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

Cardiovascular disease (CVD) accounts for almost 50% of all deaths in industrialized nations. As much as 70% of CVD can be prevented or delayed with dietary choices and lifestyle modifications. Western-style diets, sedentary lifestyles, and cigarette smoking are key modifiable CVD risk factors. Although CVD mortality was trending downward for almost 50 years, a resurgence, both nationally and globally, has occurred. A growing epidemic of obesity ("globesity"), decreasing physical activity, and persistent cigarette smoking are major behavioral factors underlying this change. Diet and lifestyle increase CVD risk both directly and indirectly. Direct effects include biological, molecular, and physiologic alterations, including inflammatory stimuli and oxidative stresses. Indirect effects include diabetes, dyslipidemias, and hypertension. However, trials studying links between diet and CVD remain notoriously difficult to execute and interpret. Diet interventions are typically confounded by other aspects of an overall diet as well as by lifestyle. Furthermore, benefits derived from a specific dietary or lifestyle intervention may not be proportional to the degree of risk posed by the unhealthy diet or lifestyle. Nonetheless, therapeutic rationale for diet and lifestyle are supported by basic and clinical research. Key components of a healthy aggregate diet include 1) reduced caloric intake; 2) reduced total fat, saturated fat, trans fat, and cholesterol with proportional increases in monosaturated, n-3 (omega-3), and n-6 fatty acids; 3) increased dietary fiber, fruit, and vegetables; 4) increased micronutrients (eg, folate, B6, B12); 5) increased plant protein in lieu of animal protein; 6) reduced portions of highly processed foods; and 7) adopting a more Mediterranean or "prudent" dietary pattern over the prevailing "western" dietary pattern. Key lifestyle interventions include increased physical activity and smoking cessation. Translation of the benefits of healthy diet and lifestyle to the wider population requires both individual and public health strategies targeting at-risk groups.
 ...
PMID:Cardiovascular disease: optimal approaches to risk factor modification of diet and lifestyle. 1640 83

S-Adenosylhomocysteine (SAH) is the metabolic precursor of all the homocysteine (Hcy) produced in the body. It is formed by the enzyme SAH hydrolase in a reversible reaction. In a previous study we have shown that plasma SAH is a more sensitive indicator of the risk for cardiovascular disease, and in a second study involving patients with renal disease, we also showed that it is a more sensitive indicator of renal insufficiency than plasma Hcy. However, in the latter study, the patients with renal disease were older and had a variety of other diseases such as diabetes and primary hypertension, which are associated with vascular disease and which could reduce renal function by involvement of the kidneys. Our objective was to rule out these complicating factors as the cause of the elevated SAH in renal disease and determine whether renal insufficiency alone was the cause of the elevated SAH. We therefore measured SAH, Hcy, folate, and vitamin B12 in 23 patients between the ages of 1 and 18 years with a wide range of renal function, but who had none of these complicating factors. Glomerular filtration rate (GFR) was calculated using serum creatinine according to the Schwartz formula. None of the children were deficient in folate or vitamin B12. After adjusting for age, folate, and vitamin B12, there was a modest and insignificant decrease of 0.033 micromol/L of Hcy associated with an increase of 1 mL/min of GFR (95% confidence interval, -0.066 to 0.0002). However, there was a strong and statistically significant association between log(SAH) and log(GFR): P < .0005, R2 = 0.76. This result suggests that plasma SAH rather than Hcy is the metabolite primarily affected in renal disease. We suggest that plasma Hcy elevations that have been linked to vascular disease may be due to elevated SAH resulting from renal insufficiency.
 ...
PMID:Relationship between plasma S-adenosylhomocysteine concentration and glomerular filtration rate in children. 1642 34

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease. Insulin seems to be a critical antigen recognized by autoreactive T cells. In this study, we performed T cell epitope mapping of insulin using serial overlapping peptides in Japanese patients with T1D. Serial overlapping insulin peptides comprising 23 peptides, which were each 15-amino acid long, were prepared based on insulin sequence. Cytokine secretion from peripheral T cells against these peptides was studied by enzyme-linked immunospot (ELISPOT) assay in 18 patients with recent-onset T1D and 12 patients with established T1D, and compared with 17 healthy control subjects. In ELISPOT assay, IFN-gamma-secreting T cells, but not IL-4, against several insulin peptides were observed in 77.8% of patients with recent-onset T1D, 50.0% of patients with established T1D, and 0% of healthy control subjects. All epitopes recognized by T cells were identified in the B-chain of insulin. The most frequent epitope existed at the B10-24 region (9/18), followed by B1-15 and B11-25 regions (6/18, each), with B4-18, B9-23, and B12-26 identified in some patients. These data did not correlate with insulin autoantibodies or HLA-DRB1 of the patients. This is the first report of T cell epitope mapping using one amino acid serial overlapping peptides of insulin in T1D. ELISPOT assay revealed the frequent existence of insulin peptide-specific T cells in patients with recent-onset and established T1D. The T cell epitopes of insulin were similar but not identical in our cohort, which probably explains the difficulty encountered in prevention of human T1D by using insulin.
 ...
PMID:T cell epitope mapping study with insulin overlapping peptides using ELISPOT assay in Japanese children and adolescents with type 1 diabetes. 1649 87

