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)

CYP1A1, is one of the key detoxifying enzymes catabolizing cigarette smoking derived toxins and may be relevant to smoking-induced atherogenesis. Recently a CYP1A1 MspI polymorphism at the 3'-flanking region of the gene has been found to be associated with smoking related cancer risk and may, therefore, also be associated with vascular disease. To explore this, we investigated interactive effects between smoking and the CYP1A1 MspI polymorphism on coronary artery disease (CAD), diabetes and hypertension in 701 patients (aged < or =65 years) consecutively referred to Eastern Heart Clinic for angiographic investigation. The frequencies of the TT (80.2%), TC (17.7%) and CC (2.1%) genotypes were in Hardy-Weinberg equilibrium with the rare C allele frequency 0.11. The C allele carriers had an increased risk for triple vessel disease (three major epicardial coronary arteries with > or =50% luminal obstruction, OR, 3.44; 95%CI, 1.46-8.09; P=0.0046) in light smokers (< or =20 packyears). We further identified an interactive effect between smoking, the CYP1A1 MspI polymorphism and type 2 diabetes (chi(2)=9.508, P=0.002). The C allele carriers who were smokers had an increased risk of diabetes (OR, 2.44; 95%CI, 1.32-4.49; P=0.0059). Our study suggests that CYP1A1 may participate in the pathogenesis of atherosclerosis and in the development of diabetes and its vascular complications. The presence of the rare C allele of the CYP1A1 gene in smokers may enhance predisposition to severe CAD and type 2 diabetes. These findings contribute to the understanding of cardiovascular risk and to smoking related vascular disease.
 ...
PMID:Effect of CYP1A1 MspI polymorphism on cigarette smoking related coronary artery disease and diabetes. 1199 59

The high incidence of obesity in Ireland is of growing concern. The Irish Universities Nutrition Alliance North/South Food Consumption Survey found that 18 % of the population are obese and 39% overweight. Obesity and overweight increase the risk of developing CHD, type 2 diabetes, hypertension and some forms of cancer. It is well accepted that the best treatment for obesity is a combination of energy intake reduction and regular exercise. Previously, dietary compliance has been shown to improve when monitored on a regular basis. The lengthy delay between clinic visits to the dietitian has been reported by those who failed to lose weight to be the main reason for poor compliance. A weight monitoring clinic was designed to offer those requiring regular support and encouragement the opportunity to monitor their weights on a more regular basis, while waiting for their return visit to the dietitian in the Outpatient Departments. As resources were limited, an efficient use of time was essential. The clinic design was: 1 h/week; eight to fourteen appointments per clinic; weekly or fortnightly visit; return patients only. The clinic was started on a trial basis in June 1999, and was evaluated in December 2000. Referrals were only taken from other dietitians, and each participant was informed in advance of the necessity of having a return Outpatient Department appointment for full dietary review. Forty-eight participants attended more than three times up to and including December 2000 (seven males, forty-one females). The number of clinic visits ranged from three to twenty-eight. Mean weight at start of clinic was 92.94 kg. Of the group attending, 67 % (thirty-two) successfully lost weight and maintained this weight loss. This ranged from 0.1 kg to 23.5 kg. While in total 31% (fifteen) of attendees had gained weight at December 2000, all attendees, including this fifteen, had lost weight at some point during the clinic. Self-reported reasons given for weight regain included: (1) non-attendance at weight clinic (40%); (2) Christmas or holidays (13%); (3) stress related to family, work (13%); (4) ill-health or medication (13%). The remaining 20% reported no reason. Other findings included better compliance with diet and improved overall balance. There was an overall improvement in other dietary-related problems, e.g. reduced cholesterol, improved glycaemic control, reduced blood pressure. The participants attending the clinic reported decreased clothes size and improved self-image and confidence. They were more enthusiastic about dietary compliance, and all attendees expressed their satisfaction with the clinic and the service.
 ...
PMID:An obesity clinic model. 1200

