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V Rantalaiho

Publications and source records attributed to V Rantalaiho.

18 recordsLinked to original sources
PubMed2002

Methylenetetrahydrofolate reductase gene polymorphism, hyperhomocysteinemia and occlusive retinal vascular disease in type 2 diabetic and non-diabetic subjects.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism may cause hyperhomocysteinemia, which affects the vascular endothelium and may induce occlusive vascular disease (OVD). Hypertension thickens small-sized arterial walls and attenuates intramural blood flow. Such OVD can be studied in retinal angiograms as a decrease in the arterio-venous ratio (AVR). Diabetes, by altering microvascular structure and function, in many ways modifies this AVR. OBJECTIVE: To assess whether MTHFR gene polymorphism (C677T) by causing hyperhomocysteinemia affects the retinal AVR in type 2 diabetic and non-diabetic subjects. METHODS: Eighty-four recently diagnosed (< 1 year) type 2 diabetic and 115 non-diabetic subjects were included in the study. Retinal fluoresceine angiograms were recorded and the mean AVR was calculated by measuring transverse vessel diameters at 6 locations. The mean AVR was used as a marker of OVD. The MTHFR VV, VA and AA genotypes were determined by PCR and plasma homocysteine by high-pressure liquid chromatography. RESULTS: In the diabetic subjects with the VV, VA and AA genotypes, the plasma homocysteine levels were 16.5 +/- 7, 12.5 +/- 4.6 and 11.3 +/- 4.9 microM, respectively (p = 0.008, ANCOVA). The corresponding values in controls were 14.6 +/- 3.8, 13.7 +/- 5.7 and 11.6 +/- 4.4 (p = 0.08). Correspondingly, in the diabetic subjects, the AVR values were 0.71 +/- 0.07, 0.75 +/- 0.07 and 0.73 +/- 0.1 (p = NS, ANOVA) and in the control subjects they were 0.8 +/- 0.14, 0.81 +/- 0.12 and 0.76 +/- 0.09 (p = NS, ANOVA). Multiple linear regression analysis (best model chi2 = 18.2, R2 = 0.10, p < 0.001) showed that AVR was related to diastolic blood pressure (t = -3.7, p < 0.001) and GFR (t = -2.2, p = 0.03). There was no relation between the AVR and plasma homocysteine levels. CONCLUSION: In the present study of recently diagnosed type 2 diabetic and non-diabetic subjects, MTHFR gene polymorphism (C677T mutation) slightly affected the plasma homocysteine level but did not alter the arterio-venous ratio.

Adult↗
PubMed2001

Lipid peroxidation is increased in paraoxonase L55 homozygotes compared with M-allele carriers.

Human serum paraoxonase (PON) is an antioxidative enzyme, which circulates on high-density lipoproteins and appears to use oxidized phospholipids as physiological substrates. PON M/L55 substitution changes the ability of PON to prevent lipid oxidation. Urinary 8-iso-PGF(2alpha) (one of F2 -isoprostanes) may represent a non-invasive in vivo index of free radical generation and we propose that PON might influence the biosynthesis of 8-iso-PGF(2alpha) in the vasculature. We studied the urinary excretion of 8-iso-PGF(2alpha) and related it to PON M/L55 genotypes in patients with type 2 diabetes mellitus (n = 55) and non-diabetic control subjects (n = 55). Urinary 8-iso-PGF(2alpha) was determined by competitive ELISA and the PON genotype by a PCR based restriction enzyme digestion method. LL homozygotes were compared to M-allele carriers (ML heterozygotes and MM homozygotes). The urinary excretion of 8-iso-PGF(2alpha) among non-diabetic non-smoking LL homozygotes was 3995.5 +/- 3352.8 ng/24-hour and among M-allele carriers 1689.8 +/- 1051.3 ng/24-hour (p = 0.017, ANCOVA; gender, hypertension, total cholesterol, triglycerides and LDL cholesterol as covariates). The excretion of 8-iso-PGF(2alpha), was increased in type 2 diabetes mellitus compared to non-diabetic control subjects. PON may thus protect against oxidative stress by destroying some biologically active lipids. Excretion of 8-iso-PGF(2alpha) is increased in type 2 diabetes, which may reflect oxidant injury.

