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)

Diabetic retinopathy is a sight-threatening chronic complication of diabetes mellitus and is the leading cause of acquired blindness in adults. The -106C>T polymorphism in the promoter region of the aldose reductase (AR) gene has been shown to be associated with the susceptibility to diabetic nephropathy in type 2 diabetes, but the findings regarding the occurrence of diabetic retinopathy are conflicting. In this case-control study, we investigated whether the -106C>T polymorphism in the AR gene is involved in the development and progression of diabetic retinopathy in 579 Brazilians with type 2 diabetes (424 Caucasian- and 155 African-Brazilians). Patients underwent a clinical and laboratory evaluation consisting of a questionnaire, physical examination, assessment of diabetic complications and laboratory tests. Genotype analysis was performed using the polymerase chain reaction followed by digestion with restriction enzyme. Logistic regression analysis was used to control for independent risk factors associated with diabetic retinopathy. There were no differences in either genotype or allele frequencies for the -106C>T polymorphism between type 2 diabetic patients with or without diabetic retinopathy, in both ethnic groups. However, the CC genotype was associated with an increased risk of having proliferative diabetic retinopathy in Caucasian-Brazilians with type 2 diabetes (odds ratio (OR)=2.04; 95% confidence interval (CI)=1.21-3.45; P=0.007), independently of other risk factors associated with this complication. Thus, our results show that the -106CC genotype (-106C>T polymorphism) in the AR gene is related to the progression of diabetic retinopathy in Caucasian-Brazilians with type 2 diabetes.
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PMID:The -106CC genotype of the aldose reductase gene is associated with an increased risk of proliferative diabetic retinopathy in Caucasian-Brazilians with type 2 diabetes. 1654 77

The number of people with diabetes is increasing dramatically worldwide. The rising prevalence of obesity in childhood and adolescence has also been linked to a startling increase in the number of diagnosed cases of type 2 diabetes in these younger age groups. Despite the introduction of treatment strategies, diabetes remains a major cause of new-onset blindness, end-stage renal disease, and lower leg amputation, all of which contribute to the excess morbidity and mortality in people with diabetes. Furthermore, the management of diabetes-related complications generates substantial costs. In order that timely treatment can be given, it is essential that patients at risk for the development of diabetic microvascular complications are identified earlier. Diabetes duration and glycemic, blood pressure, and lipid control have consistently been shown to correlate with diabetic retinopathy, neuropathy, and nephropathy, but to date, the relationship of one diabetic microvascular complication to another has not been clearly described. A review of the literature has raised the question that apart from other known risk factors, there is a possible relationship among the diabetic microvascular complications themselves, and this appears to be much stronger than the sparse published data on it would suggest. A scoring system that can predict the development of diabetic microvascular complications may facilitate the early identification of those patients at risk and, consequently, have a positive impact on patients' quality of life and reduce the economic burden of diabetes and its complications.
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PMID:Diabetic microvascular complications--can the presence of one predict the development of another? 1679 74

The Centers for Disease Control and Prevention estimate that 6% of the US population meets diagnostic criteria for diabetes mellitus, with at least one third of this group being undiagnosed. A majority of adult blindness, renal insufficiency, and limb amputation may be directly attributed to diabetes. Although the incidence of type 1, autoimmune-mediated diabetes remains relatively stable, increasing age, physical inactivity, and obesity have produced explosive growth in insulin resistance and type 2 diabetes. A direct association between diabetes and atherothrombotic disease remains indisputable. However, recent data further suggest that even minor elevations of fasting plasma glucose, in "nondiabetic" subjects, increase cardiovascular risk. Alterations in hemostasis may play an important contributory role. Both hyperglycemia and hyperinsulinemia induce prothrombotic characteristics, including overexpression of vascular endothelial plasminogen activator inhibitor-1 (PAI-1), down-regulation of fibrinolysis, elevation of plasma coagulation proteins (ie, fibrinogen, factor VII, factor X), and enhanced platelet activation. Furthermore, endothelial dysfunction-characterized by an inflammatory phenotype-commonly accompanies diabetes. Given data supporting prothrombotic potential of both acute and chronic hyperglycemia, aggressive perioperative glucose control appears imperative.
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PMID:Hemostasis and glycemic control in the cardiac surgical patient. 1695 46

