Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to determine the possibility of assessing intrauterine fetal well being by measuring amniotic fluid steroid levels, a number of selected glucocorticoids and estrogens were assayed. Estriol (E3) and estetrol (E4) levels at 36-40 weeks of pregnancy, especially that of total E3 (T-E3 and unconjugated E4 (U-E4) rose significantly (p less than 0.01), and were at a ratio of T-E3/U-E3 8; T-E4/U-E4 2, respectively. A definite correlation was found between T-E3 and U-E3 (r = 0.97) which was not detected in the case of E4, and there was a high correlation with umbilical arterial levels of both unconjugated and total E3 and E4. Amniotic fluid cortisol (F) levels in both unconjugated (U-F) and sulfate conjugated (S-F) rose preferentially at 36-40 weeks and exceeded the levels of both umbilical arterial and maternal peripheral plasma (p less than 0.01). Both tetrahydro-cortisone (THE) and -cortisol (THF) levels increased at 29-35 weeks which in the select cases were comparable with the increases seen at 36-40 weeks. The THE level showed a definite correlation with that of umbilical artery (r = 0.73) whereas this was not the case for S-F. In pregnancies complicated with toxemia and/or diabetes mellitus, T-E3 and S-F levels are less than the lower limits for normal pregnancies. This tendency was not observed with T-E4 and THE. In pregnancies with severe RH isoimmunization, the levels of T-E3, T-E4 and S-F are markedly lower than those seen in normal pregnancies, and do not display the increase with gestational advances. On the other hand, THE and THF levels were shown to be at levels higher than in normal pregnancies. Thus, in the latter half of pregnancy, amniotic fluid steroid assays, especially T-E3, S-F and THE may be of use in the assessment of fetal well being.
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PMID:[Amniotic fluid cortisol, tetrahydrocortisone, estriol and estetrol in normal and high risk pregnancy (author's transl)]. 727 51

Mild hyperhomocysteinemia has been identified as a risk factor for arterial disease and for venous thrombosis. Individuals homozygous for the thermolabile variant of the methylene tetrahydrofolate reductase gene (MTHFR) which results from a common mutation Ala677-->Val and is found in 5-15% of the general population, have significantly elevated plasma homocysteine levels and may account for one of the genetic risk factors in vascular disease. We have analyzed the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous thrombosis. We studied 191 patients with arterial disease and 127 individuals with venous thrombosis and compared with 296 unmatched controls. The results showed that there was a high prevalence of homozygotes for the mutated MTHFR-T allele among a group of patients with arterial disease (19%) in the absence of hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to controls (4%), odds ratio of 5.52 (95% C.I., 2.27 to 13.51). The prevalence of homozygotes among patients with venous thrombosis was 11%, odds ratio of 2l93 (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio of 2.63, even after we excluded 27 patients with hereditary thrombophilia (e.g. factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S, antithrombin III, or factor XII) from the 127 overall cases with venous thrombosis. These data support the hypothesis that being a homozygote for the MTHFR-T is a risk factor for the development of arterial disease and also for venous thrombosis.
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PMID:The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. 918 84

The increasing prevalence of traditional atherosclerotic risk factors have been documented in Asia but the real impact on prevalence of coronary heart disease (CHD) remains unclear. Smoking, hypertension, hypercholesterolaemia, diabetes mellitus and obesity are present in only 50% of CHD. In community studies of Chinese in Hong Kong and southern mainland-China, aging, smoking and hypercholesterolaemia were found to have a less impact on endothelial function in the Chinese compared with Caucasians in London and Sydney. As endothelial dysfunction is an early event in atherogenesis, there will be a strong need to search for newer risk factors for CHD in Asia, which may become more important in many Asian countries now in the process of modernization. Recently, heterozygous hyperhomocysteinaemia (with or without folate deficiency) was found to be an independent risk factor for arterial endothelial dysfunction, and hyperhomocysteinaemia in association with smoking was a significant risk factor for premature coronary heart disease in Hong Kong Chinese. Other newer factors which have emerged include folate deficiency, low HDL-cholesterol, insulin resistance, abdominal obesity, Methylene-tetrahydrofolate Reductase and Angiotensin Converting Enzyme gene polymorphism.
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PMID:New risk factors for coronary heart disease in Asia. 946 82