Aryldialkylphosphatase↗
PubMed1999

Evaluation of plasma cystatin C as a marker for glomerular filtration rate in patients with type 2 diabetes.

AIM: To evaluate plasma cystatin C as a marker of the glomerular filtration rate in patients with type 2 diabetes and their age and sex-matched controls. MATERIALS AND METHODS: Forty-seven patients with one decade of type 2 diabetes and 51 non-diabetic control subjects were studied. Plasma cystatin C was measured by particle-enhanced turbidimetric immunoassay in a new application for the Hitachi 704 analyzer. For comparison, plasma creatinine and creatinine clearance were measured. The plasma clearance of 51Cr-EDTA by the single injection method was utilized as reference. RESULTS: In patients with type 2 diabetes the correlation coefficient between plasma cystatin C and the plasma clearance of 51Cr-EDTA was 0.774 (Spearman's coefficient) and that between plasma creatinine and the plasma clearance of 51Cr-EDTA was 0.556 (p = 0.001 for the difference). The correlation between creatinine clearance and the plasma clearance of 51Cr-EDTA was 0.411. In receiver operating characteristic (ROC) curve analysis the diagnostic accuracy of plasma cystatin C was significantly better than that of plasma creatinine (p = 0.047) or creatinine clearance (p = 0.001). The best diagnostic efficiency (98%) for cystatin C was obtained when the cut-off limit was set at 1.32 mg/l. In the control group the correlation coefficients were: between cystatin C and the plasma clearance of 51Cr-EDTA 0.627, between creatinine and the plasma clearance of 51Cr-EDTA 0.466 and between creatinine clearance and the plasma clearance of 51Cr-EDTA 0.416. The area under the ROC plot curve of cystatin C was also greatest in the control group, but the diagnostic accuracy of cystatin C was marginally better than that of either plasma creatinine (p = 0.05) or creatinine clearance (p = 0.08). Among the control subjects various non-renal causes may have interfered with cystatin C concentrations reducing the correlations. CONCLUSIONS: Cystatin C measurement is a more sensitive and specific test for GFR in patients with type 2 diabetes than plasma creatinine or its clearance, when GFR is normal or only slightly reduced. If an elevated cystatin C concentration is found, non-renal factors have to be excluded. The turbidimetric application described here can easily be applied for most clinical chemistry analyzers and is therefore useful in daily clinical practice.

Aged↗
PubMed1999

[Blue lips].

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Adolescent↗
PubMed1998

Susceptibility of LDL to oxidation is not associated with the presence of coronary heart disease or renal dysfunction in NIDDM patients.

Coronary heart disease (CHD) is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM) and the oxidation of low-density lipoprotein (LDL) may be an essential factor in the development of atherosclerotic lesions. Therefore, we studied the in vitro susceptibility of LDL to copper-induced oxidation in 72 NIDDM patients and 94 well-matched non-diabetic control subjects. There was no significant difference in the lagtime of LDL oxidation between NIDDM patients and control subjects (68.1+/-8.8 vs. 66.7+/-9.2 min, respectively, P=0.29). The plasma alpha-tocopherol/LDL-ratio was the most significant determinant of the lagtime in multiple regression analysis. High level of serum triglycerides was associated with decreased lagtime in control subjects, but not in NIDDM patients. Blood glucose balance was not associated with LDL susceptibility to oxidation in NIDDM patients. Subjects with CHD did not have LDL susceptibility to oxidation different from that of subjects without CHD in either of the study groups. Urinary albumin excretion or glomerular filtration rate was not associated with the lagtime of LDL oxidation in NIDDM patients. In conclusion, these data suggest that diabetes and hyperglycemia per se do not affect the susceptibility of LDL to oxidation. The presence of CHD or renal dysfunction were not associated with LDL susceptibility to oxidation.

Aged↗
PubMed1998

Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM.