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.
 ...
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

Spina bifida, anencephaly, and encephalocele are commonly grouped together and termed neural tube defects (NTD). Failure of closure of the neural tube during development results in anencephaly or spina bifida aperta but encephaloceles are possibly post-closure defects. NTD are associated with a number of other central nervous system (CNS) and non-neural malformations. Racial, geographic and seasonal variations seem to affect their incidence. Etiology of NTD is unknown. Most of the non-syndromic NTD are of multifactorial origin. Recent in vitro and in vivo studies have highlighted the molecular mechanisms of neurulation in vertebrates but the morphologic development of human neural tube is poorly understood. A multisite closure theory, extrapolated directly from mouse experiments highlighted the clinical relevance of closure mechanisms to human NTD. Animal models, such as circle tail, curly tail, loop tail, shrm and numerous knockouts provide some insight into the mechanisms of NTD. Also available in the literature are a plethora of chemically induced preclosure and a few post-closure models of NTD, which highlight the fact that CNS malformations are of hetergeneitic nature. No Mendelian pattern of inheritance has been reported. Association with single gene defects, enhanced recurrence risk among siblings, and a higher frequency in twins than in singletons indicate the presence of a strong genetic contribution to the etiology of NTD. Non-availability of families with a significant number of NTD cases makes research into genetic causation of NTD difficult. Case reports and epidemiologic studies have implicated a number of chemicals, widely differing therapeutic drugs, environmental contaminants, pollutants, infectious agents, and solvents. Maternal hyperthermia, use of valproate by epileptic women during pregnancy, deficiency and excess of certain nutrients and chronic maternal diseases (e.g. diabetes mellitus) are reported to cause a manifold increase in the incidence of NTD. A host of suspected teratogens are also available in the literature. The UK and Hungarian studies showed that periconceptional supplementation of women with folate (FA) reduces significantly both the first occurrence and recurrence of NTD in the offspring. This led to mandatory periconceptional FA supplementation in a number of countries. Encouraged by the results of clinical studies, numerous laboratory investigations focused on the genes involved in the FA, vitamin B12 and homocysteine metabolism during neural tube development. As of today no clinical or experimental study has provided unequivocal evidence for a definitive role for any of these genes in the causation of NTD suggesting that a multitude of genes, growth factors and receptors interact in controlling neural tube development by yet unknown mechanisms. Future studies must address issues of gene-gene, gene-nutrient and gene-environment interactions in the pathogenesis of NTD.
 ...
PMID:Etiology, pathogenesis and prevention of neural tube defects. 1673 63

Although cobalamin (vitamin B12) was isolated almost 60 years ago, its biochemical, physiologic and neurologic effects remain incompletely defined. New observations suggest renal regulation of cobalamin metabolism; actions of cobalamin on nucleic acid and protein function; and a role for cobalamin in cytokine and growth factor regulation. Clinically, no gold standard has emerged for the diagnosis of cobalamin deficiency. Moreover, cobalamin resistance may occur in diabetes, renal insufficiency and advanced age, leading to functional cobalamin deficiency despite adequate cobalamin nutriture. Finally, high-dose cobalamin therapy may have salutary pharmacologic effects on neurologic function in a variety of disorders. Many studies lacked appropriate control groups. However, at this time, therapeutic trials with pharmacologic doses of cobalamin are suggested when findings consistent with cobalamin deficiency are present regardless of the results of diagnostic tests. While oral cobalamin immediate-release is adequate for many patients, its effectiveness in reversing neurologic abnormalities has yet to be established.
 ...
PMID:Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment. 1681 9

