vitamin-b-12 and Albuminuria

Diabetes is a leading cause of end-stage kidney disease (ESKD) mainly due to development and progression of diabetic kidney disease (DKD). In absence of definitive treatments of DKD, small studies showed that vitamin B may help in delaying progression of DKD by inhibiting vascular inflammation and endothelial cell damage. Hence, it could be beneficial as a treatment option for DKD.. To assess the benefits and harms of vitamin B and its derivatives in patients with DKD.. We searched the Cochrane Renal Group's Specialised Register to 29 October 2012 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.. We included randomised controlled trials comparing vitamin B or its derivatives, or both with placebo, no treatment or active treatment in patients with DKD. We excluded studies comparing vitamin B or its derivatives, or both among patients with pre-existing ESKD.. Two authors independently assessed study eligibility, risk of bias and extracted data. Results were reported as risk ratio (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes. Statistical analyses were performed using the random-effects model.. Nine studies compared 1354 participants randomised to either vitamin B or its derivatives with placebo or active control were identified. A total of 1102 participants were randomised to single vitamin B derivatives, placebo or active control in eight studies, and 252 participants randomised to multiple vitamin B derivatives or placebo. Monotherapy included different dose of pyridoxamine (four studies), benfotiamine (1), folic acid (1), thiamine (1), and vitamin B12 (1) while combination therapy included folic acid, vitamin B6, and vitamin B12 in one study. Treatment duration ranged from two to 36 months. Selection bias was unclear in three studies and low in the remaining six studies. Two studies reported blinding of patient, caregiver and observer and were at low risk of performance and detection bias, two studies were at high risk bias, and five studies were unclear. Attrition bias was high in one study, unclear in one study and low in seven studies. Reporting bias was high in one study, unclear in one study, and low in the remaining seven studies. Four studies funded by pharmaceutical companies were judged to be at high risk bias, three were at low risk of bias, and two were unclear.Only a single study reported a reduction in albuminuria with thiamine compared to placebo, while second study reported reduction in glomerular filtration rate (GFR) following use of combination therapy. No significant difference in the risk of all-cause mortality with pyridoxamine or combination therapy was reported. None of the vitamin B derivatives used either alone or in combination improved kidney function: increased in creatinine clearance, improved the GFR; neither were effective in controlling blood pressure significantly compared to placebo or active control. One study reported a significant median reduction in urinary albumin excretion with thiamine treatment compared to placebo. No significant difference was found between vitamin B combination therapy and control group for serious adverse events, or one or more adverse event per patient. Vitamin B therapy was reported to well-tolerated with mild side effects in studies with treatment duration of more than six months. Studies of less than six months duration did not explicitly report adverse events; they reported that the drugs were well-tolerated without any serious drug related adverse events. None of the included studies reported cardiovascular death, progression from macroalbuminuria to ESKD, progression from m. There is an absence of evidence to recommend the use of vitamin B therapy alone or combination for delaying progression of DKD. Thiamine was found to be beneficial for reduction in albuminuria in a single study; however, there was lack of any improvement in kidney function or blood pressure following the use of vitamin B preparations used alone or in combination. These findings require further confirmation given the limitations of the small number and poor quality of the available studies.

Topics: Albuminuria; Diabetic Nephropathies; Folic Acid; Humans; Pyridoxamine; Randomized Controlled Trials as Topic; Selection Bias; Thiamine; Vitamin B 12; Vitamin B 6; Vitamin B Complex; Vitamins

