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)

Diabetes mellitus is a chronic disease caused by inherited and/or acquired deficiency in production of insulin by the pancreas, and by resistance to insulin's effects. Such a deficiency results in increased concentrations of glucose and other metabolites in the blood, which in turn damages many of the body's systems, in particular the eyes, kidneys, nerves, heart and blood vessels. There are two major types of diabetes mellitus: Type 1 diabetes (insulin-dependent diabetes, IDDM or juvenile onset diabetes) and Type 2 diabetes (non-insulin-dependent diabetes, NIDDM or adult-onset). Chronic hyperglycemia is a major initiator of diabetic micro- and cardiovascular complications, such as retinopathy, neuropathy and nephropathy. Several hyperglycemia-induced mechanisms may induce vascular dysfunctions, which include increased polyol pathway flux, altered cellular redox state, increased formation of diacylglycerol (DAG) and the subsequent activation of protein kinase C (PKC) isoforms and accelerated non-enzymatic formation of advanced glycated end products. It is likely that each of these mechanisms may contribute to the known pathophysiologic features of diabetic complications. Others and we have shown that activation of the DAG-PKC pathway is associated with many vascular abnormalities in the retinal, renal, neural and cardiovascular tissues in diabetes mellitus. DAG-PKC pathway affects cardiovascular function in many ways, such as the regulation of endothelial permeability, vasoconstriction, extracellular matrix (ECM) synthesis/turnover, cell growth, angiogenesis, cytokine activation and leucocyte adhesion, to name a few. Increased DAG levels and PKC activity, especially alpha, beta1/2 and delta isoforms in retina, aorta, heart, renal glomeruli and circulating macrophages have been reported in diabetes. Increased PKC activation have been associated with changes in blood flow, basement membrane thickening, extracellular matrix expansion, increases in vascular permeability, abnormal angiogenesis, excessive apoptosis and changes in enzymatic activity alterations such as Na(+)-K(+)-ATPase, cPLA(2), PI3Kinase and MAP kinase. Inhibition of PKC, especially the beta1/2 isoform has been reported to prevent or normalize many vascular abnormalities in the tissues described above. Clinical studies have shown that ruboxistaurin, a PKCbeta isoform selective inhibitor, normalize endothelial dysfunction, renal glomerular filtration rate and prevented loss of visual acuity in diabetic patients. Thus, PKC activation involving several isoforms is likely to be responsible for some of the pathologies in diabetic retinopathy, nephropathy and cardiovascular disease. PKC isoform selective inhibitors are likely new therapeutics, which can delay the onset or stop the progression of diabetic vascular disease with very little side effects.
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PMID:The role of protein kinase C activation and the vascular complications of diabetes. 1757 31

Calorie restriction (CR) and alternate-day fasting (ADF) represent 2 different forms of dietary restriction. Although the effects of CR on chronic disease prevention were reviewed previously, the effects of ADF on chronic disease risk have yet to be summarized. Accordingly, we review here animal and human evidence concerning ADF and the risk of certain chronic diseases, such as type 2 diabetes, cardiovascular disease, and cancer. We also compare the magnitude of risk reduction resulting from ADF with that resulting from CR. In terms of diabetes risk, animal studies of ADF find lower diabetes incidence and lower fasting glucose and insulin concentrations, effects that are comparable to those of CR. Human trials to date have reported greater insulin-mediated glucose uptake but no effect on fasting glucose or insulin concentrations. In terms of cardiovascular disease risk, animal ADF data show lower total cholesterol and triacylglycerol concentrations, a lower heart rate, improved cardiac response to myocardial infarction, and lower blood pressure. The limited human evidence suggests higher HDL-cholesterol concentrations and lower triacylglycerol concentrations but no effect on blood pressure. In terms of cancer risk, there is no human evidence to date, yet animal studies found decreases in lymphoma incidence, longer survival after tumor inoculation, and lower rates of proliferation of several cell types. The findings in animals suggest that ADF may effectively modulate several risk factors, thereby preventing chronic disease, and that ADF may modulate disease risk to an extent similar to that of CR. More research is required to establish definitively the consequences of ADF.
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PMID:Alternate-day fasting and chronic disease prevention: a review of human and animal trials. 1761 57