This article provides practical advice about foods and dietary supplements that are beneficial for the health of older people. Overweight and obesity are among the most common nutrition-related disorders in older people. A plant-based diet is associated with reduced risk of chronic diseases such as obesity, cardiovascular disease, cancer, and diabetes. Vitamin B12 deficiency is prevalent in older adults, but there are misconceptions about the causes, consequences, and treatments. Diminished synthesis of vitamin D in the skin that occurs with aging and poor dietary intake contribute to the high prevalence of poor vitamin D status in older adults. Vitamin D deficiency is associated with chronic disorders beyond poor bone health. Supplements containing vitamin B12 and vitamin D will help older adults meet their needs for these key nutrients.
 ...
PMID:Nutrition and aging--practical advice for healthy eating. 1684 55

Major risk factors for cardiovascular diseases (myocardial infarction, angina pectoris, brain infarction) are age, male, smoking, high LDL-cholesterol, low HDL-cholesterol, high blood pressure, and diabetes mellitus. In Japanese population at large, healthy life-style to prevent cardiovascular diseases are; quit smoking, walking faster, saturated fat intake ranging 4.5-7 en%, lesser intake of trans fatty acids, cholesterol intake less 750 mg/day (male) and 600 mg/day (female), eat fish everyday, eat more folic acid, B6, and B12, eat grain, eat soybean products. However, it is not known whether this recommendation is also applied to NIDDM to prevent cardiovascular diseases. Based on reported evidences, to prevent cardiovascular diseases, NIDDM should quit smoking, eat fish everyday, and increase physical activity.
 ...
PMID:[Lifestyle to prevent cardiovascular disease in NIDDM]. 1708

The amino acid homocysteine (Hcy), formed from methionine has profound importance in health and diseases. In normal circumstances, it is converted to cysteine and partly remethylated to methionine with the help of vit B12 and folate. However, when normal metabolism is disturbed, due to deficiency of cystathionine-beta-synthase, which requires vit B6 for activation, Hcy is accumulated in the blood with an increase of methionine, resulting into mental retardation (homocystinuria type I). A decrease of cysteine may cause eye diseases, due to decrease in the synthesis of glutathione (antioxidant). In homocystinurias type II, III and IV, there is accumulation of Hcy, but a decrease of methionine, thus, there is no mental retardation. Homocysteinemia is found in Marfan syndrome, some cases of type I diabetes and is also linked to smoking and has genetic basis too. In hyperhomocysteinemias (HHcys), clinical manifestations are mental retardation and seizures (type I only), ectopia lentis, secondary glaucoma, optic atrophy, retinal detachment, skeletal abnormalities, osteoporosis, vascular changes, neurological dysfunction and psychiatric symptoms. Thrombotic and cardiovascular diseases may also be encountered. The harmful effects of homocysteinemias are due to (i) production of oxidants (reactive oxygen species) generated during oxidation of Hcy to homocystine and disulphides in the blood. These could oxidize membrane lipids and proteins. (ii) Hcy can react with proteins with their thiols and form disulphides (thiolation), (iii) it can also be converted to highly reactive thiolactone which could react with the proteins forming -NH-CO- adducts, thus affecting the body proteins and enzymes. Homocystinuria type I is very rare (1 in 12 lakhs only) and is treated with supplementation of vit B6 and cystine. Others are more common and are treated with folate, vit B12 and in selected cases as in methionine synthase deficiency, methionine, avoiding excess. In this review, the role of elevated Hcy levels in cardiovascular, ocular, neurologial and other diseases and the possible therapeutic measures, in addition to the molecular mechanisms involved in deleterious manifestations of homocysteinemia, have been discussed.
 ...
PMID:Biochemistry of homocysteine in health and diseases. 1713 33

In recent years, the recourse to obesity surgery to treat morbid obesities has grown. The number of "malabsorptive" interventions, such as the gastric bypass (RYGB: Roux-en-Y gastric bypass) increases each year. The RYGB, which combines two mechanisms promoting weight loss, restriction and malabsorption, has proven its effectiveness in term of weight loss and improvement of obesity-associated co-morbidities. However this intervention involves a profound change in digestive physiology and is the source of nutritional and metabolic complications. The deficits observed most frequently concern proteins, iron, calcium, vitamin B12 and vitamin D. The deficiencies in vitamin B1 are rare but potentially serious. Multidisciplinary follow-up is essential to ensure prevention, diagnosis and treatment of these complications. Based on an analysis of the literature, this article summarizes the various nutritional complications observed after RYGB and the means to diagnose it. It proposes practical recommendations for follow-up, preventive supplementation and treatment of these deficiencies, both generally and in the more specific case of a pregnancy after RYGB.
Diabetes Metab 2007 Feb
PMID:Nutritional deficiency after gastric bypass: diagnosis, prevention and treatment. 1725 28


<< Previous 1 2 3 4 5 6 7 8 9 10