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

Morbidity and mortality from diabetes mellitus remain high despite managing the traditional risk factors. Recent data imply that the pathophysiology of macrovascular and microvascular complications involve other factors. The metabolic syndrome precedes the onset of type 2 diabetes by many years. Early treatment of individuals with this syndrome might delay the onset of diabetes and its complications. Endothelial dysfunction, subclinical inflammation and impaired fibrinolysis may contribute to progression of macrovascular as well as microvascular complications. The roles of infection and hyperhomocysteinemia are less clear but may be significant. This review discusses the current knowledge on these "non-traditional" risk factors and therapies to improve them.
 ...
PMID:Novel cardiovascular risk factors and macrovascular and microvascular complications of diabetes. 1286 62

Homocysteine has emerged as a novel independent marker of risk for the development of cardiovascular disease over the past three decades. Additionally, there is a graded mortality risk associated with an elevated fasting plasma total homocysteine (tHcy). Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) are now considered to be a strong coronary heart disease (CHD) risk enhancer and a CHD risk equivalent respectively. Hyperhomocysteinemia (HHcy) in patients with MS and T2DM would be expected to share a similar prevalence to the general population of five to seven percent and of even greater importance is: Declining glomerular filtration and overt diabetic nephropathy is a major determinant of tHcy elevation in MS and T2DM. There are multiple metabolic toxicities resulting in an excess of reactive oxygen species associated with MS, T2DM, and the accelerated atherosclerosis (atheroscleropathy). HHcy is associated with an increased risk of cardiovascular disease, and its individual role and how it interacts with the other multiple toxicities are presented.The water-soluble B vitamins (especially folate and cobalamin-vitamin B12) have been shown to lower HHcy. The absence of the cystathionine beta synthase enzyme in human vascular cells contributes to the importance of a dual role of folic acid in lowering tHcy through remethylation, as well as, its action of being an electron and hydrogen donor to the essential cofactor tetrahydrobiopterin. This folate shuttle facilitates the important recoupling of the uncoupled endothelial nitric oxide synthase enzyme reaction and may restore the synthesis of the omnipotent endothelial nitric oxide to the vasculature.
 ...
PMID:Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: the pleiotropic effects of folate supplementation. 1513 82

Hyperhomocysteinemia is thought to have an important role in the pathogenesis of ischemic cerebral infarction. When associated with diabetes mellitus, it might worsen the neurologic course. The aim of the study was to clarify the relation between plasma homocysteine (Hcy) concentrations and silent brain infarction (SBI) in patients with type 2 diabetes mellitus. Total plasma Hcy levels were prospectively studied in 46 patients with type 2 diabetes and SBI (group I), mean age 56+/-5.4 years, as compared to 38 diabetic patients without SBI (group II) and with 31 controls (group III). Homocysteine concentrations were determined using a high-performance liquid chromatography assay. The results were compared using the Student's t test. The mean level of Hcy was 22.6+/-2.4 micromol/l in group I, 19.7+/-1.6 micromol/l in group II and 11.4+/-1.4 micromol/l in group III; between group I and group II p < or = 0.001. These data are consistent with increased Hcy levels in type 2 diabetic patients, contributing to the onset of SBI in some patients. The phenomenon should be considered in any future strategy for the therapy of hyperhomocyst(e)inemia (HHcy).
 ...
PMID:Study of total homocyst(e)ine levels in type 2 diabetic patients with silent brain infarction. 1552 24