The metabolic syndrome is a long-term process, explained by the interaction of genetic and environmental factors, that starts early in life and is involved in the pathophysiology of a large percentage of cases with type 2 diabetes and atherosclerosis. A number of clinical studies have demonstrated the importance of fat distribution and especially the contribution of visceral fat accumulation to the development of metabolic disorders. Visceral adipose tissue can be studied through different imaging techniques. The accumulation of visceral adipose tissue, as opposed to subcutaneous fat, increases the risk of developing metabolic disease and cardiovascular diseases (CVD). Visceral adipocytes secrete a variety of cytokines known as adipocytokines suggesting that adipose tissue is an endocrine organ that may affect the function of other organs. Weight loss, particularly a reduction in waist circumference, improves insulin sensitivity, lipid profile, and serum adipocytokines, reducing the risk of developing chronic disease and CVD. Waist circumference is a required component of metabolic syndrome under the International Diabetes Federation (IDF) criteria, rather than an optional component as used by other previous classifications. Studies have shown that using a lower waist circumference threshold within the context of metabolic syndrome increases the prevalence, but decreases the risk of mortality and type 2 diabetes. It is possible that waist circumference acts as a marker for other risk factors. These findings reinforce the notion that reductions in visceral adipose tissue should be a primary aim of strategies designed to reduce health risks associated with metabolic syndrome.
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PMID:Metabolic syndrome and adipose tissue: new clinical aspects and therapeutic targets. 1762 47

C-reactive protein (CRP) is one of the acute-phase proteins in inflammation and CRP serum concentrations are therefore of interest. Data for high-sensitivity CRP (hs-CRP) with a low detection limit of approximately 0.04 mg/L have become available over the past decade and research has shown a link between high concentrations of hs-CRP and obesity as well as smoking. Expanded adipose tissue is in fact known to secrete proinflammatory cytokines which enhance hepatic synthesis of CRP. Moderate alcohol consumption and high physical activity have been associated with low levels of hs-CRP, but the evidence in these cases is not conclusive. It has been suggested that hs-CRP is an independent marker of the risk of cardiovascular disease, but the predictive capacity remains controversial. However, many prospective studies have observed increased risk of type 2 diabetes mellitus associated with high concentrations of hs-CRP, independent of obesity and other cardiovascular risk factors. On the other hand, no measurable increase in the risk associated with high levels of hs-CRP was observed with multivariate adjustment in several studies. A number of authors have reported that high concentrations of hs-CRP are associated with increased risks of colorectal and other cancers, but the findings again are inconsistent. Diet and hs-CRP are also of increasing research interest. High intakes of carotenoids and vitamin C, but not of vitamin E, seem to decrease the level of circulating hs-CRP. In addition, high consumption of vegetables and fruit are associated with lower levels of circulating hs-CRP, perhaps by exerting anti-inflammatory effects. Both mechanistic and epidemiologic studies regarding dietary factors and low-grade inflammation are necessary to add to our knowledge of dietary influence on chronic disease development.
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PMID:Impact of C-reactive protein on disease risk and its relation to dietary factors. 1769 26

