vitamin-b-12 and Diabetic-Angiopathies

Moderate hyperhomocysteinemia is one of risk factors for arteriosclerotic disease. In diabetic patients, hyperhomocysteinemia is an independent risk factor for macroangiopathy and mortality. Homocysteinemia is also associated with diabetic microangiopathy, silent stroke, and cognitive impairment. However, excluding those with nephropathy or microangiopathy, plasma homocysteine is lower in diabetic patients than non-diabetic controls. Oral treatment with folic acid, vitamin B12 and B6 reduces plasma homocysteine concentration about by 30%. The vitamin treatment for reduction of hyperhomocysteinemia improves endothelial dysfunction and retards carotid atherosclerosis. Few randomized control trials have showed a positive effect of the vitamin treatment on prevention from stroke and ischemic heart disease. Further prospective intervention studies are necessary to address the issue whether lowering homocysteine does prevent the development and progression of diabetic macroangiopathy.

Topics: Arteriosclerosis; Diabetic Angiopathies; Folic Acid; Humans; Hyperhomocysteinemia; Randomized Controlled Trials as Topic; Risk Factors; Vitamin B 12; Vitamin B 6

Topics: Corrinoids; Diabetic Angiopathies; Diabetic Retinopathy; Diet; Diet Therapy; Drug Therapy; Humans; Insulin; Nandrolone; Testosterone; Vitamin B 12

The aim of this study was to compare the sensitivity of three ultrasound phenotypes of carotid atherosclerosis in a longitudinal study of patients with diabetic nephropathy. B-mode ultrasound-derived intima-media thickness (IMT), total plaque area (TPA) as well as three-dimensional ultrasound (3DUS) vessel wall volume (VWV) of the common carotid artery (CCA) (VWV(CCA)) and internal carotid artery (ICA). (VWV(CCA+ICA)) were all evaluated in subjects enrolled in a randomized placebo-controlled double blind study of vitamin B therapy. Of 106 subjects randomized, 77 subjects were scanned at baseline and 2.3 +/- 1 y later (range: 0.5 to 4.5 y); of these subjects, 71 had images of sufficient quality for complete analysis of all three measurements. Subjects were analyzed according to the two treatment groups (A and B) and the analysis was performed blinded to treatment group description to prevent any potential for bias in future analyses. There were differences in sensitivity to longitudinal changes observed in all the ultrasound measurements. Specifically, there was no difference in IMT change between treatment groups (0.02 +/- 0.07 mm/y and 0.02 +/- 0.1 mm/y p = 0.15, group A and B, respectively, rates not different from zero [p > 0.05]) or TPA rate between treatment groups (0.09 +/- 0.2 cm(2)/y, significantly different from 0, p = 0.013 and -0.02 +/- 0.3 cm(2)/y in group A and B, respectively). However, the VWV(CCA+ICA) rate of change was significantly greater than 0 for group B (53 +/- 110 mm(3)/y) (p = 0.008), which was significantly (p = 0.034) higher than the rate of change of VWV(CCA+ICA) (nonsignificant, p = 0.6) for group A (-12 +/- 137 mm(3)/y). The relationship between DeltaVWV and DeltaIMT was significant, such that in group A, DeltaVWV(CCA) was positively associated with DeltaIMT (r = 0.44, p < 0.05), and in group B, DeltaVWV(CCA) was negatively correlated with DeltaIMT (r = -0.44, p < 0.01). These results suggest that 3DUS-derived VWV provides necessary and sufficient sensitivity and specificity to measure longitudinal changes in small numbers of carotid atherosclerosis patients at risk of disease progression and over short periods of time.

Topics: Aged; Carotid Artery Diseases; Carotid Artery, Common; Carotid Artery, Internal; Diabetic Angiopathies; Diabetic Nephropathies; Disease Progression; Double-Blind Method; Drug Combinations; Female; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Longitudinal Studies; Male; Middle Aged; Tunica Intima; Tunica Media; Ultrasonography; Vitamin B 12; Vitamin B 6

To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors.. In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [mum]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 microm (21.16; 75.98) and -32.15 microm (-59.09; -5.20), but high homocysteine was not (-15.11 microm (-42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors.. In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.