The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been shown to be associated with cardiovascular and renal diseases in diabetes mellitus, but the mechanism underlying this association is not known. In addition, recent studies of the effect of the ACE gene on blood pressure have yielded conflicting results. Therefore, we studied the association of the ACE gene I/D polymorphism with glucose intolerance and insulin resistance, and the contribution of this locus to genetic susceptibility to hypertension in non-insulin-dependent diabetic mellitus (NIDDM). We analysed the ACE genotype in 84 unrelated NIDDM patients with a known disease duration of less than 1 year and in 115 age- and sex-matched controls. The I/D polymorphism was determined by the polymerase chain reaction. There were no differences in ACE genotype distribution and allele frequencies between patients with NIDDM and nondiabetic controls. The frequencies of the D and I alleles in both groups were identical, viz., 0.65 and 0.35, respectively. The NIDDM patients with the DD genotype had significantly higher blood glucose levels in the oral glucose tolerance test than those with the other genotypes; the incremental glucose area under the curve in the order of II, ID, and DD was 7.2+/-2.4, 9.2+/-4.0, and 10.7+/-2.7 mmol/l x h (II vs ID vs DD, P=0.0066 by ANOVA). No significant difference was found between the ACE genotype and serum insulin values. Similarly, there were no differences in body mass index, blood pressure, or serum lipids between the three genotypes. Among the non-diabetic controls, there was no statistically significant association of the I/D polymorphism with serum lipids, blood glucose levels, serum insulin concentrations, or blood pressure values. In conclusion, NIDDM patients with the DD genotype have higher blood glucose levels and are more glucose intolerant; this may help to explain the reported association between the D allele and vascular complications in NIDDM.

Diabetes Mellitus, Type 2↗
PubMed1998

Angiotensin-converting enzyme gene polymorphism is associated with coronary heart disease in non-insulin-dependent diabetic patients evaluated for 9 years.

The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE levels. Recent studies have found the ACE D allele to be associated with an increased risk for coronary heart disease (CHD) in diabetic and nondiabetic subjects. This association has not been evaluated in prospective studies. We therefore studied the relationship between ACE gene I/D polymorphism and CHD in patients with non-insulin-dependent diabetes mellitus (NIDDM) evaluated for 9 years. The I/D polymorphism was determined by polymerase chain reaction (PCR). Overestimation of the frequency of the DD genotype was eliminated by insertion-specific primers and inclusion of 5% dimethylsulfoxide (DMSO). Eighty-three patients were evaluated for a mean period of 9.1 years (range, 7.4 to 10.5). Among them, 64 patients showed no CHD at entry. During the follow-up period, 21 patients (37.5%) developed CHD. The systolic blood pressure (P = .046), fasting blood glucose (P < .01), and prevalence of hypertension (P < .001) increased, while high-density lipoprotein (HDL) cholesterol (P < .001) decreased. Patients who developed CHD were older than those who did not; the mean age was 59.3 and 53.2 years, respectively (P = .003). The prevalence of albuminuria at follow-up examination was higher in CHD subjects versus non-CHD subjects (61.9% v 20.9%, P = .012). The D allele of the ACE gene was significantly more frequent in subjects with CHD versus those without CHD in both follow-up (P = .028, chi2 test) and cross-sectional (P = .033, chi2 test) settings. No difference could be detected between the three genotypes in age, body mass index (BMI), blood pressure, or plasma lipid levels. In our logistic regression analysis, the best model selected the DD genotype (P = .0105) and age (P = .0407) as significant risk factors for CHD. This model classified 89% of the subjects correctly. In conclusion, this 9-year prospective study supports the hypothesis that the ACE I/D polymorphism is an important and independent risk factor for CHD in patients with NIDDM.

Adult↗
PubMed1998

The association between the total antioxidant potential of plasma and the presence of coronary heart disease and renal dysfunction in patients with NIDDM.