The effects of hypercortisolemia and ACTH on the metabolism of cortisol in congenital adrenal hyperplasia, Cushing's syndrome, and exogenous ACTH and cortisol administration were investigated by analysis of the respective urinary tetrahydro-metabolites of cortisol (THF and aTHF) and cortisone (THE) by capillary gas chromatography. The results for the patients with congenital adrenal hyperplasia establish that ACTH hypersecretion in the absence of an associated marked elevation of plasma cortisol does not cause inhibition of the 11beta-OHSD enzyme. In contrast elevated plasma cortisol levels (adrenal adenoma or intravenous cortisol administration) in the presence of suppressed ACTH secretion leads to significant inhibition of the peripheral conversion of cortisol to cortisone. The latter results are equivalent to the mode of cortisol metabolism noted during clinical states of ACTH hypersecretion and hypercortisolemia (Cushing's disease, ectopic ACTH syndrome and ACTH administration). The overall findings provide convincing evidence that ACTH hypersecretion is not associated with specific in vivo inhibition of 11beta-OHSD enzyme activity.
Exp Clin Endocrinol Diabetes 1998
PMID:Effect of hypercortisolism and ACTH on the metabolism of cortisol. 951 61

We assessed the contribution of the serum homocysteine (Hcy) level, an independent risk factor for vascular disease, and methylene tetrahydrofolate reductase (MTHFR) gene polymorphism to the variability of intimal-medial thickness (IMT) of the common carotid artery in middle-aged non-insulin-dependent diabetes mellitus (NIDDM) subjects. One hundred thirty NIDDM patients (60 males and 70 females) with a mean age of 53 +/- 10 years and a mean diabetes duration of 11.3 +/- 7.9 years were enrolled for the study. Exclusion criteria included liver, heart, kidney, or other major-organ disease. Fasting total serum Hcy, folate, and vitamin B12 and clinical chemistry analyte levels were measured. MTHFR polymorphism was determined by polymerase chain reaction (PCR). IMT and plaques or stenosis in the common carotid were measured by ultrasonography. Serum Hcy was inversely correlated with vitamin levels and was slightly higher in subjects with the Val/Val genotype versus Ala/Val and Ala/Ala (P = .02); no differences in genotype were found in subjects with folate or vitamin B12 at or above the median level. In univariate analysis, common carotid IMT was significantly associated with age (P = .00001), the body mass index ([BMI] P = .0003), uric acid (P = .004), systolic blood pressure (P = .03), glycemia (P = .03), and total cholesterol (P = .04). No significant association was found between serum Hcy or MTHFR polymorphism and IMT. In multiple regression analysis, age (P = .0001), uric acid (P = .03), glycemia, and the BMI (P = .05) were independently associated with IMT and explained about 42% of IMT variability. In 130 NIDDM patients without nephropathy, basal levels of serum Hcy, as well as MTHFR polymorphism, did not predict significant changes in common carotid IMT.
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PMID:Lack of association between carotid intima-media thickness and methylenetetrahydrofolate reductase gene polymorphism or serum homocysteine in non-insulin-dependent diabetes mellitus. 1087 95