Topics: Aged; Brachial Artery; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Nitroglycerin; Regional Blood Flow; Risk Factors; S-Adenosylmethionine; Tetrahydrofolates; Ultrasonography; Vasodilation; Vasodilator Agents; Vitamin B 12; Vitamin B 6

Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients.. 469 ambulatory type 2 diabetes patients (mean diabetes duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)) were screened for CAN using three cardiovascular reflex tests, five minute resting heart rate (5min RHR) and heart rate variability indices.. Serum levels of vitamin B12 were significantly lower in patients treated with metformin and/or proton pump inhibitors (PPIs) compared with patients not treated (p<0.001). A 25pmol/l higher level of vitamin B12 was associated with an odds ratio of the CAN diagnosis of 0.94 (95% CI 0.88; 1.00, p=0.034), an increase in E/I-ratio of 0.21% (95% CI 0.01; 0.43, p=0.038), and a decrease in 5min RHR of 0.25 beats per minute (95% CI -0.47; -0.03, p=0.025).. Vitamin B12 may be inversely associated with CAN in patients with type 2 diabetes. Confirmatory studies investigating a causal role of vitamin B12 for the development of diabetic CAN are warranted.

Topics: Antihypertensive Agents; Autonomic Nervous System Diseases; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Diabetic Neuropathies; Female; Heart Rate; Humans; Hypertension; Hypoglycemic Agents; Male; Mass Screening; Metformin; Middle Aged; Prevalence; Proton Pump Inhibitors; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Aim of the study was to clarify the relationship between metformin-induced vitamin B12 (B12) deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes. Serum B12 concentrations, homocysteine plasma levels, the presence of retinopathy and history of macroangiopathy (stroke or coronary heart disease) were analyzed in patients without renal dysfunction (serum creatinine<115 μmol/L). Firstly, B12 status was analyzed in 62 consecutive metformin-treated patients. Secondly, the relationship between B12, homocysteine and vascular complications was analyzed in 46 metformin-treated and 38 age- and sex-matched non-metformin-treated patients. Among the 62 consecutive metformin-treated patients, B12 was deficient (<150 pmol/L) in 8 (13%) and borderline-deficient (150-220 pmol/L) in 18 (29%): the larger the metformin dosage, the lower the B12 (P=0.02, Spearman's ρ=-0.30). There were independent correlations between metformin use and B12 lowering (P=0.02, r = -0.25), and B12 lowering and elevation of homocysteine (P<0.01, r=-0.34). Elevation of homocysteine was a risk for retinopathy (P=0.02, OR 1.26, 95%CI 1.04-1.52). There was no significant relation between homocysteine and macroangiopathy. Correlation between B12 and homocysteine was stronger in metformin-treated (P<0.01, r=-0.48) than non-metformin-treated (P=0.04, r=-0.38) patients. In ten B12 deficient patients, B12 supplementation (1,500 μg/day) for 2.2±1.0 months with continued use of metformin raised B12 levels: 152±42 and 299±97 pmol/L before and after treatment, respectively (P<0.01). Metformin-induced B12 lowering in diabetes was associated with elevation of homocysteine, and hyperhomocysteinemia was independently related to retinopathy. Metformin-induced B12 deficiency was correctable with B12 supplementation.