Type 2 diabetes mellitus is a common chronic disease that causes significant morbidity and mortality worldwide. The primary goal of treatment is to target glycemic control by maintaining the glycosylated hemoglobin level near 6-7% without predisposing patients to hypoglycemia. Diabetes results from a combination of increased hepatic glucose production, decreased insulin secretion from beta cells, and insulin resistance in the peripheral tissues. Currently available antidiabetic agents work by different mechanisms to lower blood glucose levels. Unfortunately, each of them has its tolerability and safety concerns that limit its use and dose titration. Sitagliptin is the first antidiabetic agent from the class of dipeptidyl peptidase-4 enzyme inhibitors. It increases the amount of circulating incretins, which stimulate insulin secretion and inhibit glucose production. Sitagliptin was approved by the US Food and Drug Administration (FDA) for use with diet and exercise to improve glycemic control in adult patients with type 2 diabetes. It can be used alone or in combination with metformin or a thiazolidinedione (pioglitazone or rosiglitazone) when treatment with either drug alone provides inadequate glucose control. The usual adult dose is 100 mg once daily. A dose of 25-50 mg once daily is recommended for patients with moderate-to-severe renal impairment. In randomized, placebo-controlled trials that lasted for up to 6 months, sitagliptin lowered glycosylated hemoglobin levels by 0.5-0.8%. In a 52-week clinical trial, sitagliptin was shown to be noninferior to glipizide as an add-on agent in patients inadequately controlled on metformin alone. Sitagliptin was well tolerated with the most common side effects being gastrointestinal complaints (up to 16%), including abdominal pain, nausea and diarrhea; hypoglycemia and body weight gain occurred at similar rates compared with placebo. Overall, sitagliptin provides a treatment option for patients with type 2 diabetes as a monotherapy, or as an adjunct to metformin or a thiazolidinedione when patients achieve inadequate glycemic control while on either of the agents. It is also an alternative therapy for those patients who have contraindications or intolerability to other antidiabetic agents.
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PMID:Sitagliptin: a novel drug for the treatment of type 2 diabetes. 1770 Mar 85

(1) Diabetes is a chronic disease whose incidence is increasing worldwide. The long-term complications of diabetes place a large health and economic burden onto individuals, their families and communities as a whole.(2) Guidelines on the prevention of diabetes recommend lifestyle changes such as smoking cessation and weight loss to decrease type 2 diabetes incidence in patients with impaired glucose tolerance or impaired fasting glucose.(3) The role of lifestyle changes and weight loss in preventing diabetes has been proven in large, randomized, controlled clinical trials. To date, the evidence in favor of pharmacological methods is less robust; however, encouraging results obtained so far suggest a promising future role for these agents.(4) Several oral hypoglycemic agents and the antiobesity drug orlistat have been shown to significantly decrease progression to diabetes. The role of other agents such as statins, oestrogen and antihypertensive agents remains to be clarified in additional well-designed studies of diabetes prevention.
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PMID:Pharmacological interventions in the prevention of type 2 diabetes. 1794 Apr 36

Type 2 diabetes mellitus appears to directly impair cognition and brain function, independent of its associated cardiovascular disease. This is supported by the presence of similar findings among adults with insulin resistance (pre-diabetes) and obese children with type 2 diabetes, years before overt cardiovascular disease. Hippocampal based memory performance is impaired early in the disease, although deficits in executive function, attention, and psychomotor speed are also seen in more chronic disease and/or poorer disease control, particularly in the presence of co-morbidities such as hypertension. Although there has been some speculation as to possible links between diabetes and Alzheimer's Disease based on associations found in population studies, no convincing empirical evidence has been put forth and brain autopsy studies, the gold standard of Alzheimer's diagnosis, have not supported such a link. Future studies should focus on understanding the mechanisms for the cognitive impairments associated with type 2 diabetes. We propose that insulin resistance-associated impairments in vascular reactivity and endothelial function are possible candidates as they may impact substrate delivery across the blood-brain-barrier. These are important issues given the obesity epidemic and the associated rising prevalence of insulin resistance and type 2 diabetes.
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PMID:Diabetes, sugar-coated but harmful to the brain. 1802 86