Oxidative stress may be an important pathogenetic factor in the development of diabetic vascular complications. The total antioxidative potential of plasma reflects the ability of an individual to resist oxidative stress. We measured the plasma total peroxyl radical-trapping potential (TRAP) and the concentrations of four plasma chain-breaking antioxidants in 81 patients with non-insulin-dependent diabetes mellitus (NIDDM) nine years after diagnosis and in 102 well-matched non-diabetic control subjects. The association between the total antioxidative potential and the presence of coronary heart disease (CHD) and diabetic kidney disease were also studied. There were no significant differences in plasma TRAP between NIDDM patients and control subjects (1250+/-199 vs. 1224+/-198 microM). Nor were there any significant differences in the concentrations of plasma uric acid, ascorbic acid, alpha-tocopherol, and protein thiols between NIDDM patients and control subjects. Patients with a low glomerular filtration rate and/or high urinary albumin excretion had elevated plasma uric acid. Plasma TRAP was not, however, associated with renal dysfunction. The plasma of NIDDM patients with CHD had a significantly higher value of unidentified antioxidative potential than that of patients without CHD. This relation was strongly dependent upon smoking. In conclusion, these data demonstrate that there are no major defects in the antioxidative potential of plasma caused by NIDDM per se. CHD and diabetic renal dysfunction were not associated with changes in plasma TRAP.

Aged↗
PubMed1998

Angiotensin-converting enzyme insertion/deletion polymorphism and diabetic albuminuria in patients with NIDDM followed Up for 9 years.

Nephropathy is a major cause of premature morbidity and mortality in patients with non-insulin-dependent diabetes mellitus (NIDDM). The insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) is a genetic determinant of plasma ACE levels. Recent studies have found I/D polymorphism of the ACE gene to be associated with nephropathy in NIDDM. This association has not been evaluated in prospective studies. We, therefore, studied the relationship between ACE gene I/D polymorphism and diabetic albuminuria and glomerular filtration rate (GFR) in 83 NIDDM patients followed up for 9 years. At baseline, 29% (24 of 83) of the diabetic patients had an increased (>30 mg/24 h) urinary albumin excretion rate (UAER) and the prevalence of albuminuria at the 9-year examination was 35% (29 of 83). During the follow-up period, systolic blood pressure (p = 0.044), prevalence of hypertension (p < 0.01), and fasting blood glucose levels (p < 0.01) increased, while high-density lipoprotein cholesterol (p < 0.01) decreased. The declines of GFR during the follow-up period were 8.5, 14.1, and 16.3% within genotype groups of II, ID, and DD, respectively (p values for decreases: NS for II, <0.001 for ID, and <0.001 for DD). Patients with the DD genotype tended to have a steeper decrease of GFR, but the change was not statistically significant between the genotype groups. The increases of UAER during the follow-up period were 35.1, 8.3, and 122.4% within genotype groups of II, ID, and DD, respectively, but p values for all increases were not significant. Parallel to GFR, patients with the DD genotype tended to have a steeper increase of UAER, but the change was not statistically significant between the genotype groups. There were no differences in the ACE genotype distribution and allele frequencies between the patients with or without albuminuria either at follow-up or in cross-sectional settings. In conclusion, this 9-year follow-up study does not support the hypothesis that the ACE I/D polymorphism is a major genetic marker of diabetic nephropathy in NIDDM patients.

Adult↗
PubMed1998

Mutation C677T of methylenetetrahydrofolate reductase gene is not associated with coronary artery disease, but possibly with albuminuria, in type 2 diabetic patients.

The missense mutation in the 677th nucleotide (C677T) of methylenetetrahydrofolate reductase gene causes substitution of valine (V) for alanine (A) resulting in three genotypes VV, VA and AA. The VV genotype causes hyperhomocysteinemia and may be a risk factor for coronary artery disease. We determined genotypes by polymerase chain reaction and subsequent restriction fragment length analysis and compared them in 84 patients with type 2 diabetes and in 115 non-diabetic subjects with and without coronary disease. Fractional urinary excretion rate of albumin was assessed by nephelometry. The VV, VA, and AA frequencies in the diabetic and in the control groups were 0.095, 0.357, 0.548 and 0.061, 0.417, 0.522, respectively (p = NS, diabetic vs. controls, chi2 test). Genotype frequencies did not differ in either diabetic or control subjects between those with or those without coronary disease (chi2 test). The fractional urinary excretion rate of albumin (mean +/-SD) in diabetic patients with the VV genotype i.e. 1.59 +/-0.71 was lower (Kruskall-Wallis test p = 0.002) than in the other genotypes i.e. VA 5.98 +/-9.75 and AA 3.75 +/-4.77, respectively (post-hoc Mann-Whitney test VV vs. VA p = 0.005 and VV vs. AA p = 0.054, respectively). We found that in patients with type 2 diabetes the methylenetetrahydrofolate reductase VV genotype was associated with a low urinary albumin excretion but not with coronary artery disease or diabetes per se.

