Total plasma homocysteine is associated with hypertension in Type I diabetic patients.
OBJECTIVE
Although hyperhomocysteinaemia and methylenetetrahydrofolate reductase gene polymorphism are accepted risk factors for cardiovascular disease, their association with micro angiopathy or blood pressure in diabetic patients is still being debated. This study explores the relation between plasma homocysteine concentrations, methylenetetrahydrofolate reductase gene polymorphism, hypertension, diabetic microvascular and macrovascular complications associated with kidney function.


METHODS
Vascular complications, hypertension, methylenetetrahydrofolate reductase genotype (RFLP with Hinf I digestion), and total plasma homocysteine (HPLC) were investigated in 389 well-characterized Type I (insulin-dependent) diabetic patients with normal (GFR> or=75 ml x min(-1) x (1.73 m(2))(-1); n=273), or impaired renal function (GFR <75 ml x min(-1) x (1.73 m(2))(-1); n=116).


RESULTS
Patients with microvascular and macrovascular complications showed higher total plasma homocysteine concentrations than those without complications. However, after the data for GFR (main determinant for plasma homocysteine) was adjusted we observed that plasma homocysteine concentrations greater than 8.6 micro mol/l in patients with normal GFR are not related to vascular complications, but to hypertension (8.6-11.3 micro mol/l: OR 1.9; >11.3 micro mol/l: OR 3.7). The risk for coronary heart disease (CHD) was also enhanced by a plasma homocysteine concentration greater than 11.3 micro mol/l (OR 5.9). Although the T allele was an independent determinant of plasma homocysteine, the methylenetetrahydrofolate reductase gene polymorphism was neither associated with diabetic vascular complications nor with hypertension.


CONCLUSIONS
Increased plasma homocysteine concentrations but not the T allele per se, enhance the risk of hypertension and of CHD in Danish Type I diabetic patients with normal renal function.
Neugebauer
S
S
Third Department of Internal Medicine, Fukushima Medical University, Hikarigaoka 1, 960-1295 Fukushima, Japan. sneugeba@fmu.ac.jp
Tarnow
L
L
Stehouwer
C
C
Teerlink
T
T
Baba
T
T
Watanabe
T
T
Parving
H-H
HH
D000328:Adult; D000419:Albuminuria / Q000453:epidemiology / Q000235:genetics; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics; D003925:Diabetic Angiopathies / Q000453:epidemiology* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)