Type 2 diabetes mellitus (T2DM) is a worldwide pandemic that may lead to diabetic kidney disease (DKD), a complication which is the single most important and globally prevalent cause of chronic kidney disease. Microalbuminuria has been shown to be an early indicator of DKD and data suggest that angiotensin receptor blockers (ARBs) reduce urinary albumin excretion and retard the progression of renal disease in hypertensive T2DM patients. However, the effects of ARBs on preventing microalbuminuria and ensuing DKD in normotensive patients with T2DM is yet to be fully established. The objective of this study is to assess the anti-microalbuminuric effects of losar-tan therapy versus placebo in normotensive T2DM patients. This randomized single blinded controlled trial was performed at the Diabetic Clinic, Jinnah Hospital, Lahore over a period of 10 months. A total of 361 normotensive patients with T2DM and microalbuminuria were selected; of them, 171 patients were randomly allocated to the test group and 190 enrolled into the control group. The patients in the test group were started on losartan 50 mg/day for a six month period while those in the control group were put on vitamin B-12 500 mcg/day. The patients as well as the primary attending phy-sicians/lab evaluators were blinded to the study. All study patients were followed up on a monthly basis. Quantitative microalbuminuria was tested at the beginning and at the end of the study. Out of the 171 patients in the test group, 149 (87.1%) had significant reduction of albuminuria by > 30% of their baseline (mean 101.9 +/- 21.7 baseline and, 47.5 +/- 12.9 post-therapy). The corresponding values for albuminuria in the 190 patients in the control group was mean 104.7 +/- 26.3 baseline and post 6-month mean 103.9 +/- 22.9, with P< 0.0001. The anti-albuminuric effect of losartan was reversible as seen on re-checking the urinary albumin two months after discontinuation of treatment. Our study shows that losartan was well tolerated and demonstrated significant anti-proteinuric effects in patients with T2DM with early nephropathy independent of hypertension.

Topics: Adult; Aged; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Losartan; Male; Middle Aged; Single-Blind Method; Time Factors; Treatment Outcome; Vitamin B 12; Vitamins

Folate, vitamin B. Population-based prospective cohort study from fetal life onward.. This study was performed among 4,226 pregnant women and their children.. At the median age of 6.0 (IQR, 5.9-6.3) years, we measured combined kidney volume with ultrasound, estimated glomerular filtration rate based on creatinine (eGFR. We observed that higher maternal folate concentrations were associated with larger childhood combined kidney volume, whereas higher maternal vitamin B. Observational study, so causality cannot be established.. Our findings suggest that folate, vitamin B

Topics: Albuminuria; Child; Child, Preschool; Cohort Studies; Female; Fetal Blood; Folic Acid; Follow-Up Studies; Glomerular Filtration Rate; Homocysteine; Humans; Infant; Infant, Newborn; Kidney Function Tests; Male; Maternal-Fetal Exchange; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Vitamin B 12

Diabetic Mellitus is the chronic metabolic disorder associated with various complications of heart, eyes, nerves, kidney etc. Diabetic Nephropathy is one of the leading causes of death in diabetic patient. We hypothesized that decrease Vitamin B. Our study population consist of 100 subjects out of which 50 cases of Diabetes Mellitus without Diabetic Nephropathy and 50 cases of Diabetes Mellitus with Diabetic Nephropathy. We measured various routine lab parameters, apart from it, we measured spot urinary albumin to creatinine ratio to assess diabetic nephropathy and in special investigation we measured serum Vitamin B. Our study points towards the decrease levels of serum Vitamin B

Topics: Albuminuria; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; India; Vitamin B 12; Vitamin B 12 Deficiency

To investigate the vitamin B status, with particular focus on vitamin B6, in adults with and without incipient nephropathy secondary to type 2 diabetes mellitus.. Plasma and/or urine concentrations of vitamins B₆, B₁, B₁₂, related vitamers and biomarkers (including total homocysteine, methylmalonic acid) were measured in 120 adults with type 2 diabetes (including 46 patients with microalbuminuria) and 52 non-diabetic control subjects.. Plasma concentrations of pyridoxal 5'-phosphate (PLP) were significantly lower in patients with type 2 diabetes than in control subjects (median: 22.7 nmol/L, diabetes with microalbuminuria; 26.8 nmol/L, diabetes without microalbuminuria; 39.5 nmol/L, non-diabetic control; p<0.0001). The prevalence of low PLP (<30 nmol/L) was 63%, 58%, and 25% in the diabetes groups with and without microalbuminuria and the control group, respectively. Plasma levels of pyridoxine and pyridoxal were also lower (p<0.0001), but levels of pyridoxamine, pyridoxamine 5'-phosphate, and pyridoxic acid were higher in both groups with diabetes compared to the control group (p<0.001). Thiamine deficiency was highly prevalent in all groups, whereas low vitamin B₁₂ and elevated methylmalonic acid were rare. Increased levels of C-reactive protein and soluble vascular cell adhesion molecule-1 were observed in the groups with diabetes (p<0.05, versus healthy control).. Deficiency of vitamin B₆ (PLP, pyridoxine, pyridoxal) and vitamin B₁ (thiamine) was prevalent in type 2 diabetes. Incipient nephropathy was associated with more pronounced alterations in vitamin B₆ metabolism and stronger indications of endothelial dysfunction and inflammation.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Inflammation; Male; Middle Aged; Pyridoxic Acid; Thiamine; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Vitamin B 6 Deficiency; Young Adult

Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort.. We analyzed participants from the Framingham Heart Study (n = 2965, mean age 58 years, 53% female) who provided samples for plasma B12. Logistic regression models adjusted for covariates including homocysteine were constructed to test the association between B12 and prevalent albuminuria (UACR ≥17 mg/g [men] and ≥25 mg/g [women]) and reduced kidney function (defined as an eGFR < 60 ml/min/1.73 m(2), RKF). Because of a significant interaction between B12 and homocysteine in the prevalent RKF model (p = 0.005), the model was stratified by the median homocysteine levels. Logistic regression models were constructed to test the association between B12 and incident albuminuria and RKF. The results were replicated in 4445 participants from NHANES 2003-2004.. Baseline B12 levels ranged from 50-1690 pg/ml. Elevated B12 was associated with prevalent albuminuria (OR 1.44 per 1 SD increase, 95% CI 1.10-1.87) and RKF (OR 1.83, 95% CI 1.30-2.60). However after stratifying by median homocysteine levels, this relationship remained only in the higher homocysteine stratum. There was no association between B12 and incident albuminuria (OR 1.17, 95% CI 0.79 - 1.73) or RKF (OR 1.45, 95% CI 0.97 - 1.88). In the NHANES cohort, elevated B12 was associated with RKF after full covariate adjustment (OR 3.06, 95% CI 2.30-4.08). There was no association with albuminuria.. In participants with high baseline homocysteine levels, increased plasma B12 was associated with RKF.

Topics: Adult; Aged; Albuminuria; Biomarkers; Cohort Studies; Female; Glomerular Filtration Rate; Homocysteine; Humans; Kidney Function Tests; Logistic Models; Male; Middle Aged; Nutrition Surveys; Predictive Value of Tests; Prognosis; Renal Insufficiency; Risk Assessment; Vitamin B 12

Rates of renal and cardiovascular disease are high among Aboriginal Australians living in remote communities. Nutritional problems, in particular low folate levels, are also common. This suggests that increased homocysteine concentrations might be widespread, and a possible contributor to the high rates of cardiovascular disease.. To examine homocysteine concentrations, and their relationships to folate levels, and to markers of renal disease and cardiovascular disease in a remote Aboriginal Australian community. As part of a cross-sectional survey among adults in one community, homocysteine concentrations, concentrations of the crucial determinants (red blood cell (RBC) folate, vitamin B(12) and the C677T methylene tetrahydrofolate reductase polymorphism) and cardiovascular risk factors were examined.. Among 221 people, geometric mean homocysteine concentration was 11.8 micromol/L (range: 11.1-12.5 micromol/L), with 57/221 (26%) values > or =15.0 micromol/L. Higher concentrations were associated with older age, male gender, lower RBC folate and lower vitamin B(12) concentrations and homozygosity for C677T. Homocysteine concentrations were not related to the presence of albuminuria, other than over the overt albuminuria range. Homocysteine concentrations were inversely correlated with calculated glomerular filtration rate (GFR). Carotid intima-media thickness, however, was not related to homocysteine concentration. In multivariate analyses, age, male gender, lower RBC folate concentrations, lower vitamin B(12) concentrations, lower calculated GFR and the C677T polymorphism were all associated with homocysteine concentrations.. Homocysteine concentrations were consistent with previous limited reports in Aboriginal communities. Although superficially they are similar to reports from non-Aboriginal settings, the younger age of this cohort and the association of homocysteine concentrations with age suggest that age-specific concentrations are higher among Aboriginal Australians. In addition to dietary determinants, the high prevalence of apparently reduced renal function renal disease appears to be an important determinant of homocysteine concentrations in remote Aboriginal communities. The role of homocysteine concentrations as a potential mediator of the high rates of cardiovascular disease remains to be determined.