Diabetes mellitus is a chronic disease with an increasing prevalence. Appropriate treatment of the disease and prevention of chronic complications reduce morbidity and mortality in a cost-effective manner. These actions should be measured through the use of validated indicators for quality of care. The goal of this study was to assess the quality of care in diabetic patients under pharmacologic treatment in a private university hospital. A retrospective study was conducted in adult patients who bought insulin or oral hypoglycemic agents during a 3 month period; demographic and clinical data were obtained for 12 consecutive months following the buying period. The study included 305 adult patients; most were males (60%), with type 2 diabetes (95%), and using oral hipoglycemic agents (86%). Control of blood pressure was registered in 80%, foot exam in 5%, eye exam in 27%, HbA1C blood level in 85%, complete lipid profile in 82%, microalbuminuria in 27% and creatinine clearance in 22% of patients, respectively. Mean values were HbA1C 7.1(+/- 1.6)%, and < or = 7% in 66%, LDL 113 (+/- 33.6) mg/dl and <100 mg/dl in 30%, BP 136-79 mm Hg and < 130-80 mm Hg in 46% of patients, respectively. This study emphasizes the need for quality of care assessment through validated indicators and points out the aspects that should be improved within a health care system.
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PMID:[Quality of care in diabetic patients receiving pharmacologic treatment]. 1805 Dec 22

Type 2 diabetes mellitus is a serious chronic disease that is very prevalent in the developed world. The etiology of this disease is not well understood. Recently, the role of the innate immune system in the pathogenesis of type 2 diabetes and its complications has received a great deal of attention. Cytokines, acute phase proteins, and phagocytes have been implicated in this model. Resistance training has known benefits in type 2 diabetic patients and older adults, such as improved insulin action, insulin sensitivity, fasting blood glucose and insulin, and glucose tolerance levels. Actions of pro-inflammatory mediators linked to dysregulated innate immune activity have been associated with type 2 diabetes. The immunomodulatory effects of exercise, and in particular approaches such as resistance training, may provide a strategy to counter these pro-inflammatory effectors. However, the effects of resistance training on innate immunity have not been studied extensively in adults with type 2 diabetes or in older adults who are at increased risk for development of type 2 diabetes. This review discusses the possibility that resistance training may have positive effects on innate immunity in this population and so may provide benefits in addition to improving strength and functional abilities. In particular, the potential of resistance training to modulate pro-inflammatory parameters associated with type 2 diabetes, as a strategy that could provide multiple beneficial health outcomes, is addressed.
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PMID:Type 2 diabetes mellitus, resistance training, and innate immunity: is there a common link? 1805 74

Diabetes mellitus is a chronic disease characterized by an overproduction of reactive oxygen species, which perturbs zinc metabolism and promotes the onset of cardiovascular disease (CVD) in diabetic patients. Metallothioneins (MT) are cysteine-rich metal-binding proteins which, by means of their antioxidant and zinc-buffering properties, might prevent the development of diabetic cardiovascular complications. A recent investigation shows that a polymorphism (+647 A/C) in the human MT-1A gene, affects the intracellular zinc ion release (iZnR) from the proteins and is associated with longevity in Italian population. The aim of the present study is to assess the involvement of +647 A/C and +1245 A/G MT1A polymorphisms with the susceptibility to type 2 diabetes (DM2) and cardiovascular complications. The study included 694 old individuals: 242 old healthy controls, 217 DM2 patients without clinical evidence of CVD (DNC) and 235 diabetic patients with diagnosis of CVD (DCVD). +647 A/C MT1A polymorphism, but not the second SNP, was associated with DM2. C allele carriers were more prevalent in DNC and DCVD patients than in control group (OR=1.37, p=0.034; OR=1.54, p=0.002, respectively). C+ carriers was associated with higher glycemia and glycosylated hemoglobin in DCVD patients, but not in DNC or control subjects. No differences in plasma zinc, but a modulation of MT levels and iZnR in PBMCs were observed in DCVD cohort when related to +647 A/C MT1A polymorphism. In summary, this work provides novel evidence on the association of the +647 A/C MT1A polymorphism with DM2. Moreover, C+ carriers in DCVD patients presented a worse glycemic control, a reduced iZnR and a higher MT levels, suggesting a possible role of MT in diabetic cardiovascular complications.
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PMID:+647 A/C and +1245 MT1A polymorphisms in the susceptibility of diabetes mellitus and cardiovascular complications. 1832 46


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