The Relationship Between Rhoa Andtype2Diabeties Mellitus And Its Angiopathy

Objective: Type2diabetes mellitus (T2DM) comprises a group ofcommon metabolic disorders due to insulin deficiency and resistance. Itdevelops as a result of synergistic effects of genetic and environmental factors.Its characteristic is chronic hyperglycemia. As the disease progresses, variouscomplications of T2DM will occur and develop. Its angiopathy is the maincause of physical disability and death for diabetes patiens. T2DM angiopathyconsists of macroangiopathy and microangiopathy. Macroangiopathy mainlyshows atherosclerosis of cardiovascular, cranial vessel and lower limbs vessel.Microangiopathy mainly shows diabetic nephropathy and diabetic retinopathy.In recent years, the study of RhoA/ROCK signal transduction pathway anddiabetes has been foused by many scholars. RhoA is one important memberof the small GTPase Rho family. It plays a molecular switch role in cells.Actived RhoA enables target molecule in downstream—Rho-associatedkinases (ROCK), to regulate lots of basic life activities and pathologicalphysiology process in cells. A lot of studies indicated the signal would betransduced to the cell by the small GTPase when the vascular wall cellreceived the harmful stimulate. The small GTPase would activate itsdownstream target protein (Rho-associated kinases) and induce the changes inthe fuction, form, phenotype and gene expression of vascular endothelial celland vascular smooth muscle cell, which participated in the process of T2DMand T2DM angiopathy. But at home and abroad the studay of RhoA serumlevel for people with diabetes has been studied little. The RhoA level inNon-patient population, Diabetes patients without complications and Diabetespatients with vascular complications were detected in order to discuss theassociation beween RhoA and diabetes mellitus.Methods: According to the standars of diabetic diagnosis and typing put forward by WHO in1999, a total of120patients with type2diabetes wererecruited. The patients were further divided into three groups:40cases withoutdiabetic complication,40cases with microangiopathy and40cases withmacroangiopathy respectively.40healthful individuals who had carried onphysical examination in our hospital at the same time were taken as normalcontrols. After fasting12hours overnight,5ml blood sample were collectedfrom the elbow vein and separated routinely. Serum was stored at-80℃.1The detection for serum RhoA level: The Enzyme-linkedImmunosorbent Assay method was employed.2Index of the Clinical and biochemical:①Blood glucose, lipids,hepatic and kidney function were measured by all automatic biochemistryanalyzer.②HbA1c and urine A/Cr were detemined by DCA2000~+.③Bloodinsulin was measured by radioimmunoassay, and ISI:-ln(FINS×FPG) andHOMA-IR: ln(FINS×FPG/22.5) were calculated.④Height, body weight weremeasured, and body mass index (BMI) was calculated.3Statistical methods: The data were analyzed by statistical softwareSPSS13.0version. Each group data was inspected whether or not conform tothe normal distribution and homogeneity of variance. Measurement data werepresented by mean±standard deviation(χ±s). Measurement data whichdistributed abnormally, were presented by median (percentiles). TG and FINSwhich distributed abnormally, were analyzed after log-transformed. ANOVAwere applied in the comparison between group, and SNK-q inspect wereapplied in the multiple comparison. Pearson or Spearman correlation analysiswas used in the variables of the total patients. Stepwise logistic regressionanalysis was used for analyzing the contributinon of RhoA and other riskfactors for T2DM and its vascular complications.Results:1There was no significant difference by comparing in age, sexconstituent ratio among normal control group, T2DM without complicationsgroup and T2DM with vascular complications group. There was no significantdifference by comparing in progress history between T2DM without complic- ations group and T2DM with vascular complications group.2BMI in T2DM without complications group was significantly higherthan that in control group(P＜0.05). Compared with T2DM patients, thediabetes patients with vascular complications group had much higher BMI(P＜0.05).3FPG, TC, TG, LDL-C in T2DM without complications group wassignificantly higher than those in controls (all P＜0.05). Compared withT2DM patients without complications group, the diabetes patients withvascular complications group had much higher levels of above factors andHbA1c, FINS, HOMA-IR (P＜0.05), but HDL-C and ISI varied adversely.4Serum RhoA level in T2DM patients without complications group was9.91±3.41ng/ml, markedly higher than4.77±1.92ng/ml in normal controls (P＜0.05). RhoA in the T2DM patients with vascular complications group was21.27±7.00ng/ml, significantly higher than that in normal controls and thediabetes patients without complications group (P＜0.05).5Serum RhoA level in T2DM with macroangiopathy was25.16±5.46ng/ml, markedly higher than14.43±3.92ng/ml in T2DM patients withmicroangiopathy group (P＜0.05).6Serum RhoA was in positive correlation with BMI, TC, LDL-C, FPG,HbA1c, FINS and HOMA-IR (P＜0.01), but in negative correlation withHDL-C and ISI (P＜0.01).7Multiple factor Stepwise logistic analysis showed that BMI, RhoA, TC,TG and LDL-C were the risk factors for T2DM.8Multiple factor Stepwise logistic analysis showed that RhoA, HbA1c,TC and LDL-C were the risk factors for T2DM vascular complicationsoccurrence.Conclusions:1Serum RhoA level in T2DM patients rised, moreover it was higher inthose with vascular complications. High serum level of RhoA was theindependent risk factor for the occurrence and development of T2DM andT2DM vascular complications. RhoA may be the risk predictive factor of T2DM vascular complications.2Serum RhoA level in T2DM patients with macroangiopathy wasmarkedly higher than that in T2DM patients with microangiopathy. There maybe mainly two reasons. Firstly, It is much more close that the relationshipbetween the molecular abnormalities expression and activation ofRhoA/ROCK signal pathway and the occurrence and development ofT2DM macroangiopathy than that in T2DM microangiopathy. Secondly,RhoA may mainly be abnormally expressed in blood in T2DM patientswith macroangiopathy while tissues and organs in patients with micr-oangiopathy.