Topics: Adult; Albuminuria; Arteriosclerosis; Australia; Cardiovascular Diseases; Cross-Sectional Studies; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Kidney Diseases; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Native Hawaiian or Other Pacific Islander; Polymorphism, Genetic; Regression Analysis; Rural Population; Vitamin B 12

The role of the renal apical brush-border membrane (BBM) endocytic receptors cubilin and megalin in the onset of albuminuria in rats exposed to a single dose of total body irradiation (TBI) has been investigated. Albuminuria was evident as immunoblot (IB) analysis of the urine samples from TBI rats revealed excretion of large amounts of albumin. IB analysis of the BBM proteins did not reveal any significant changes in cubilin or megalin levels, but (125)I-albumin binding to BBM from TBI rats declined by 80% with a fivefold decrease (from 0.5 to 2.5 microM) in the affinity for albumin. IB analysis of cubilin from the BBM demonstrated a 75% loss when purified using albumin, but not intrinsic factor (IF)-cobalamin (Cbl) ligand affinity chromatography. Immunoprecipitation (IP) of Triton X-100 extract of the BBM with antiserum to cubilin followed by IB of the immune complex with an antiserum to megalin revealed a 75% loss of association between megalin and cubilin. IP studies with antiserum to cubilin or megalin and IB with antiserum to the cation-independent mannose 6-phosphate/insulin-like growth factor II-receptor (CIMPR) revealed that CIMPR interacted with both cubilin and megalin. In addition, TBI did not disrupt the association of CIMPR with either cubilin or megalin in BBM. These results suggest that albuminuria noted in TBI rats is due to selective loss of albumin and megalin, but not CIMPR or IF-Cbl binding by cubilin. Furthermore, these results also suggest that albumin and IF-Cbl binding to cubilin occur at distinct sites and that in the rat renal BBM, CIMPR interacts with both cubilin and megalin.

Topics: Albuminuria; Animals; Binding, Competitive; Chromatography, Affinity; Immunoblotting; Intrinsic Factor; Kidney; Low Density Lipoprotein Receptor-Related Protein-2; Male; Microvilli; Precipitin Tests; Protein Binding; Rats; Rats, Inbred Strains; Receptor, IGF Type 2; Receptors, Cell Surface; Serum Albumin; Vitamin B 12; Whole-Body Irradiation

The aim of this study was to investigate the relationship between total homocysteine levels in people with Type 2 diabetes and cognitive status. Fifty patients from our diabetes unit (30 females/20 males) with diabetes were enrolled. All patients had fasting blood samples taken for measurement of cardiovascular risk factors; total cholesterol and triglyceride concentrations and other lipid fractions (lipoprotein (a), low density lipoprotein (LDL-cholesterol), high density lipoprotein (HDL-cholesterol)), glucose, HbA(1c) and homocysteine. 24-h urine collection was used to measure creatinine clearance and microalbuminuria. Vitamin B-12 and folate were measured to assess vitamin status. All diabetic patients were assessed for late complications and a Mini-Mental State Examination (MMSE) was performed. The patients were 64.6 (49-78) years old with body mass index (BMI) of 29.6 +/- 6.3 kg/m(2), and duration of diabetes of 8.9 +/- 6.7 years. A univariant correlation analysis was performed among cardiovascular risk factors and vitamins with total MMSE score. Total homocysteine was inverse by correlated with MMSE score (r=-0.38; P<0.05) of the other measures of cardiovascular risk, microalbuminuria showed an inverse correlation with MMSE score (r=-0.51:P<0.01). Lipoproteins, glucose control and vitamin status were not correlated MMSE score. In the multiple regression model only microalbuminuria remained in the model, showing a decrease of one point in the MMSE result with each milligram of microalbuminuria, adjusted for confounding factors. Cognitive status in type 2 diabetic was correlated with homocysteine levels and microalbuminuria, this last endothelial damage marker remaining as an independent risk factor of cognitive deterioration.