Topics: Aged; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Dietary Supplements; Dose-Response Relationship, Drug; Female; Homocysteine; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Japan; Male; Metformin; Middle Aged; Prevalence; Risk Factors; Severity of Illness Index; Stroke; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocystinaemia is associated with macro- and microangiopathic diabetic complications. However, the role of homocysteine (Hcy), serum folate, and vitamin B12 level in the development of premature vascular damage in type 2 diabetic patients is not clear. The present study was designed to assess the relationship between total Hcy, folate, and vitamin B12 levels and arterial stiffness, an early marker of generalized atherosclerosis.. As many as 86 subjects with type 2 diabetes mellitus were studied. All participants were evaluated for glucose, HbA(1C), lipid profile, hs-CRP, endothelin, Hcy, vitamin B12, and folate. Pulse wave velocity (PWV) and augmentation index (AI) were performed as a non-invasive recording and computer analysis of the two artery sites pressure waveform using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia).. Hcy was significantly positively associated with age, serum creatinine, and vitamin B12 levels. No association between Hcy and folate was observed. The Hcy concentration was significantly positively associated with PWV (r = 0.540, p < 0.0001) and AI (r = 0.390, p < 0.0001). In a general linear model of PWV, Hcy emerged as an independent predictor of PWV even after controlling for age, creatinine, vitamin B12, and folate levels. In a multiple linear regression analysis, the association between Hcy and arterial stiffness was independent of traditional cardiovascular risk factors. Vitamin B12 levels were significantly inversely associated with tHcy (r = - 0.263, p = 0.015) and marginally associated with PWV(r = - 0.212, p = 0.052). Significant associations between folate levels and PWV were not detected.. The results lend support to the hypothesis that elevated Hcy may have a key role in the development of atherogenesis in diabetic patients. Additionally, vitamin B12 is significantly associated with tHcy concentrations and is identified as a marginally independent correlate of PWV in diabetic patients in the absence of folate deficiency.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Body Mass Index; Creatinine; Diabetes Mellitus; Diabetic Angiopathies; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Models, Biological; Overweight; Regression Analysis; Vitamin B 12

This study investigated the role of homocysteine thiolactone (HcyT) in the development of macrovascular complications in Chinese patients with type 2 diabetes. HcyT has been proposed as a possible molecular basis for homocysteine (Hcy)-induced vascular damage.. One hundred and sixty subjects were recruited into this study: 40 healthy controls and 120 patients with type 2 diabetes. Plasma Hcy levels were measured by polarization immunoassay and HcyT concentrations were monitored using high-performance liquid chromatography on a reversephase C18 column with ultraviolet detection. Plasma folic acid and vitamin B(12) levels were measured using radioimmunoassay methods.. Plasma Hcy and HcyT concentrations in patients with type 2 diabetes were significantly higher than in healthy controls (Hcy [25th and 75th quartiles]: 9.28 [7.51-11.82] vs. 5.64 [5.17-8.00] micromol/L, P=0.01; HcyT: 3.38 [2.94-4.73] vs. 2.91 [2.77-3.08] nmol/L, P<0.05). Plasma Hcy and HcyT levels in patients with macrovasculopathy (MAVP) were significantly higher compared with patients without MAVP (Hcy: 10.36 [7.67-12.45] vs. 7.85 [6.76-10.52] micromol/L, P<0.05; HcyT: 4.27 [3.02-5.11] vs. 3.12 [2.63-3.77] nmol/L, P<0.05). Plasma HcyT concentrations were positively correlated with urinary excretion of albumin/creatinine (Alb/Cr; r=0.285, P=0.007), duration of diabetes (r=0.249, P=0.019), age (r=0.233, P=0.028), and fibrinogen levels (r=0.289, P=0.034). Plasma HcyT concentrations were negatively correlated with high-density lipoprotein levels (r=-0.223, P=0.037). Binary logistic regression showed that HcyT, Hcy, smoking, serum triglyceride, and urine Alb/Cr were significantly associated with the risk of diabetic MAVP (P<0.05).. Hcy and HcyT levels were associated with the development and progression of diabetic MAVP. HcyT may provide a plausible chemical mechanism for explaining Hcy toxicity in the human vascular endothelium.