Hyperhomocysteinemia is a well established risk factor for cardiovascular disease, and multiple factors likely lead to abnormal regulation of plasma homocysteine in patients with diabetes. To examine a possible role for insulin and glucose in homocysteine metabolism, we examined the activity of two important enzymes of homocysteine metabolism in hepatocytes. In various tissues of six mice, methylene tetrahydrofolate reductase (MTHFR) activity was present in all tissues tested and the highest concentration (per gram) was in the brain. In contrast, cystathionine beta-synthase (CBS) activity appeared to be present only in the liver and to a small extent in the kidney. Using HEP G2 cells in culture, MTHFR activity was 3.3+/-0.8 nmol/h when the glucose concentration in the medium was 100 mg/dl and fell to 2.3+/-0.3 nmol/h when glucose was increased to 300 mg/dl. MTHFR activity was 3.4+/-0.3 nmol/h when cells were exposed to an insulin concentration of 5 mU/ml and fell to 2.8+/-0.3 nmol/h when insulin concentration was increased to 200 mU/ml (P<0.01). In contrast CBS activity increased from 0.017 to 0.13 U/ml by increasing the glucose concentration in the medium (P<0.01), but decreased from 0.04 to 0.02 (P<0.01) when the insulin concentration was increased from 5 to 200 mU/ml, respectively. We conclude that CBS and MTHFR have different tissue distributions, with CBS being present predominantly in liver and kidney, and MTHFR found in many tissues. In addition, both insulin and glucose affect the activity of the two enzymes when added to hepatocytes in vitro. If such effects occur in humans with hyperglycemia and hyperinsulinemia, then alterations in homocysteine metabolism may contribute to the accelerated macrovascular disease associated with insulin resistance or type 2 diabetes.
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PMID:The effect of glucose and insulin on the activity of methylene tetrahydrofolate reductase and cystathionine-beta-synthase: studies in hepatocytes. 1158 7

Epidemiological studies of human populations show that poor growth in utero predisposes an individual to the later development of type 2 (non-insulin-dependent) diabetes mellitus and hypertension in adulthood. This phenomenon is not confined to man; feeding pregnant rats diets moderately deficient in protein has a similar effect, programming the adult blood pressure and glucose metabolism of the offspring. A restriction in the amino acid supply was thought to cause poor fetal growth. However, recent experiments have shown that this is not the case and instead have implicated the metabolism of the S-containing amino acids. Many semi-synthetic experimental diets contain an imbalance in S-containing amino acids, forcing the animal to synthesise a sizeable part of its cysteine requirement from methionine. Unfortunately, when the diet is low in protein, the oxidation of amino acids is reduced, perturbing methionine metabolism and increasing levels of homocysteine. It is this interaction between protein content and composition of the diet which influences neonatal viability and may also determine the long-term health of the offspring. An excess of homocysteine is known to affect levels of two of the main mediators of cellular methylation reactions, S-adenosyl methionine and methylene tetrahydrofolate. S-adenosyl methionine is the methyl donor for the methylation of newly-synthesised DNA, regulating chromatin assembly and gene expression. The balance between S-adenosyl methionine and the methylated derivatives of folic acid may be critical for the development of differentiating cells and the long-term regulation of gene expression.
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PMID:Manipulating the sulfur amino acid content of the early diet and its implications for long-term health. 1200 97

A moderate increase of total homocysteine (tHcy) plasma levels seems to increase cardiovascular disease (CVD) risk in Type 2 diabetic subjects, but its relationship with diabetes and insulin-resistance is still controversial. We examined whether mild hyperhomocysteinemia and its major genetic determinant would cluster with the metabolic syndrome (MS) in Type 2 diabetes. One hundred Type 2 diabetic subjects with and without MS were enrolled in the study. Fasting tHcy, vitamin B12, and folate plasma levels, insulin-resistance [assessed by homeostasis model assessment, (HOMAIR)] and the methylene tetrahydrofolate reductase (MTHFR) C677T genotype were assessed in all the participants. Geometric mean tHcy concentration and the prevalence of mild hyperhomocysteinemia, as commonly defined by tHcy >/=15 micromol/l, were comparable in diabetic subjects with and without MS, even after adjustment for age, sex, vitamin B12, folate and creatinine levels. In both groups, the MTHFR C677T genotype distribution was not significantly different from the Hardy-Weinberg equilibrium, with a TT homozygous frequency of 21% in subjects with and 18% in those without the syndrome (p=ns). tHcy plasma levels and the degree of insulin-resistance did not differ across MTHFR genotypes in both groups, even after multivariable adjustment. Overall, tHcy significantly correlated with creatinine (r=0.25; p=0.009) and trygliceride concentrations (r=0.24; p=0.02), but not with HOMAIR. At multivariate analysis, only creatinine was significantly correlated with tHcy levels (beta=0.42; p=0.001). In conclusion, hyperhomocysteinemia and the common C677T variant of MTHFR gene are not associated with MS in Type 2 diabetic subjects.
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PMID:Mild hyperhomocysteinemia and the common C677T polymorphism of methylene tetrahydrofolate reductase gene are not associated with the metabolic syndrome in Type 2 diabetes. 1668 31

