Features And Significance Of Serum ADMA Level In Type2Diabetic Coronary Heart Disease With Hypothyroidism

Objective: As an important marker gene of endothelial dysfunction, highlevels of asymmetric dimethylarginine (ADMA) are correlated with impairedendothelial function and thus promote atherosclerosis. There are growingevidences showing that ADMA levels are increased with type2diabetesmellitus, coronary heart disease, hypothyroidism, hypercholesterolemia, highlevels of homocysteine, the intima-media thickness of the carotid artery andhypertension. This study detects the serum concentration of ADMA, the highsensitive C-reactive protein (hsCRP), the fasting glucose, the insulin, theblood-fat, etc.To explore the association between hypothyroidism and type2diabetes mellitus with coronary heart disease through determining the level ofADMA. The significance of the study is to get more evidences for theetiopathogenisis, pathogenesis, iatreusis and therapeutic effect of diabeticcardiopathy, and may also provide this marker gene for clinical application.Methods: The study adopted case-control study method, randomlyselected118cases of healthy controls and type2diabetes with or withoutcoronary heart disease in the Department of Endocrinology and MedicalExamination Center of The Second Hospital of Hebei Medical University. Allthe cases were without cerebrovascular disease, diabetic retinopathy, diabeticnephropathy or diabetic neuropathy. They were divided into4groups: healthycontrols(G1),30cases; simple type2diabetes(G2),27cases; type2diabeteswith coronary heart disease(euthyroidism; G3),34cases; type2diabetes withcoronary heart disease(hypothyroidism; G4),27cases. Asymmetricdimethylarginine (ADMA) was determined by enzyme linked immunosorbentassay(ELISA), CRP by the immunoturbidimetric, and insulin bychemoluminescence assay. Meanwhile, the clinical and blood biochemicalindices were also detected. All the data were processed with statistical software packages SPSS13.0.Results: The average ages of G3and G4were respectively older than G1and G2(P<0.01), G4was older than G3(P<0.05), but there was no significantdifference between G1and G2in age (P>0.05). The courses of type2diabetesin G3and G4were longer than G2(P<0.001), while it was not differentbetween that of G3and G4(P>0.05). BMI between groups were not different(P>0.05). By Chi-square test, the sex between groups were not different(P>0.05).The concentrations of serum thyrotropic-stimulating hormone (TSH) inG4were significantly higher than that in the three groups(G1,G2,G3),however,the difference in that groups(G1,G2,G3)may not exist(P>0.05). Theconcentrations of serum free triiodothyronine(FT3) in G3and G4were lowerthan that in G1and G2(P<0.001),the difference not only between G3and G4but also between G1and G2may not exist(P>0.05). The statisticalsignificance between groups of serum free thyroxine may not exist(P>0.05).The concentrations of serum triglyceride(TG) in clinical case-controlgroups(G2,G3,G4) were significantly higher than that in healthy-controlgroup(G1)(P<0.01), the difference in that groups(G2,G3,G4)may notexist(P>0.05). The concentrations of serum high density lipoprotein(HDL) inclinical case-control groups(G2,G3,G4) were significantly lower than that inhealthy-control group(G1)(P<0.001), the difference in thatgroups(G2,G3,G4)may not exist(P>0.05). The statistical significance betweengroups of serum cholesterol(CHOL) and low density lipoprotein(LDL) maynot exist(P>0.05).The concentrations of serum high sensitive C-reactive protein (hsCRP)inclinical case-control groups(G2,G3,G4) were significantly higher than that inhealthy-control group(G1)(P<0.05), this concentrations in G3were higherthan in G2(P<0.05),however, the difference not only between G4and G2butalso between G4and G3may not exist(P>0.05). The insulin resistanceindex(HOMA-IR) in G2was significantly higher than thegroups(G1,G3,G4)(P<0.05),but the difference in that groups(G1,G3,G4)may not exist(P>0.05).The concentrations of serum asymmetric dimethylarginine (ADMA) inclinical case-control groups(G2,G3,G4) were significantly higher than that inhealthy-control group(G1), moreover, type2diabetes with coronary heartdisease(euthyroidism;G3) higher than Simple type2diabetes(G2), type2diabetes with coronary heart disease(hypothyroidism;G4) higher than G3. ByRank-sum test, the differences between each groups exist(P<0.05).Thedifference among the four groups still exists as removaled the factor of age.By analyzing the subset of clinical case-control groups(G2,G3,G4)according to the samples with or without artherosclerosis of the carotid artery,hypertension and fatty liver. Samples with artherosclerosis of the carotid arteryhad significantly higher levels of ADMA compared to the samples withoutartherosclerosis of the carotid artery. Those with hypertension had higherlevels of ADMA compared to those without hypertension. However, thedifference between with fatty liver and without may not exist (P>0.05).By Spearman Correlate Tests, the levels of serum ADMA were positivelycorrelated with age, triglyeride, fasting blood glucose, C-reactive protein,thyrotropic-stimulating hormone and glycosylated hemoglobin （r=0.489,P<0.001；r=0.348, P<0.001；r=0.463, P<0.001；r=0.302, P<0.01；r=0.428,P<0.001；r=0.498, P<0.001）, and negatively correlated with high densitylipoprotein(r=-0.353, P<0.001).By Binary Logistic Regression, artherosclerosis of the carotid artery, thelevels of ADMA,glycosylated hemoglobin, course of type2diabetes and agewere the risk markers of the people in type2diabetes with coronary heartdisease (OR:19.898,4.813,2.281,3.985,8.108), and the protect marker wasthe high level of FT3(OR=0.013).By Multiple Stepwise Regression, age, artherosclerosis of the carotidartery, TSH and HDL were the risk markers of the levels of ADMA in patientswith type2diabetes(regression coefficient:0.176，2.741，0.167，-3.529;R=0.612; R2=0.374). Conclusion:1This study discovered that the levels of ADMA in the patients with type2diabetes were higher than healthy people. Among the type2diabetespatients, patients with coronary heart disease were higher than those withoutcoronary heart disease. The highest levels of ADMA was discovered in thetype2diabetes patients not only with coronary heart disease but also withhypothyroidism.2People with hypertension or artherosclerosis of the carotid artery hadthe higher level of ADMA, which may play an important role in pathogenesisof hypertension or artherosclerosis.3The level of serum ADMA was positively correlated with age, TG, FBG,CRP, TSH and HbA1c, and negatively correlated with HDL.4The elevated level of serum ADMA was tightly related to people withtype2diabetes and coronary heart disease，and became the independent-riskmarker of type2diabetes with coronary heart disease.5The level of serum ADMA in type2diabetes with coronary heartdisease and hypothyroidism was significantly higher than those withouthypothyroidism. Through the elevated level of serum ADMA, the patients0ftype2diabetes with hypothyroidism may increase the risk of coronary heartdisease.