Topics: Age Factors; Asian People; Body Mass Index; China; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Folic Acid; Homocysteine; Humans; Lipids; Male; Middle Aged; Risk Factors; Smoking; Time Factors; Vitamin B 12

Individuals with Type 2 diabetes are at increased risk of stroke. Plasma homocysteine (tHcy) is an independent risk factor for cardiovascular (CV) disease. The methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism (thermolabile variant C(677)T) is associated with CV risk, partly as a result of increased Hcy, especially in homozygous subjects.. To relate the occurrence of the MTHFR polymorphism with stroke prevalence by examining allelic frequency and genotype distribution in 165 subjects with Type 2 diabetes studied for the presence of thermolabile C(677)T MTHFR mutation.. Mean age was 67.7 years, and tHcy 18.2 micromol/l. T allele frequency was 38.5%. MTHFR genotypes were: normal (CC) 40%; heterozygous (CT) 43%; homozygous (TT) 17%. Serum levels of folic acid and B12 vitamin were within normal limits. Stroke prevalence was 14%. Sixty-four per cent of stroke-free subjects had the normal C allele vs. 46% in stroke subjects. The frequencies of genotypes (CC-CT-TT) were (%): 44-41-15 in stroke-free vs. 17-57-26 in stroke patients. Coronary (CAD) and peripheral artery disease (PAD) were common in all groups, with no differences according to genotypes. Stroke prevalence was markedly higher in genotypes CT and TT (18 and 21%) compared with CC (6%). Mean tHcy levels were higher in TT subjects.. The allelic frequency of C(677)T MTHFR mutation in Type 2 diabetes subjects with stroke is markedly different from that of subjects without stroke. Genotypic characteristics suggest that C(677)T MTHFR mutation confers a higher risk for stroke to both homozygous and heterozygous T allele carriers that cannot be ascribed solely to raised tHcy and/or lower folate status in CT subjects, nor to phenotypic expression of conventional risk factors for stroke. The impact of the MTHFR polymorphism on stroke may result from T allele-linked deleterious effects, or C allele-linked protection. Confirmatory studies are warranted, as this cohort was not randomly selected, and a type 1 error cannot be ruled out.

Topics: Aged; Cohort Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Folic Acid; Gene Frequency; Heterozygote; Homozygote; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Peripheral Vascular Diseases; Polymorphism, Genetic; Risk Factors; Stroke; Vitamin B 12

The aim of this study was to examine the relation between serum total homocysteine concentrations and microvascular complications in Pima Indians with Type 2 diabetes.. Homocysteine concentrations were measured in frozen sera of 396 diabetic participants in a longitudinal study who were 40 years of age or older and who had attended one or more examinations between 1982 and 1985. Retinopathy was assessed by fundoscopy and nephropathy by an albumin:creatinine ratio greater than 300 mg/g. The incidence rate ratio for a 5 micro mol/l difference in homocysteine was calculated using proportional hazard regression.. The incidence of each complication was assessed in subjects without that complication at baseline and with more than one follow-up examination: 229 for nephropathy, 212 for retinopathy and 266 for proliferative retinopathy. There were 101 incident cases of nephropathy, 113 of retinopathy and 40 of proliferative retinopathy during a mean follow-up of 8.6, 7.5 and 8.9 years, respectively. Incidence of nephropathy was associated with homocysteine concentrations: IRR=1.42 (95% CI, 1.09-1.84, p=0.01); this remained statistically significant controlled for age, sex and duration of diabetes (p=0.03), but not when controlled for baseline renal function (p=0.4). Homocysteine concentrations were not associated with the incidence of any retinopathy IRR=1.14 (95%CI 0.89-1.46, p=0.3) but were associated with the incidence of proliferative retinopathy IRR=1.62 (95% CI 1.16-2.28, p=0.005); this association remained statistically significant when controlled for baseline renal function and diabetes duration (p=0.02).. Increased homocysteine concentrations are associated with an increased risk for incidence of nephropathy and proliferative retinopathy; the relation with incidence of nephropathy seems to be explained by an association with baseline albuminuria status concentrations, whereas the relation with incidence of proliferative retinopathy does not.

