Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations or polymorphisms in the gene of the enzyme methylenetetrahydrofolate (MTHFR) are associated with hyperhomocysteinemia and possibly with an elevated risk for vascular diseases. A study was conducted on 83 individuals with type 2 diabetes in order to determine the allelic and genotypic frequencies of the G1793A mutation and to assess the effect of folic acid supplementation on plasma homocysteine concentrations. The patients were attended by the Diabetes and Hypertension Program--Balneario Camboriu/SC and received daily supplements containing 1 mg of folic acid for 3 months. DNA was previously extracted from leukocytes and the G1793A mutation was detected by PCR-RFLP. Blood samples were collected during the basal period and after supplementation for the determination of homocysteine by HPLC, and of folic acid and vitamin B(12) by RIA. The allele frequency for the G1793A mutation was 3.01% and no homozygous individuals with mutant alleles were detected. Hyperhomocysteinemia was diagnosed in 27.71% of the patients, folic acid deficiency in 15.66%, and vitamin B(12) deficiency in 7.23%. Plasma homocysteine concentrations were inversely correlated with folic acid (r = -0.27, p = 0.01) and vitamin B(12) (r = -0.21; p = 0.05) concentrations. The individuals with a heterozygous genotype for the G1793A mutation showed borderlines or deficient values in folic acid and vitamin B(12) concentrations compared to individuals with a normal genotype. Hyperhomocysteinemia and the vitamin deficiencies presented by type 2 diabetic individuals, included with a heterozygous genotype for the G1793A mutation in the MTHFR gene, reached normal values by daily folic acid supplementation.
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PMID:G1793A polymorphisms in the methylene-tetrahydrofolate gene: effect of folic acid on homocysteine levels. 1686 47

Plasma homocysteine levels are elevated in individuals with type 2 diabetes contributing to the increased cardiovascular risk of these patients. As insulin resistance is a key feature in type 2 diabetic patients, hyperhomocysteinemia might be a consequence of insulin resistance. We studied this hypothesis in 839 individuals(male: 302, female: 537, mean age: 37.5 years) with a higher prevalence of insulin resistance (positive family history of type 2 diabetes, history of gestational diabetes, overweight). Subjects with overt type 2 diabetes or known kidney disease were excluded from the study. Mean plasma homocysteine concentration was 8.9 micromol/l (95% RCI 4.8-14.9). Adjusted for age and sex we could not find a significant correlation between homocysteine levels and BMI, insulin levels, or the insulin sensitivity-index (r = 0.35; p = 0.48). Furthermore, after a successful lifestyle intervention resulting in a significant decrease in BMI, body fat content and improved insulin sensitivity (p < 0.0001 each) no differences in homocysteine concentrations could be achieved. However,in the cross-sectional analysis we found a significant and independent, negative correlation between glomerular filtration rate (GFR) and homocysteine levels (r = -0.37; p < 0.0001). In conclusion, our study did not reveal a significant association between levels of homocysteine and insulin resistance in a population with an increased risk for type 2 diabetes. However, plasma homocysteine levels were related to subtle differences in kidney function at this early stage.
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PMID:Plasma homocysteine concentrations in young individuals at increased risk of type 2 diabetes are associated with subtle differences in glomerular filtration rate but not with insulin resistance. 1686 89

Although type 2 diabetes is often characterized by normal or high bone mineral density (BMD), diabetes is associated with increased risk of fracture. This paradoxical phenomenon in type 2 diabetes may be explained by poorer "bone quality" by detrimental collagen cross-links in bone. Recently, we showed that the alteration of enzymatic and nonenzymatic crosslinking in bone could be important for explaining the variation of fracture susceptibility in diabetes (Osteoporos Int, 2006. Epub ahead of print). In this review, we describe that low turnover bone, hyperglycemia, mildly hyperhomocysteinemia, and vitamin B(6) insufficiency are crucial determinants of detrimental crosslinking of bone collagen in diabetes.
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PMID:[Poor bone quality in diabetes: detrimental collagen cross-link pattern reduces bone strength without change in bone mineral density]. 1688 36

