The Factors Influencing Plasma Homocysteine In Type 2 Diabetes And The Relationship Between Homocysteine And Diabetic Vascular Disease

Diabetic angiopathy is a major cause for the mortality and morbidity of diabetes mellitus(DM). Apart from diabetes-related risk factors (hyperglycemia, hyperinsulinemia , obesity, hypertension, hypertriglyceride -mia), traditional risk factors (hypercholesterolemia, smoking) are known to increase the risk of vascular disease in patients with diabetes. However, the atherothrombotic process in diabetes is complex and alternative risk factors, such as hyperhomocysteinemia, may be involved. Elevated plasma homocysteine levels have been linked to the development of both arterial and venous vascular disease. It is also suggested that homocysteine may play an important role in the development of macro- and microvascular complications of diabetes. But the factors influencing the plasma homocysteine in diabetes, the relationship between total plasma homocysteine and the diabetic angiopathy and if homocysteine-lowering treatment can be helpful for the progression of diabetic nephropathy are all still uncertain. So this study was performed based above aspects.The survey of the relationship between plasma total homocysteine and type 2 diabetes and its vascular complications[Objective] To survey the factors influencing the plasma tHcy in type 2 diabetes, study the relationship between the tHcy and type 2 diabetic vascular complications and then to explore the possible mechanism.[Methods] A total 339 patients with type 2 diabetes were screened in our out- and inpatient clinic within 1 year. Fasting blood samples were collected for measuring FBS,insulin,HbAlc,CRP,fibrinogen,tHcy, and postprandialblood were collected to test the PBS and insulin. Plasma tHcy was measured by HPLC with reverse phase separation and fluorescence detection. Overnight timed urine sample were used for measuring the urine Alb/Cr. [Results] The incidence of each complication was 175 (51.6%) of macrovascular disease, 169( 49.9% )for DN, 206(60.8%) for DR in this study population,respectively. Mean level of tHcy was 15.1±11.5umol/L(median: 12.4 umol/L),and the incidence of HHcy was 32.7% ( 111/339 ), and most were mild hyperhomocysteinemia ( 94.1% ) . Using multivariate regression, plasma tHcy was independently correlated to BMI, diabetic duration, HbAlc, fibrinogen, CRP, urine Alb/Cr and ISI. And tHcy also was an independent predictor of diabetic macrovascular disease (OR=0.7328, P<0.05), DN (R=0.5851,p=0.001) and DR(OR=0.6407,p=0.001). Logistic regression analysis showed that CRP and fibrinogen were also independently related with the occurrence of diabetic macrovascular disease (OR= 0.179,P<0.05; OR=0.8364,P<0.05,respectively ) , DN ( OR=0.0297,p=0.001; OR=0.8173, p=0.001,respectively) and DR ( OR=0.1128,p=0.001; OR=0.8379,p=0.001, respectively) . [Conclusions] In type 2 diabetes, tHcy was affected by BMI,duration of diabetes .metabolic control and insulin sensitivity index; And tHcy could be regarded as a major risk factor of type 2 diabetic macro-and microvascular complications.The impact of intensive insulin therapy on the plasma total homocysteine and diabetic renal disease in type 2 diabetes[Objective] To study the impact of simple insulin intensive therapy on the plasma tHcy and the renal disease in type 2 diabetes. [Methods] A total 68 patients with type 2 diabetes were recruited .At baseline and the end of 3 month therapy, fasting blood sample were collected for measuring FBS* HbAlc> CRP, tHcy and other routine biochemistry testing, and postprandial blood were collected to measure PBS . Overnight timed urine sample wereused for measuring the urine albumin, urine Cr, urine TGF-pl and the activity of urine NAG. [ Results ] FBS.PBS and HbAlc decreased significantly (p<0.01) after 3 month intensive insulin therapy ,and tHcy also decreased, but it did not reach the statistic significance (p>0.05). 7.0 % of HbAlc was selected as the cut point judging the level of metabolism control. The HbAlc level was less than 7.0% in 31 (45.6%) patients after insulin treatment alone. In these patients, FBS.PBS and HbAlc significantly decreased ,as well as the plasma tHcy, urine Alb/Cr, urine TGF-|31,when compared with that of pre-treatment. Multiple linear regression analysis showed the change of plasma tHcy was independently related to the change of CRP (r=0.191,p=0.044) ,urineTGF-pi (r=O.538,p=O.OOl) ,and urine NAG activity (r=0.193,p=0.013). Otherwise, the change of urine Alb/Cr(r=0.591,p=0.001) ,urine TGF-pl (r=0.632,p=0.001) and urine NAG activity (r=0.519,p=0.001 ) were all related to the change of plasma tHcy independently! Conclusions jlnsulin therapy might decrease the plasma tHcy level by improving the metabolic control, and then it might contribute to delaying the progression of diabetic renal disease.The impact of insulin resistance induced by high-fat diet on the plasma homocysteine of the rats[Objective] To study the effect of pioglitazone on the plasma homocysteine in insulin resistance rats induced by high-fat diet. [Methods] 24 Wistar rats were randomized into 3 groups : control group (n=8) was fed with normal diet, high-fat food was given to high-fat group and pioglitazone group, and pioglitazone (lOmg/kg) was administered by gavage daily for 11 weeks to pioglitazone group. At week 11, glucose tolerance test was performed, and serum insulin, fasting glucose and plasma homocysteine were detected. Viscus adipose was weighted and then calculated the ratio of viscus adipose over the body weight. [Results] Fasting glucose, fasting insulin.insulin resistance index (IRI), and the viscus adipose were significantly different among 3 groups. Fasting glucose, fasting insulin, IRI, and the viscus adipose were all significantly lower in pioglitazone group than that in high fat group(p<0.01). And the plasma homocysteine was significantly decreased in pioglitazone-treated rats (8.8±1.39umol/L) compared with other two groups(control group:9.95±2.40umol/L and high fat group: 35.7±14.1umol/L). Correlation analysis showed that all fasting glucose, fasting insulin, IRI, and the viscus adipose were the factors influencing the plasma homocysteine level. Stepwise regression test showed only fasting glucose ( r = 0.504 , p = 0.031 ) and IRI ( r = 0.302, p = 0.046 ) independently affected the level of plasma homocysteine. [ Conclusion I It is concluded that insulin resistance was asscioated with elevated tHcy,while pioglitazone could lower plasma homocysteine in insulin resistance Wistar rats induced by high-fat diet.The effect of cyanocobalamin and methylcobalamin (methyI-B12) on the renal disease of type 2 diabetic Kkay mice with hyperhomocysteinemia[ Objective 1 To observe and compare the effect of cyanocobalamin and methylcobalamin (methyl-B12) on the renal disease of type 2 diabetic Kkay mice with hyperhomocysteimia induced by high methione food. [ Methods ] The type 2 diabetic Kkay mice were fed with 3% methionine high fat diet,until the level of serum homocysteine increased to 15umol/L. Then the mice were randomized into 3 groups xontrol group, cyanocobalamin and methylcobalamin groups respectively. The serum homocysteine were measured at 0,1,2,4,8 week, and 24 hour urine were collected for detecting the urine albumin and creatinine. [Results] The level of homocysteine was progressively increased in control group, and decreased after cyanocobalamin and methylcobalamin administration. The UAE and urine NAG activity of all groups were increased without use of hypoglycemic...