G2-17.1%,G3-20.8%,and G4-31.9% respectively.2.Cox proportional hazards models were used to estimate the hazards ratio(HR)associated with an increase in HOMA-IR.After adjusting for possible confounders,Cox proportional hazard analysis revealed that insulin resistance was an independent predictor of increase in UACR(HR = 1.023;95% C.I = 1.004-1.043;p = 0.016)and hence renal insufficiency.Also age(HR = 1.027;95% C.I = 1.012-1.041;p = 0.000),SBP(HR = 1.011;95% C.I = 1.005-1.017;p = 0.000),BMI(HR = 1.056;95% C.I = 1.023-1.089;p = 0.001),TG(HR = 1.088;95% C.I = 1.012-1.170;p = 0.023)stand out as independent predictors of increase in UACR.CONCLUSIONS: 1.According to our cross-sectional study,in a Chinese population of metabolic syndrome patients,insulin resistance is an independent risk factor for the increase in urinary albumin to creatinine ratio.Higher the insulin resistance,the higher the level of urinary albumin – creatinine ratio.2.According to our prospective study,insulin resistance is a predictor of the rise in urinary albumin to creatinine ratio,irrespective of adjustments in the biochemical parameters.Also age,systolic blood pressure,body mass index and triglycerides emerged out to be independent predictors of the development of albuminuria.