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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This century brings a pandemic of diabetes mellitus, with marked increases in early-accelerated atherosclerosis. When asymptomatic patients with diabetes present for evaluation, they have more extensive coronary atherosclerosis, lower ejection fractions, higher rates of previous cardiac events, and more silent ischemia than the normal population. The challenge faced by clinicians is to accurately identify asymptomatic patients with diabetes who have significant coronary ischemia that would benefit from revascularization. Diabetic endovascular disease has all the high-risk features to promote atherosclerosis and coronary occlusion: hyperglycemia-induced endothelial dysfunction, impaired fibrinolysis, increased platelet aggregation, plaque instability, dysfunctional arterial remodeling, and fibrotic and calcified coronary arteries. The optimal revascularization strategy for patients with diabetes is an ongoing debate. The advent of drug-eluting stents has changed the landscape, and some have suggested that the current role of coronary artery bypass grafting may be reduced by as much as 46%. Unfortunately, there is limited evidence from randomized, controlled trials that reflects current practice and could guide clinicians in making the best choices for patients with diabetes and coronary disease. It is hoped that ongoing trials--including Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D), Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM), and Coronary Artery Revascularisation in Diabetes (CARDia)--will answer many of the remaining questions. Still, the best treatment includes lifestyle modification and early prevention strategies with global risk reduction.
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PMID:Diabetic endovascular disease: role of coronary artery revascularization. 1730 63

Although physical activity has been associated with cardiovascular mortality reduction in type-1 diabetes (DM1) patients, many points in the topic 'exercise' deserve a closer look. For example: contradictory data have been reported regarding the benefits of physical activity on metabolic control in these patients. Still contradictory is the type of exercise that brings more benefit in this group. Another issue is the best way of reducing insulin doses for exercise. This article intent to discuss these topics. The effect of exercise on metabolic control in DM1 is still contradictory. Some authors show a beneficial effect on glycated hemoglobin (A1c) and others do not. Another point to be analized is which type of exercise is better for these patients: aerobic or of resistance. There is a lack of information related to the effect of resistance exercises without the aerobic training on metabolic control in type-1 diabetes. The effect of exercise on lipid profile in DM1 is another issue. The intensity and duration of the exercises, the level of physical activity, the duration of the disease and the presence of cronic complications are some points that might be taken into consideration before starting an exercise program. Guidelines for the reduction in insulin dose or the use of carbohydrate are strategies to avoid hypoglycemia related to exercises. Hydration and self-monitored blood glucose levels are also very important topics. This article will also discuss the clinical evaluation before doing any exercise.
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PMID:[The role of exercise in the treatment of type 1 diabetes]. 1843 36

Diabetes is widely believed to predispose to serious infections. However, the mechanisms linking diabetes and immunosuppression are not well defined. One potential mediator of the altered defence mechanisms is hyperglycaemia. It has been identified as the main factor contributing to the development of diseases associated with diabetes mellitus. In this study we analyse the immune response in diabetes and the direct effect of hyperglycaemia on T and B lymphocyte reactivity. Diabetes induced an early decrease in IgG levels in the secondary response. However, both primary responses against a T-cell-dependent or independent antigen were affected after 6 months of diabetes induction. T- and B- cell proliferation was only decreased at this time. To gain insight into the potential mechanisms involved, we evaluated the influence of hyperglycaemia over the immune response. Pre-incubation of lymph node and spleen cells in a high glucose (HG) containing medium led to a significant time- and dose-dependent decrease in T- and B-cell proliferation. This effect was associated with the presence of HG-derived supernatants. Still viable cells after HG exposition were able to improve their proliferative response when cultured with the mitogen in a fresh standard medium. HG diminished cell viability, increased apoptosis and induced oxidative stress in lymphocytes. These results indicate that HG concentrations can directly affect lymphoid cell growth. An increase in oxidative stress would be implicated in this deleterious effect. The possibility that prolonged exposure to pathologically HG concentrations would result in the immunosuppressive state observed in diabetes is also discussed.
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PMID:Impaired immune responses in streptozotocin-induced type I diabetes in mice. Involvement of high glucose. 1877 65