Adult↗
PubMed1998

The level of autoantibodies against oxidized LDL is not associated with the presence of coronary heart disease or diabetic kidney disease in patients with non-insulin-dependent diabetes mellitus.

Oxidation of low-density lipoprotein (LDL) may be an important factor in the development of diabetic macrovascular and renal complications. The level of autoantibodies against oxidized LDL (oxLDL-Ab) can be used as an index of LDL oxidation in vivo. The purpose of this study was to investigate the association between the level of oxLDL-Ab and the presence of coronary heart disease and renal dysfunction in patients with non-insulin-dependent diabetes mellitus (NIDDM). We determined the plasma levels of oxLDL-Ab in 46 NIDDM patients and 48 well matched nondiabetic control subjects. NIDDM patients had a moderately higher level of oxLDL-Ab than control subjects (0.083 +/- 0.051 vs. 0.062 +/- 0.045, p = 0.04). However, there was no difference in the level of oxLDL-Ab between subjects with and without coronary heart disease, and the level of oxLDL-Ab was not associated with indices of glomerular filtration rate or urinary albumin excretion.

Aged↗
PubMed1997

New biomarker evidence of oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus.

Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. We have investigated oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus (NIDDM) by urinary 8-OHdG assessments. We determined the total urinary excretion of 8-OHdG from 24 h urine samples of 81 NIDDM patients 9 years after the initial diagnosis and of 100 non-diabetic control subjects matched for age and gender. The total 24 h urinary excretion of 8-OHdG was markedly higher in NIDDM patients than in control subjects (68.2 +/- 39.4 microg vs. 49.6 +/- 37.7 microg, P = 0.001). High glycosylated hemoglobin was associated with a high level of urinary 8-OHdG. The increased excretion of urinary 8-OHdG is seen as indicating an increased systemic level of oxidative DNA damage in NIDDM patients.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1997

Fast 5-hour determination of angiotensin-converting enzyme genotypes from blood by SDS-PAGE using PhastSystem.

Polymorphism in the angiotensin-converting enzyme (ACE) gene has been shown to correlate with circulating ACE concentrations in plasma, and also to be an independent risk factor in the development of many cardiovascular diseases. However, methods available today for ACE genotyping are still laborious and time-consuming. Here we report a sensitive, simple and non-isotopic procedure with commercially available gels for the identification of ACE insertion/ deletion polymorphism. This technique includes rapid extraction of the DNA by the QIAamp Blood Kit prior to polymerase chain reaction, followed by sodium dodecylsulphate polyacrylamide gel electrophoresis using the PhastSystem (Pharmacia). The procedure can be accomplished in five-hours from drawing the blood samples to the final result.

Aged↗
PubMedDate not supplied

Association between M/L55-polymorphism of paraoxonase enzyme and oxidative DNA damage in patients with type 2 diabetes mellitus and in control subjects.

The paraoxonase enzyme (PON) gene polymorphism causes a change of methionine (M-allele) to leucine (L-allele). PON may reduce low density lipoprotein oxidation and prevent atherosclerosis. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive index of oxidative DNA damage. We have studied the association between the PON genotypes and the urinary excretion of 8-OHdG. The study population consisted of 93 Finnish type 2 diabetes patients and 106 non-diabetic control subjects. The 24-h excretion of 8-OHdG was significantly higher in diabetic patients than in control subjects (P < 0.001). In control subjects, the ratio of the 8-OHdG/glomerular filtration rate increased in order of genotype from MM to ML to LL (P < 0.0412). These results suggest that lipid peroxidation may have an effect on DNA oxidation.

8-Hydroxy-2'-Deoxyguanosine↗