Topics: Age Factors; Analysis of Variance; Arizona; Biomarkers; Blood Glucose; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Folic Acid; Homocysteine; Humans; Incidence; Indians, North American; Longitudinal Studies; Male; Middle Aged; Vitamin B 12

Atherosclerosis is the main cause of cardiovascular morbidity and mortality in many countries. It is believed that hyperhomocysteinemia is a risk factor for premature atherosclerosis and other cardiovascular diseases (CVD) in both men and women.. Plasma samples from 31 non-CVD and 51 CVD patients with diabetes were studied. Informed consent was obtained from all subjects. Blood samples were collected after overnight fasting. Total homocysteine (H [e]), the levels of high and low density lipoproteins (HDL, LDL), total cholesterol, urea and creatinine were determined with commercial kits.. The levels of homocysteine, vitamin B12, creatinine, and urea in CVD patients were significantly higher than those found in the normal subjects. On the other hand, the levels of folic acid, HDL and LDL were lower in CVD patients than in normal subjects. Interestingly, a linear relationship was found between the levels of homocysteine and total cholesterol in CVD samples, whereas no such linear relationship was present in normal subjects.. The level of homocysteine in plasma is known to be mainly dependent on the levels of folic acid and vitamin B12. However, in the present study the level of homocysteine in the plasma of CVD patients is dependent on the level of folic acid and not on the level of vitamin B12. Subjects with high homocysteine levels should be advised to consume a folic acid-fortified diet in order to reduce the homocysteine level in patients at high risk for cardiovascular disease.

Topics: Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Female; Folic Acid; Homocysteine; Humans; Lipids; Male; Risk Factors; Vitamin B 12

The aim of this study was to determine the distribution of plasma total homocysteine (tHcy) concentrations in type 2 diabetic patients and to assess whether high tHcy values were related to chronic complications (particularly macroangiopathy and nephropathy) and/or the degree of insulin resistance.. Fasting tHcy levels were measured in 122 type 2 diabetic patients in whom the presence of chronic complications (e.g., macroangiopathy, microalbuminuria, macroproteinuria, decreased creatinine clearance, hypertension, retinopathy, and neuropathy) was recorded alongside an assessment of insulin resistance by the homeostasis model assessment (HOMA).. We found that 31% of the cohort (group 1) had raised tHcy (mean +/- 1 SD) values (20.8 +/- 5.1 micromol/l), whereas 69% (group 2) had normal values (10.2 +/- 2.0 micromol/l). The prevalence of macroangiopathy was higher in group 1 than in group 2 subjects (70 vs. 42%, P < 0.01); the prevalence of coronary artery disease was particularly higher in group 1 (46 vs. 21%, P < 0.02). The prevalence of impaired renal function, evidenced by decreased creatinine clearance, was higher in group 1 (32 vs. 10%, P < 0.005). Other clinical and biological characteristics of both groups were comparable, although group 1 had lower levels of folic acid than group 2 (5.2 +/- 2.9 vs. 7.0 +/- 3.4 ng/ml, P < 0.01). No differences were found for microalbuminuria (33 vs. 31%), retinopathy (45 vs. 42%), or neuropathy (70 vs. 59%) between groups 1 and 2, respectively The degree of insulin resistance was similar in groups 1 and 2 (46 +/- 21 and 42 +/- 20% of HOMA-insulin sensitivity) as was the assessment of beta-cell function (63 +/- 28 and 65 +/- 46%, respectively). No differences in tHcy levels were found between subjects receiving metformin and those not receiving metformin. In contrast, the plasma tHcy level was higher in diabetic patients treated with fibrates (P = 0.0016).. Elevated plasma tHcy levels in type 2 diabetes is associated with a higher prevalence of macroangiopathy and nephropathy when assessed from creatinine clearance indexes and is not associated with different degrees of insulin resistance.