Patients with type 2 diabetes (DM) demonstrate inadequate insulin release, elevated gluconeogenesis, and diminished nonoxidative glucose disposal. Similar metabolic changes occur during systemic injury caused by infection, trauma, or cancer. Described here are metabolic changes occurring in 16 DM and 11 lung cancer patients (CA) and 13 normal volunteers (NV). After a 10-h overnight fast, all subjects had fasting hormone and substrate concentrations determined, along with rates of glucose production, leucine appearance (LA), and leucine oxidation (LO). Fasting insulin (data not shown) and C-peptide concentrations were elevated in DM and CA compared with weight-matched NV (0.72 +/- 0.09 and 0.64 +/- 0.08 vs. 0.51 +/- 0.03 mg/l, P < 0.05). C-reactive protein concentration was elevated in CA compared with DM and NV (23.3 +/- 6.0 vs. 4.2 +/- 1.4 and 2.1 +/- 0.5 mg/l, P < 0.01). All counterregulatory hormones were normal except for serum cortisol (11.4 +/- 1.0 and 12.1 +/- 1.0 vs. 8.9 +/- 0.7 microg/dl, DM and CA vs. NL, respectively, P < 0.05). Glucose production was increased in DM and CA compared with NV (4.22 +/- 0.6 and 3.53 +/- 0.3 vs. 2.76 +/- 0.2 mg x kg lean body wt(-1) x min(-1), P < 0.01). LO and LA were increased in DM and CA compared with NV (LO: 27.3 +/- 1.5 and 19.7 +/- 1.5 vs. 12.5 +/- 1.1 mmol x kg lean body wt(-1) x min(-1), P < 0.05; LA: 91.9 +/- 6.6 and 90.7 +/- 7.0 vs. 79.1 +/- 6.0 mmol. kg lean body wt(-1) x min(-1), P < 0.01). DM share similar metabolic derangements with CA. The increase in LA may be secondary to an increased glucose production where amino acids are mobilized to provide the liver with adequate substrate to make glucose. The increase in glucose production may also be part of the injury response, or it may represent a form of insulin resistance that exists in both the DM and (non-DM) CA patients.
 ...
PMID:Type 2 diabetic patients may have a mild form of an injury response: a clinical research center study. 1200 58

Impaired insulin action is important in the pathophysiology of multiple metabolic abnormalities such as obesity and type 2 diabetes. Protein tyrosine phosphatase 1B (PTP1B) is considered a negative regulator of insulin signalling. This is best evidenced by studies on knockout mice showing that lack of PTP1B is associated with increased insulin sensitivity as well as resistance to obesity and in vitro studies whilst studies in animals and humans have given contradictory results. However, several studies support the notion that insulin signalling can be enhanced by the inhibition of PTP1B providing an attractive target for therapy against type 2 diabetes and obesity. In addition, recent genetic studies support the association between PTP1B with insulin resistance. The development of PTP1B inhibitors has already begun although it has become clear that is not easy to find both a selective, safe and effective PTP1B inhibitor. The objective of this paper is to review the current evidence of PTP1B in the pathophysiology of obesity, type 2 diabetes and cancer as well as in the treatment of these disorders.
 ...
PMID:Protein tyrosine phosphatase 1B: a new target for the treatment of obesity and associated co-morbidities. 1202 1

Diet is associated with 5 of the 10 leading causes of death in the U.S., including coronary heart disease, certain types of cancer, atherosclerosis, and type 2 diabetes. Physicians can play a pivotal role in promoting nutritional management of diabetes and other chronic diseases. Therefore, it is important that valid instruments are created so administrators can better assess the educational needs of prospective physicians, their practices, and patient outcomes. Two comparable studies, one year apart, were undertaken to create an instrument that measures nutritional competence and self-efficacy among prospective physicians. This paper: (a) describes the development of a nutrition self-efficacy scale (NSES) and (b) demonstrates reliability and validity of the NSES using Rasch modeling. It concludes with a discussion of potential contributions of this scale for assessing mastery of applied nutrition among prospective physicians.
 ...
PMID:Development of a nutrition self-efficacy scale for prospective physicians. 1202 74

Ample evidence supports a role for tumour necrosis factor alpha (TNFalpha) in the development of type 2 diabetes and cardiovascular disease. TNFalpha expression was found to be influenced by a -308G/A polymorphism in the promoter of the gene encoding TNFalpha (TNF). We investigated the contribution of this polymorphism to diabetes and cardiovascular mortality in a population-based cohort of 664 subjects aged 85 years and over (Leiden 85-plus Study). The -308G/A TNF promoter polymorphism was associated with the prevalence of diabetes in old age (P = 0.006). The risk of diabetes among subjects homozygous for the A-allele was estimated to be 4.6-fold (95% CI, 1.6-13.3) higher than among subjects homozygous for the common G-allele. The promoter polymorphism did not, however, predict mortality from all causes, cardiovascular diseases, cancer or infectious diseases during a 10-year follow-up period. In addition to the promoter polymorphism, TNFa and TNFc microsatellite genotypes were determined but these polymorphisms were not associated with morbidity or mortality. In conclusion, the -308G/A polymorphism in the TNF promoter is strongly associated with the risk of diabetes but not cardiovascular mortality in old age.
 ...
PMID:Association of the tumour necrosis factor alpha -308G/A polymorphism with the risk of diabetes in an elderly population-based cohort. 1205 58