Topics: Aged; Albuminuria; Cholesterol; Cognition; Cognition Disorders; Diabetes Mellitus, Type 2; Female; Folic Acid; Glycated Hemoglobin; Homocysteine; Humans; Lipoproteins; Male; Middle Aged; Triglycerides; Vitamin B 12

Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS).. We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991-1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995-1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 micromol/l in each phenotypic category and differences between categories were assessed with regression models.. The mean age of the subjects was 54 years (range 28-82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 micromol/l) and those without (9.4 micromol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 micromol/l) compared with those with 1 or no phenotype (9.3 micromol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007).. Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Albuminuria; Blood Glucose; Coronary Disease; Creatinine; Fasting; Female; Folic Acid; Glucose Tolerance Test; Homocysteine; Humans; Insulin; Insulin Resistance; Male; Massachusetts; Middle Aged; Risk Factors; Sex Factors; Vitamin B 12

Although it is accepted that elevated plasma homocysteine (tHcy) levels occur in end-stage renal disease and type 2 diabetes, the changes with milder renal dysfunction (e.g., microalbuminuria) are less clearly established. This study explores the relationship among tHcy, creatinine clearance (Ccr), and albumin excretion rate (AER) in a population with type 2 diabetes.. A total of 260 patients with type 2 diabetes were screened in our outpatient clinic during 10 months. Fasting blood samples were collected, and AER was calculated from an overnight timed urine sample. Ccr was calculated using the Cockroft-Gault formula.. A total of 198 subjects (76%) had normoalbuminuria (<20 microg/min), 50 subjects (19%) had microalbuminuria (20-200 microg/min), and 12 subjects (5%) had macroalbuminuria (>or=200 microg/min). Those with microalbuminuria had higher levels of tHcy than those with normoalbuminuria (13.2 +/- 7.8 vs. 11.3 +/- 4.6 micromol/l, P < 0.05). Patients were then subdivided based on low Ccr (<80 ml x min(-1) x 1.73 m(-2)) and normal Ccr (>or=80 x min(-1) x 1.73 m(-2)). None of the patients with macroalbuminuria had normal Ccr. In those with normoalbuminuria, tHcy levels were higher than in those with low Ccr than in those with normal Ccr (12.0 +/- 4.6 vs. 10.0 +/- 4.4 micromol/l, P < 0.01). The same was found for those with microalbuminuria (low Ccr versus normal Ccr: 14.6 +/- 9.0 vs. 10.2 +/- 2.8 micromol/l, P < 0.02). For normal Ccr, tHcy was similar irrespective of AER (normoalbuminuria versus microalbuminuria: 10.0 +/- 4.4 vs. 10.2 +/- 2.8 micromol/l, NS). For low Ccr, tHcy was higher in those with microalbuminuria versus normoalbuminuria (14.6 +/- 9.0 vs. 12.0 +/- 4.6 micromol/l, P = 0.01). Using multivariate regression, Ccr, but neither AER nor the presence of albuminuria, was an independent predictor of tHcy.. These data strongly suggest that in patients with type 2 diabetes, the relationship between plasma tHcy and AER is largely due to associated changes in renal function, as defined by Ccr.

Topics: Aged; Albuminuria; Creatinine; Diabetes Mellitus, Type 2; Female; Folic Acid; Homocysteine; Humans; Male; Metabolic Clearance Rate; Middle Aged; Regression Analysis; 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