Autoimmune or type 1 diabetes mellitus (T1DM), accounts for 90-95% of all cases of diabetes, while type 2 diabetes mellitus (T2DM), characterized by impaired insulin sensitivity and production, accounts for the other 5-10%. Atherosclerotic process starts during childhood and recognize several mechanisms that are activated in response to NOXIUS STIMULI and participate in a complex state which is accepted to be a chronic inflammatory state. T1DM patients, especially those with a non-optimal metabolic control, have a higher risk of developing all macrovascular complications such as myocardial infarction, stroke and silent ischemia. Macrovascular disease is mainly associated with hyperglycemia, dyslipidemia, obesity, hypertension, hypercoagulable state, cigarette smoking, lack of exercise, endothelial dysfunction, hyperhomocysteinemia and vascular wall abnormalities. In this paper we review the importance of traditional and non-traditional risk factors for macrovascular complications in children with T1DM and discuss their role in the pathogenesis of the excess cardiovascular mortality in these patients.
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PMID:Macroangiopathy in adults and children with diabetes: risk factors (part 2). 1711 Dec 97

The next decade will face an increase in the number of patients affected by end-stage renal disease. In line with the growing incidence of type 2 diabetes, hypertension and old age in the general population, we can expect a dramatic increase of uremic patients needing a substitutive treatment of renal function. On the basis of the current trends, we expect an exponential growth of cardiovascular complications in both dialysis and transplant populations. Progress in the treatment of end-stage renal disease will aim at the prevention of cardiovascular complications, that remain the leading cause of morbidity and mortality in uremic patients. Preventive interventions for cardiovascular complications should focus on traditional risk factors, such as hypertension, dyslipidemia and obesity, diabetes mellitus, smoking, as well as on the non traditional risk factors inherent in the uremic state, such as anemia, hyperphosphoremia, hyperhomocysteinemia, inflammation and malnutrition. Recent and future innovations in peritoneal dialysis solutions include a larger use of icodextrin, a glucose polymer able to enhance ultrafiltration while inducing less glycation and caloric absorption, and perhaps improving blood pressure control. The gene therapy directed to the mesothelial cells should bring about improvements in nutrition, cardiovascular comorbidity, and dialysis adequacy. Patients submitted to increased hemodialysis time or to the implementation of a night or daily hemodialysis program have shown better blood pressure control, cardiovascular stability, tolerability and perhaps reduced mortality. Modifications of dialysis schedules clearly indicate another road to future improvements in renal replacement therapy. In the field of kidney transplantation, much improvement has already been achieved regarding the prevention of acute rejection, and the new therapeutic strategies are aimed at reducing the incidence of the adverse reactions of immunosuppressive drugs, as well as of the chronic allograft nephropathy. Induction of transplantation tolerance remains the most attractive target, which now seems closer than before because many of the mechanisms involved in the tolerance induction have been better elucidated.
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PMID:[Perspectives on treatment of the renal failure]. 1725 35

This study aims to investigate the relationship between the circulating level of homocysteine and body adiposity in Japanese patients with type 2 diabetes mellitus. We measured the body mass index (BMI), waist and hip circumferences, visceral and subcutaneous adiposities, visceral/subcutaneous (V/S) adiposity ratio, and insulin resistance as assessed by the Homeostasis Model Assessment (HOMA) index in patients with hyperhomocysteinemia. The study group consisted of 17 Japanese patients with type 2 diabetes and hyperhomocysteinemia (age: 62+/-10 years, mean+/-S.D.), and the control group consisted of 24 age-matched type 2 diabetes patients with normohomocysteinemia (60+/-11 years). The visceral adiposity, HOMA index, and V/S ratio were significantly higher in the hyperhomocysteinemia group than in the normohomocysteinemia group (P<0.05). In contrast, the BMI, hip circumference, and subcutaneous adiposity were similar between the two groups (P>0.1). Furthermore, multiple regression analysis showed that hyperhomocysteinemia was closely related to insulin resistance and visceral adiposity. Our results indicate that the presence of hyperhomocysteinemia in our population of Japanese patients with type 2 diabetes-associated insulin resistance was associated with increased visceral but not subcutaneous adiposity.
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PMID:Hyperhomocysteinemia is associated with visceral adiposity in Japanese patients with type 2 diabetes mellitus. 1729 21