Topics: Aged; Cohort Studies; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Female; Folic Acid; Homeostasis; Homocysteine; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Logistic Models; Male; Metabolic Clearance Rate; Metformin; Middle Aged; Vitamin B 12

Homocysteine is involved in a complex and dynamic system of vascular injury and repair and may thus contribute to the development of diabetic microangiopathy. This still debated issue has important scientific and clinical implications, since hyperhomocysteinemia can be corrected nutritionally.. 1) To evaluate the association between fasting plasma homocysteine, type 1 diabetes and its microvascular complications; 2) to elucidate the basis of this association by investigating the major determinants of plasma homocysteine in relation to diabetic microangiopathy.. We studied sixty-six consecutive patients with type 1 diabetes mellitus of > 10 years duration and normal serum creatinine (< 115 mumol/L, 1.3 mg/dL), and free from clinically detectable cardiovascular diseases. Forty-four non-diabetic controls were also studied. Plasma concentrations of homocysteine, folate and vitamin B12 were investigated together with the C677T mutation in the gene coding for methylenetetrahydrofolate reductase (MTHFR), a key enzyme in homocysteine metabolism. Renal and retinal diabetic complications were evaluated as albumin/creatinine ratio on early-morning, urine spot collection and fundus photographs.. Fasting plasma homocysteine levels were very similar in patients and controls. Patients with microalbuminuria or proliferative retinopathy had significantly higher values than those without: 9.4 +/- 3.1 vs 7.4 +/- 2.8 mumol/L, p < 0.02 and 9.5 +/- 2.6 vs 7.3 +/- 3.0 mumol/L, p < 0.05. This difference was not attributable to confounders, such as age, sex and smoking, nor to dissimilar plasma folate and vitamin B12 concentrations. In contrast, homozygosity for the C677T mutation in the MTHFR gene--the commonest genetic defect linked to moderately increased plasma homocysteine--was significantly more frequent in patients with microalbuminuria and/or proliferative retinopathy (50% vs 13%, p < 0.004), odds ratio 6.7 (95% CI 1.7-27.6).. Type 1 diabetes as such is not associated with increased plasma homocysteine levels, though patients with microalbuminuria and/or proliferative retinopathy display significantly higher values than those without. This difference is not attributable to obvious confounders, nor to differences in vitamin status, and may be partly mediated by genetic factors. Plasma homocysteine, together with other diabetes-related noxae, may thus be in a position to contribute to the development of nephropathy and the progression of retinopathy.

Topics: Adult; Albuminuria; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Folic Acid; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Point Mutation; Vitamin B 12

It has been postulated that the accumulation of homocysteine in plasma may induce arteriosclerosis. In order to explore the possible contribution of homocysteine to the occurrence of macroangiopathy in patients with non-insulin-dependent diabetes mellitus, the concentrations of total homocysteine in plasma were determined in 52 diabetic patients with clinical macroangiopathy, 84 diabetic patients without macroangiopathy, and 57 non-diabetic control subjects. The levels of total homocysteine in plasma were significantly higher in diabetic patients with macroangiopathy (10.8 +/- 3.8 nmol/ml) than in those without macroangiopathy (8.3 +/- 3.1 mmol/ml, P < 0.001) or non-diabetic subjects (7.5 +/- 2.1 nmol/ml, P < 0.001). Among all diabetic patients, multiple logistic regression analysis after adjustment for age, sex, and systolic blood pressure revealed that high levels of plasma homocysteine were significantly associated with the presence of diabetic macroangiopathy (P = 0.01). By an intramuscular injection of 1000 micrograms methylcobalamin daily for 3 weeks, the plasma levels of homocysteine in 10 diabetic patients were significantly decreased (14.7 +/- 7.5 vs. 10.2 +/- 6.0 nmol/ml, P < 0.01). Our results suggest that plasma homocysteine levels could be one of a number of independent risk factors for macroangiopathy in patients with diabetes mellitus and that they can be reduced by parenteral treatment with methylcobalamin.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Homocysteine; Humans; Injections, Intramuscular; Male; Middle Aged; Risk Factors; Vitamin B 12

Topics: Adolescent; Adult; Blood Vessels; Capillaries; Cobalt Isotopes; Conjunctiva; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Glomerular Filtration Rate; Humans; Injections, Intravenous; Vitamin B 12

Topics: Arteriosclerosis; Blood Chemical Analysis; Diabetes Mellitus; Diabetic Angiopathies; Geriatrics; Humans; Vitamin B 12; Vitamin B Complex