The biochemical mechanisms underlying glucose-stimulated insulin secretion from pancreatic beta-cells are not completely understood. To identify metabolic disturbances in beta-cells that impair glucose-stimulated insulin secretion, we compared two INS-1-derived clonal beta-cell lines, which are glucose-responsive (832/13 cells) or glucose-unresponsive (832/2 cells). To this end, we analyzed a number of parameters in glycolytic and mitochondrial metabolism, including mRNA expression of genes involved in cellular energy metabolism. We found that despite a marked impairment of glucose-stimulated insulin secretion, 832/2 cells exhibited a higher rate of glycolysis. Still, no glucose-induced increases in respiratory rate, ATP production, or respiratory chain complex I, III, and IV activities were seen in the 832/2 cells. Instead, 832/2 cells, which expressed lactate dehydrogenase A, released lactate regardless of ambient glucose concentrations. In contrast, the glucose-responsive 832/13 line lacked lactate dehydrogenase and did not produce lactate. Accordingly, in 832/2 cells mRNA expression of genes for glycolytic enzymes were up-regulated, whereas mitochondria-related genes were down-regulated. This could account for a Warburg-like effect in the 832/2 cell clone, lacking in 832/13 cells as well as primary beta-cells. In human islets, mRNA expression of genes such as lactate dehydrogenase A and hexokinase I correlated positively with HbA(1c) levels, reflecting perturbed long term glucose homeostasis, whereas that of Slc2a2 (glucose transporter 2) correlated negatively with HbA(1c) and thus better metabolic control. We conclude that tight metabolic regulation enhancing mitochondrial metabolism and restricting glycolysis in 832/13 cells is required for clonal beta-cells to secrete insulin robustly in response to glucose. Moreover, a similar expression pattern of genes controlling glycolytic and mitochondrial metabolism in clonal beta-cells and human islets was observed, suggesting that a similar prioritization of mitochondrial metabolism is required in healthy human beta-cells. The 832 beta-cell lines may be helpful tools to resolve metabolic perturbations occurring in Type 2 diabetes.
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PMID:Tight coupling between glucose and mitochondrial metabolism in clonal beta-cells is required for robust insulin secretion. 1979 55

Pancreatic beta-cells are the sole source of insulin, the major hormonal regulator of glycaemia. In physiological and pathological conditions with increased insulin demand, beta-cells adjust their insulin output either through increased insulin secretory granule (ISG) biogenesis and secretion, or hyperplasia. Failure of these compensatory mechanisms eventually results in hyperglycaemia and diabetes mellitus. Both of these major adaptive behaviours are positively regulated by several extrinsic factors, such as glucose, GLP-1, insulin and growth hormones (GH). Still unclear, however, it is how beta-cells in response to these stimuli opt for one or the other strategy at a given time. Here we review recent advances concerning the factors and pathways that enhance ISG biogenesis and beta-cell replication, and propose the existence of 'switch factors' that play a key role in regulating the shift between these two adaptive responses.
Diabetes Obes Metab 2009 Nov
PMID:beta-Cells at the crossroads: choosing between insulin granule production and proliferation. 1981 89

This perspective is part of an ongoing series of articles that describe the drugs that were dropped from clinical development during the previous year. This paper focuses on those drugs that were discontinued in 2008. The drugs represent a diverse collection of compounds targeted at diseases including cancer, diabetes, infections, arthritis, HIV, restenosis, allergies, anaemia, osteoporosis, wound healing, and growth deficiency. No consistent theme is apparent that accounts for the diversity of discontinued drugs. Still, this diversity, coupled with the numbers of novel drugs that were approved in 2008 suggests a healthy ongoing drug development process.
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PMID:Discontinued biological drugs in 2008. 1991 30

Overall lowering of glucose is of pivotal importance in the treatment of diabetes, with proven beneficial effects on microvascular and macrovascular outcomes. Still, patients with similar glycosylated hemoglobin levels and mean glucose values can have markedly different daily glucose excursions. The role of this glucose variability in pathophysiological pathways is the subject of debate. It is strongly related to oxidative stress in in vitro, animal, and human studies in an experimental setting. However, in real-life human studies including type 1 and type 2 diabetes patients, there is neither a reproducible relation with oxidative stress nor a correlation between short-term glucose variability and retinopathy, nephropathy, or neuropathy. On the other hand, there is some evidence that long-term glycemic variability might be related to microvascular complications in type 1 and type 2 diabetes. Regarding mortality, a convincing relationship with short-term glucose variability has only been demonstrated in nondiabetic, critically ill patients. Also, glucose variability may have a role in the prediction of severe hypoglycemia. In this review, we first provide an overview of the various methods to measure glucose variability. Second, we review current literature regarding glucose variability and its relation to oxidative stress, long-term diabetic complications, and hypoglycemia. Finally, we make recommendations on whether and how to target glucose variability, concluding that at present we lack both the compelling evidence and the means to target glucose variability separately from all efforts to lower mean glucose while avoiding hypoglycemia.
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PMID:Glucose variability; does it matter? 1996 12