Polycystic ovary syndrome (PCOS) is a heterogeneous condition with unknown etiology and is considered to be the most common endocrine disorder in women of reproductive age. Two meta-analyses are presented here concerning the association of Plasminogen Activator Inhibitor 1 (PAI-1) 4G/5G polymorphism and the methylene-tetrahydrofolate reductase (MTHFR) C677T polymorphism with the risk of developing PCOS. Seven studies were included concerning PAI-1 (1538 cases, 710 controls) and six studies concerning MTHFR C677T (223 cases, 392 controls). Overall, a significant association was found for PAI-1, with the odds ratio (OR) for 4G carriers versus 5G homozygotes being equal to 1.600 (95% CI 1.052, 2.434) with strong evidence for dominant inheritance. There was however a large between-studies variability (I(2) = 67.3%). No evidence was found for association of MTHFR C677T polymorphism with PCOS (OR for the TT+CT versus CC comparison equal to 0.940 with 95% CI 0.561, 1.575). No evidence of publication bias was found in these meta-analyses. PAI-1 4G/5G polymorphism seems to be associated with the risk of developing PCOS. Further studies are needed in order to investigate the etiologic mechanism behind this association, as well as the interrelations with other components of the metabolic syndrome (hypertension, diabetes, etc.).
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PMID:Plasminogen activator inhibitor-1 4G/5G and 5,10-methylene-tetrahydrofolate reductase C677T polymorphisms in polycystic ovary syndrome. 2270 71

Metabolic syndrome (MetS) are consist of central obesity, diabetes, dyslipidemia and hypertension. Previous studies have reported possible association of migraine and MetS were reviewed. Migraine is a prevalent disabling disorder and have been regarded as an episodic and functional disorder. However, recent evidence suggests that in some cases, the disease may follow a chronic and progressive course. On the basis of available evidence, obesity is considered to be associated with migraine frequency and progression. The association between diabetes and migraine is unclear. Similarly, association of migraine with hypertension is also unclear. Female migraineurs commonly have an unfavorable cholesterol profile, i.e. one with high total cholesterol and low HDL levels. Obesity can be considered as a proinflammatory state in which increased inflammatory mediators, vascular hyperreactivity, plasma calcitonin gene-related peptide (CGRP) concentrations and decreased adiponectin concentrations are observed. These alterations can cause an increase in the frequency of migraine attacks developed of central sensitization, and thereafter, chronic migraine. Migraine and obesity may share some neurobiological abnormalities. Orexins modulate both pain and metabolism. Dysfunction in the orexin pathways seems to be a risk factor for both conditions. The methylene-tetrahydrofolate reductase (MTHFR) gene and the angiotensin converting enzyme (ACE) gene exhibit polymorphism. C677Tmutation in the MTHFR gene and the D-allele of the ACE gene are the shared risk factors for the development of migraine and cardiovascular disease. Certain beta-blockers, Ca blockers, ACE inhibitors, and angionten II receptor blocker (ARB) have excellent efficacy in migraine prophylaxis. The pharmacological mechanism of these agents do not seem to stand on their antihypertensive effect, but the other mechanism of action. Appropriate meal, sleep, and exercise are important for the management of MetS and migraine headaches.
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PMID:[Metabolic syndrome and prevention of migraine headache]. 1988 41


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