Hyperhomocysteinemia is an independent risk factor for atherosclerotic disease. Because serum markers of inflammation and the metabolic syndrome are also associated with atherosclerotic disease and insulin resistance, we investigated whether plasma homocysteine (Hcy) levels were associated with serum markers of inflammation and factors of metabolic syndrome in 223 elderly patients with type 2 diabetes mellitus. The levels of plasma Hcy and serum interleukin-6 (IL-6), high-sensitivity C-reactive protein, and C-peptide were measured. The C677T mutation of methylenetetrahydrofolate reductase (MTHFR) gene was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The number of abnormal metabolic factors (presence of diabetes, blood pressure > or =130/85 mm Hg, triglycerides > or =150 mg/dL, high-density lipoprotein cholesterol <35 mg/dL (men) or <39 mg/dL (women), or body mass index >25 kg/m 2 ) was assessed. Elevated plasma Hcy levels correlated significantly with serum IL-6 ( r = 0.25, P < .001), C-peptide ( r = 0.22, P < .01), and the number of abnormal metabolic factors ( r = 0.20, P < .01), but not with C-reactive protein. Multiple linear regression analysis revealed that log-transformed IL-6, serum C-peptide, vitamin B12 , and creatinine were significant determinants of plasma Hcy levels. The correlation between Hcy and IL-6 levels was strongest in those with TT genotype of C677T MTHFR among 3 genotypes. The association between plasma Hcy and serum IL-6 levels supports the hypothesis that the activation of innate immunity is involved in the pathogenesis of arteriosclerosis in patients with diabetes mellitus who are homozygous for the TT genotype of C677T MTHFR.
 ...
PMID:Association of plasma homocysteine with serum interleukin-6 and C-peptide levels in patients with type 2 diabetes. 1593 19

Hyperhomocysteinemia has been identified as independent risk factor for early atherosclerotic vascular disease. The purpose of our study was to investigate the plasma homocystein (Hcy) concentrations and its relationship with lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx; nitrite plus nitrate) concentrations in age-matched non-obese (n=55) and obese (n=60) female subjects with type 2 diabetes mellitus. Non-obese diabetic patients have significantly higher plasma tHcy and TBARS (p<0.001 and p<0.001), and significantly lower NOx concentrations than the controls (n=25) (p<0.001). The plasma tHcy and TBARS concentrations were higher and nitric oxide concentrations were lower in obese diabetics than in non-obese diabetics (for each comparison; p<0.001). Correlation analysis demonstrated that there was a significant positive correlation between tHcy and TBARS (r=0.452, p<0.01) in diabetics groups. There was no significant correlation between tHcy and plasma NOx, insulin and blood pressure. We thought that Hcy might have a permissive role on the endothelium damage through free radical generating systems and the presence of obesity the free radical induced-damage has been elevated in diabetic patients.
 ...
PMID:Plasma total homocysteine concentrations in obese and non-obese female patients with type 2 diabetes mellitus; its relations with plasma oxidative stress and nitric oxide levels. 1603 31

Although hyperhomocysteinemia, an independent cardiovascular risk factor, is common in type 2 diabetes with nephropathy, the mechanism(s) of this alteration is not known. In healthy humans, hyperinsulinemia increases methionine transmethylation, homocysteine transsulfuration, and clearance. No such data exist in type 2 diabetes either in the fasting state or in response to hyperinsulinemia. To this purpose, seven male type 2 diabetic patients with albuminuria (1.2 +/- 0.4 g/day, three with mild to moderate renal insufficiency) and seven matched control subjects were infused for 6 h with L-[methyl-(2)H(3), 1-(13)C]methionine. Methionine flux, transmethylation, and disposal into proteins as well as homocysteine remethylation, transsulfuration, and clearance were determined before and after euglycemic hyperinsulinemia (approximately 1,000 pmol/l). In type 2 diabetic subjects, homocysteine concentration was twofold greater (P < 0.01) and methionine transmethylation and homocysteine clearance lower (from approximately 15 to >50% and from approximately 40 to >100%, respectively; P < 0.05) than in control subjects. The insulin-induced increments of methionine transmethylation, homocysteine transsulfuration, and clearance were markedly reduced in type 2 diabetic subjects (by more than threefold, P < 0.05 or less vs. control subjects). In contrast, methionine methyl and carbon flux were not increased in the patients. In conclusion, pathways of homocysteine disposal are impaired in type 2 diabetes with nephropathy, both in postabsorptive and insulin-stimulated states, possibly accounting for the hyperhomocysteinemia of this condition.
 ...
PMID:Effects of insulin on methionine and homocysteine kinetics in type 2 diabetes with nephropathy. 1618