The last 5 years have witnessed an explosion in the use of genes and cells as biomedicines. While primarily aimed at cancer, gene engineering and cell therapy strategies have additionally been used for Mendelian, neurodegenerative and metabolic disorders. The main focus of gene and cell therapy strategies in metabolism has been diabetes mellitus. This disease is a disorder of glucose homeostasis, either due to the immune-mediated eradication of pancreatic beta cells in the islets of Langerhans (type 1 diabetes) or resulting from insulin resistance and obesity syndromes where the insulin-producing capability of the beta cell is ultimately exhausted in the face of insensitivity to the effects of insulin in the peripheral glucose-utilising tissues (type 2 diabetes). A significant number of animal studies have demonstrated the potential in restoring normoglycaemia by islet transplantation in the context of immunoregulation achieved by gene transfer of immunoregulatory genes to allo- and xenogeneic islets ex vivo. Additionally, gene and cell therapy has also been used to induce tolerance to auto- and alloantigens and to generate the tolerant state in autoimmune rodent animal models of type 1 diabetes or rodent recipients of allogeneic/xenogeneic islet transplants. The achievements of gene and cell therapy in type 2 diabetes are less evident, but seminal studies promise that this modality can be relevant to treat and perhaps prevent the underlying causes of the disease. Here we present an overview of the current status of gene and cell therapy for type 1 and 2 diabetes and we propose potential therapeutic options that could be clinically useful. For type 1 diabetes, transplantation of islets engineered to evade or suppress the recipient immune response is the most readily-available technology today. A number of gene delivery vectors encoding proteins that impair a variety of immune cells have already been examined and proven versatile. More challenging but, nonetheless, just over the horizon are attempts to promote tolerance to islet allografts. Type 2 diabetes will likely require a better understanding of the processes that determine insulin sensitivity in the periphery. Targeting tissues such as muscle and fat with vectors encoding genes whose products promote insulin sensitivity and glucose uptake is an approach that does not carry with it the side-effects often associated with pharmacologic agents currently in use. In the end, progress in vector design, elucidation of antigen-specific immunity and insulin sensitivity will provide the framework for gene drug use in the treatment of type 1 and type 2 diabetes.
 ...
PMID:Gene and cell therapies for diabetes mellitus: strategies and clinical potential. 1210 44

Overweight and obesity have reached epidemic dimensions worldwide, mainly due to consumption of high energy diets and increased sedentary behaviour. Overweight and insufficient physical activity are clearly associated with cardiovascular diseases and type 2 diabetes. Evidence is also accumulating that they may also increase cancer risk, particularly in the colon, breast and endometrium. This effect seems to be mediated by alterations in the metabolism of endogenous hormones, including sex steroids and insulin, and levels of insulin-like growth factor(IGF)-I and IGF-binding proteins. In light of the beneficial effects of weight control and physical activity for cancer prevention, a healthy lifestyle, keeping a low body weight and exercising most days of the week, is recommended.
 ...
PMID:Weight control and physical activity in cancer prevention. 1211 60

The RecQ family of DNA helicases have potential roles in DNA repair, replication and/or recombination pathways. In humans, a defect in the RecQ family helicases encoded by the BLM, WRN and RECQ4 genes gives rise to Bloom's (BS), Werner's (WS) and Rothmund-Thomson (RTS) syndromes, respectively. These disorders are associated with cancer predisposition and/or premature aging. In Bloom's syndrome, affected individuals are predisposed to many types of cancer at an early age. Werner's syndrome is a premature aging disorder with a complex phenotype, which includes many age-related disorders that develop from puberty, including greying and thinning of the hair, bilateral cataract formation, type II diabetes mellitus, osteoporosis and atherosclerosis. The phenotype of Rothmund-Thomson syndrome patients also consists of some features associated with premature aging, as well as predispositon to certain cancers. Here, we discuss the molecular basis of these RecQ helicase-deficient disorders.
 ...
PMID:Premature aging in RecQ helicase-deficient human syndromes. 1220 42

Type 2 diabetes mellitus -- in which the body produces insufficient amounts of insulin or the insulin that is produced does not function properly to control blood glucose -- is an increasingly common disorder. Prospective clinical studies have proven the benefits of tighter glucose control in reducing the frequency and severity of complications of the disease, leading to the advocation of earlier and more aggressive use of insulin therapy. Given the reluctance of patients with type 2 diabetes to inject themselves with insulin, orally active insulin mimetics would be a major therapeutic advance. Here, we discuss recent progress in understanding the structure-function relationships of the insulin and insulin-like growth factor 1 (IGF1) receptors, their mechanism of activation and their implications for the design of insulin-receptor agonists for diabetes therapy and IGF1-receptor antagonists for cancer therapy.
 ...
PMID:Structural biology of insulin and IGF1 receptors: implications for drug design. 1236 Feb 55


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