The purpose of the study was to evaluate the effects of hyperhomocysteinemia (HHC) on vascular-thrombocyte and coagulation hemostasis and the development of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (DM2). DM 2 patients with or without CAD were examined; high incidence of HHC (40.3%) was revealed. The level of homocysteine was significantly higher in DM2 patients with CAD vs. non-CAD subjects. Among patients with DM2 and CAD the level of the amino acid was elevated in 77.1% of cases with a history of myocardial infarction. In patients with DM2, CAD, and HHC, vascular-thrombocyte hemostasis factors were found to be hyperactive, while anticoagulatory ones were suppressed. These changes in the hemostatic system in HHC increase the probability of thrombus formation and CAD progress.
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PMID:[Hyperhomocysteinemia in coronary artery disease and hemostasis disorders in patients with type 2 diabetes mellitus]. 1766

Type 2 diabetes mellitus induces a characteristic platelet hyperactivity that might be due to several factors including oxidative stress and abnormal intracellular Ca2+ homeostasis. Hyperhomocysteinaemia is considered a risk factor in the development of thrombosis although its effect on platelet function and the mechanisms involved are still poorly understood. Here we show that homocysteine (Hcy) induce a concentration-dependent increase in endogenous production of reactive oxygen species (ROS), which was significantly greater in platelets from diabetic patients than in controls. Platelet treatment with Hcy resulted in Ca2+ release from the dense tubular system and the acidic stores. Ca2+ mobilisation-induced by Hcy consisted in two components, an initial slow increase in intracellular free Ca2+ concentration ([Ca2+]i) and a rapid and marked increase in [Ca2+]i, the second leading to the activation of platelet aggregation. As well as ROS generation, Ca2+ mobilization and platelet aggregation were significantly greater in platelets from diabetic donors than in controls, which indicate that platelets from diabetic donors are more sensitive to Hcy. These findings, together with the hyperhomocysteinaemia reported in diabetic patients, strongly suggest that Hcy might be considered a risk factor in the development of cardiovascular complications associated to type 2 diabetes mellitus.
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PMID:Effect of homocysteine on calcium mobilization and platelet function in type 2 diabetes mellitus. 1808 91

Patients with diabetes mellitus are prone to cardiovascular disease, and risk factors presumably unrelated to diabetes, such as hyperhomocysteinemia, may be involved in the atherothrombotic process in these subjects. Plasma homocysteine levels are usually normal in diabetes, although both lower and higher levels have been reported. This has been ascribed to hyperfiltration and renal dysfunction or low folate status, respectively. Insulin resistance does not appear to be a major determinant of plasma homocysteine level. Hyperhomocysteinemia has been associated with microalbuminuria and retinopathy in type 1 and type 2 diabetes. In patients with type 2 diabetes, plasma homocysteine concentration has also been shown to be related to macrovascular disease and death. This relation seems to be stronger in subjects with diabetes than without. The underlying pathophysiological mechanism of this increased vascular risk remains unexplained, but may relate to worsening of endothelial dysfunction or structural vessel properties. Because homocysteine and diabetes have an apparent synergistic detrimental vascular effect, patients with diabetes are good candidates for screening and treatment with folic acid until the results of ongoing clinical trials are available.
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PMID:Epidemiology of homocysteine as a risk factor in diabetes. 1837 Jun 32

Hyperhomocysteinemia is a well-established risk factor for cardiovascular disease. The association of hyperhomocysteinemia with diabetes mellitus is complex and may explain some of the risk of CVD in diabetics not explained by traditional risk factors. Both modifiable and non-modifiable factors interact with homocysteine metabolism and determine the plasma homocysteine concentrations. These include genetic abnormalities, age, sex, and various nutritional and hormonal determinants, all of which play a role in atherosclerosis and accelerated peripheral and cardio-vascular disease (CVD). Several medications modulate homocysteine metabolism and hence may play a role in the pathogenesis of CVD. Changes in renal function and interference with the homocysteine metabolism account for some of these drug effects. While a few of these drugs raise plasma homocysteine concentrations, others are beneficial and may counter some of the deleterious effects of hyperhomocysteinemia. Treatment of hyperhomocysteinemia with vitamins lowers plasma homocysteine concentrations and also reverses many of these drug effects. Little data is available on the effect of this intervention on cardiovascular outcomes. This review briefly outlines the effect of various medications used in the management of type 2 diabetes mellitus and metabolic syndrome.
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PMID:Effect of pharmacological treatments for diabetes on homocysteine. 1837 Jun 36


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