The increased cardiovascular risk in subjects with NIDDM is partly explained by an association with established risk factors like hypertension, dyslipidemia, and obesity. Mild hyperhomocysteinemia has emerged as a new risk factor for cardiovascular disease. The purpose of this study was to assess its role in NIDDM.. We studied predictors of homocysteine levels and correlations between homocysteine and (micro-)albuminuria, retinopathy, and history of cardiovascular disease in normotensive NIDDM subjects under stable metabolic control. This was done in 85 NIDDM subjects by measuring fasting and post-methionine-loading homocysteine levels together with blood pressure, BMI, serum cholesterol, triglyceride, HDL cholesterol, folate, vitamin B12, pyridoxal-5-phosphate, HbA1c, and (micro-)albuminuria and creatinine clearance in triplicate 24-h urine samples. The relationship between micro- and macrovascular complications and fasting homocysteine only was studied in an additional 65 subjects, giving a total of 150 subjects.. In multiple regression analysis, significant (P < 0.05) predictors of fasting homocysteine were low-normal values of creatinine clearance (threshold effect at < 80 ml.min-1 .1.73 m-2), folate (< 20 nmol/l), and vitamin B12 (< 350 pmol/l), and postmenopausal status in women. Determinants of post-methionine homocysteine were pyridoxal-5-phosphate levels < 80 nmol/l, creatinine clearance, and sex (higher levels in women). Hyperhomocysteinemia did not cluster with other cardiovascular risk factors, like hypertension, obesity, or dyslipidemia. Regarding cardiovascular complications, fasting homocysteine, but not post-methionine homocysteine, was higher in subjects with a history of cardiovascular disease. There was a stepwise increase in the prevalence of subjects with cardiovascular disease with increasing fasting homocysteine. The prevalence of cardiovascular disease was 19.4% in the bottom quartile of fasting homocysteine, versus 55.0% in the top quartile (P for trend < 0.01). Neither fasting homocysteine nor post-methionine homocysteine correlated with (micro-)albuminuria or with retinopathy.. The findings suggest that homocysteine levels in NIDDM rise even with modest deterioration of renal function and when vitamin status is in the low to low-normal range. Fasting homocysteine correlates with macrovascular disease, but we found no evidence of a correlation with retinopathy or (micro-)albuminuria. Post-methionine homocysteine levels do not show a correlation with micro- or macrovascular complications.

Topics: Administration, Oral; Adult; Aged; Albuminuria; Analysis of Variance; Blood Pressure; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Fasting; Female; Folic Acid; Homocysteine; Humans; Male; Methionine; Middle Aged; Postmenopause; Premenopause; Pyridoxal Phosphate; Regression Analysis; Risk Factors; Vitamin B 12

The reactive vascular-injuring amino acid homocysteine was previously shown to be increased in plasma in diabetic patients with clinical signs of nephropathy. In this study, plasma homocysteine was measured in type 1 diabetic patients with normoalbuminuria (n = 22), microalbuminuria (n = 40) and proteinuria (n = 14) in order to investigate whether plasma homocysteine levels are increased already at the stage of incipient nephropathy, i.e. microalbuminuria. Furthermore, patients were characterized according to the degree of retinopathy. Plasma homocysteine in the whole population (n = 76) was related to B-Folate (r = 0.38, p < 0.01), S-Creatinine (r = 0.55, p < 0.001), S-Urea (r = 0.37, p < 0.01), U-Albumin (r = 0.46, p < 0.001), urinary N-acetyl-beta- glucosaminidase (r = 0.40, p < 0.001), systolic blood pressure (r = 0.36, p < 0.01) and diabetes duration (r = 0.44, p < 0.001). There were no differences in plasma homocysteine levels between patients with normoalbuminuria (8.0 +/- 1.7 mumol l-1; mean +/- SD) and those with microalbuminuria (9.1 +/- 3.4 mumol l-1). However, patients with clinical signs of nephropathy had higher plasma homocysteine levels (12.9 +/- 5.7 mumol l-1, p < 0.01) compared to the other two groups. There was no association between plasma homocysteine levels and different degrees of retinopathy. Thus, the present study does not show any relation between plasma homocysteine levels and early stages of diabetic nephropathy or retinopathy indicating that elevated concentrations of plasma homocysteine does not explain the increased risk for atherosclerosis observed in patients with microalbuminuria.

Topics: Adult; Albuminuria; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Female; Homocysteine; Humans; Male; Middle Aged; Vitamin B 12

Topics: Albuminuria; Anemia, Macrocytic; Body Height; Body Weight; Child, Preschool; Female; Humans; Intestinal Absorption; Proteinuria; Schilling Test; Thrombocytopenia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Albuminuria; Flavonoids; Humans; Rutin; Vitamin B 12; Vitamins