Type 1 diabetes (T1DM) is characterized by loss of virtually all endogenous insulin secretion. If residual insulin secretion is preserved, this will lead to improved metabolic balance, less acute and late complications, improved quality of life, and, in case of pronounced improvement of residual insulin secretion, complete remission and even cure of the disease. Immune suppression or immune modulation have been demonstrated as a proof of principle to stop/decrease the destructive process and thereby preserve beta-cell function. Several methods to save residual beta-cell function have been tried for more than three decades with little or no evidence of efficacy. Positive effects have been seen mainly in adult patients but have been minimal or absent in children with diabetes. Furthermore, the safety of these immune interventions and/or their benefit to risk relationships have not been found to justify clinical use. More specific immune modulation with anti-CD3 monoclonal antibodies has resulted in more encouraging postponement of C-peptide decline, but with frequent and serious adverse effects. Still more promising are the autoantigen therapies, of which glutamic acid decarboxylase (GAD) vaccination has shown significant preservation of residual insulin secretion in 10-18-year-old type 1 diabetes patients with recent onset. Efficacy was most impressive in the subgroup of patients with diabetes of short duration (<3 months). The treatment was simple, well tolerated, and showed no treatment-related adverse events. If these results can be confirmed, there is a realistic hope that GAD vaccination, perhaps in combination with vaccinations with other autoantigens and/or other therapies, will result in remission for some patients. The prospects of cure and prevention of T1DM will become less remote.
J Diabetes Sci Technol 2009 Mar 01
PMID:The role of immunomodulation therapy in autoimmune diabetes. 2014 63

Epidemiologic data indicate a continuous relationship between hemoglobin A1c (HbA1c) and risk for microvascular and macrovascular complications of diabetes. Intensive glycemic control reduces risk of microvascular complications in Type 1 and Type 2 diabetes, and long-term treatment and follow-up studies have shown that initial intensive control is associated with reduced cardiovascular risk. Recent intervention trials in older, high-risk patients with Type 2 diabetes have not shown a benefit of intensive control in reducing cardiovascular risk over a rather short-term follow-up period of up to 5 years, with some data indicating that intensive control accompanied by hypoglycemia is detrimental in patients with high cardiovascular risk. Indeed, hypoglycemia with current antidiabetic agents--primarily insulin and sulphonylureas--is the main limiting factor in achieving desirable levels of glycemic control. Still, the goal in treating both Type 1 and Type 2 diabetes should be to safely get HbA1c as close to normal as possible. In Type 2 diabetes, this goal should be tempered for the time being in patients with shorter life expectancy or co-existing cardiovascular disease or other co-morbidities, in whom a target of 7.0-7.5% may be advisable until we can demonstrate that lower targets in such patients can be safely achieved. Newer agents with lower risk of hypoglycemia--e.g., insulin analogues, incretin mimetics and incretin enhancers-may form an integral component of strategies for safely achieving lower HbA1c levels.
J Diabetes Complications
PMID:The importance of glycemic control: how low should we go with HbA1c? Start early, go safe, go low. 2046 72

1-methylnicotinamide (MNA) is a primary metabolite of nicotinamide. In recent years several activities of MNA have been described, such as anti-inflammatory activity in skin diseases, induction of prostacyclin synthesis via COX-2, aortal endothelium protection in diabetes and hypertriglyceridaemia and increasing survival rate of diabetic rats. The aim of the present study was to verify whether the increased survival rate of diabetic animals could be explained by anti-hyperglycaemic activity of MNA and/or by its protective effects on vascular endothelium. We used Sprague-Dawley male rats with an experimental streptozotocin diabetes. The animals received either MNA or pure drinking water. At the particular time intervals groups of rats were sacrificed and the blood was collected. We have shown that MNA increases levels of PGI2 in diabetic rats, but the effect is limited only to the early stage of diabetes. We were unable to prove anti-inflammatory effects of MNA, as it did not affect increased TNF-alpha in diabetic animals. We have confirmed our previous observations that MNA improved survival of diabetic animals, but contrary to our previous study, this effect was not accompanied by improvement in the parameters of long-term glycaemic control. Overall, we conclude that anti-diabetic activity of MNA manifested in the improved lifespan of diabetic animals is rather due to MNA pro-prostacyclin activity, and it may not be substantially related to glycaemic control in diabetes. Still other potential mechanism(s) await further elucidation.
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PMID:1-methylnicotinamide effects on the selected markers of endothelial function, inflammation and haemostasis in diabetic rats. 2051 41


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