Cardiovascular disease is a major problem in diabetes, and risk factors presumably unrelated to diabetes, such as hyperhomocysteinaemia, may be related to the development of cardiovascular complications in diabetic individuals. Plasma homocysteine levels are usually normal in diabetes, although both lower and higher levels have been reported. Homocysteine levels in diabetes are modulated by hyperfiltration and renal dysfunction, as well as low folate status. Insulin resistance does not appear to be a major determinant of plasma homocysteine level. Hyperhomocysteinaemia has been associated with microalbuminuria and retinopathy in type 1 and type 2 diabetes. In patients with type 2 diabetes, plasma homocysteine concentration is a significant predictor of cardiovascular events 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 be related to worsening of endothelial dysfunction and/or structural vessel properties induced by oxidative stress. Because homocysteine and diabetes have apparent synergistic detrimental vascular effects, patients with diabetes are candidates for screening and treatment with folic acid until the results of ongoing clinical trials are available.
 ...
PMID:Homocysteine and vascular disease in diabetes: a double hit? 1619 87

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 diabetics than in subjects without diabetes. 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 negative vascular effect, patients with diabetes are good candidates for screening and treatment with folic acid until the results of ongoing clinical trials are available.
 ...
PMID:Diabetes mellitus and hyperhomocysteinemia. 1622 99

Mild hyperhomocysteinemia is a risk factor for many diseases, including cardiovascular disease. We determined the effects of insulin resistance and of type 2 diabetes on homocysteine (Hcy) metabolism using Zucker diabetic fatty rats (ZDF/Gmi fa/fa and ZDF/Gmi fa/?). Plasma total Hcy was reduced in ZDF fa/fa rats by 24% in the pre-diabetic insulin-resistant stage, while in the frank diabetic stage there was a 59% reduction. Hepatic activities of several enzymes that play a role in the removal of Hcy:cystathionine beta-synthase (CBS), cystathionine gamma-lyase, and betaine:Hcy methyltransferase (BHMT) were increased as was methionine adenosyltransferase. CBS and BHMT mRNA levels and the hepatic level of S-adenosylmethionine were also increased in the ZDF fa/fa rats. Studies with primary hepatocytes showed that Hcy export and the transsulfuration flux in cells from ZDF fa/fa rats were particularly sensitive to betaine. Interestingly, liver betaine concentration was found to be significantly lower in the ZDf fa/fa rats at both 5 and 11 weeks. These results emphasize the importance of betaine metabolism in determining plasma Hcy levels in type 2 diabetes.
 ...
PMID:Homocysteine metabolism in ZDF (type 2) diabetic rats. 1624 51

Point mutations in methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia were implicated in the pathogenesis of diabetic nephropathy (DN) in many ethnic groups. This study addressed the association of C677T and A1298C single nucleotide polymorphisms (SNPs) of MTHFR gene with DN in Tunisian type 2 diabetes (T2DM) patients. Study subjects comprised 93 DN patients, 267 patients with normoalbuminuria, and 400 control subjects. C677T and A1298C genotypes were determined by PCR-RFLP analysis, and homocysteine levels were measured by ELISA. A1298C and C677T were highly prevalent among T2DM patients, with allele frequencies of 0.26 and 0.36, respectively. Higher mutant 677T allele and 677C/T and 677T/T genotypes of C677T SNP, but not A1298C SNP, together with 677C/1298A, 677C/1298C, and 677T/1298A haplotypes were seen in DN patients compared to normoalbuminuric patients, (p<0.001). Plasma homocysteine was positively associated with MTHFR 677T/T genotype among the three groups, and was significantly elevated in double heterozygous DN patients but not in normoalbuminuric patients or controls. Logistic regression analysis with DN as dependent variable showed that homocysteine (OR, 1.153) and MTHFR 677T/T (OR, 9.799) were the only variables associated with DN, after adjusting for possible confounding variables. C677T, but not A1298C, SNP, is a risk factor for DN, presumably acting by elevating homocysteine levels.
 ...
PMID:MTHFR C677T and A1298C gene polymorphisms and hyperhomocysteinemia as risk factors of diabetic nephropathy in type 2 diabetes patients. 1682 93


<< Previous 1 2 3 4 5 6 Next >>