Severe combined hyperlipidaemia has occasionally been associated with infiltration of tissues in addition to arteries and the skin. We report a woman with Type 2 diabetes mellitus (DM) and severe combined hyperlipidaemia who developed retinal lipid infiltration, resulting in blindness. A 61-year-old woman with a 15-year history of Type 2 DM was admitted following a two-week history of progressive visual loss. Examination identified lipid infiltration into the retina. Phenotypically she had severe combined hyperlipidaemia with elevated IDL cholesterol and a broad beta band on lipoprotein electrophoresis, raising the possibility of familial dysbetalipoproteinaemia. However, gene sequencing analysis indicated that the patient was homozygous for the E3/E3 allele of the ApoE gene with no mutations detected in either the coding region or intron-exon boundaries. Her lipid profile improved following dietary therapy and gemfibrozil treatment, but this had little effect on either her fundal appearances or her visual acuity. Type 2 DM plays a vital role both in allowing expression of severe combined hyperlipoproteinaemia, in addition to serving as a risk factor for complications such as tissue infiltration.
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PMID:Severe combined hyperlipidaemia and retinal lipid infiltration in a patient with Type 2 diabetes mellitus. 1717 5

Diabetic retinopathy is the leading cause of blindness in working aged-adults in westernised countries. Diabetic macular oedema (DMO) is a manifestation of diabetic retinopathy and is the leading cause of the visual impairment that occurs with diabetic retinopathy. There are multiple ways of classifying DMO; however, none appear to be wholly satisfactory. DMO occurs more frequently in type 2 diabetes mellitus, and appears to be more prevalent as the duration of diabetes increases, and as the severity of diabetic retinopathy worsens. There are multiple risk factors in common with diabetic retinopathy, such as hyperglycaemia, hypertension and dyslipidaemia; however, specific factors such as the presence of renal disease appear to be more significantly associated with DMO. Whereas the gold standard for diagnosis of DMO is via clinical examination, there is considerable variability involved, and hence, this has led to the advent of more objective methods of quantifying the degree of retinal thickness, such as optical coherence tomography. Laser photocoagulation appears to be the only universally acceptable treatment of choice to date; however, this is a destructive therapy, and its side effects coupled with the suboptimal efficacy has led to the advent of potential new therapies which will undoubtedly compliment the existing approaches, in the future management of a patient with DMO.
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PMID:Diabetic macular oedema: a clinical overview. 1722 83

Depression affects millions of people in the United States. Drugs used to treat depression can lead to weight gain, which could predispose a person to type 2 diabetes. Also, certain medications that may be used to treat depression with psychotic features can lead to metabolic syndrome and new-onset diabetes. Diabetes is another chronic health care condition that affects millions of people in the United States. Diabetes is the leading cause of nontraumatic amputations and a leading cause of blindness. Both conditions can result in a lower quality of life. Clinicians face challenges in treating either condition, but can face greater ones when the conditions occur together. This article reviews the literature concerning depression and diabetes.
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PMID:Diabetes and depression: a review of the literature. 1727 May 91

Retinopathy is the most common microvascular complication of diabetes mellitus, and is an important cause of blindness worldwide. Clinical trials have demonstrated that tight metabolic control inhibits the progression of retinopathy. Good blood pressure control has been shown to be protective in type 2 diabetes, and it may also reduce proliferative retinopathy in type 1 diabetes. However, such control is often difficult to achieve in clinical practice, and may be associated with problems such as hypoglycaemia. New therapies are therefore needed to reduce the risk of retinopathy. There is growing evidence that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of diabetic retinopathy, and this has led to interest in RAS inhibitors as agents to prevent retinopathy. Several trials have suggested that ACE inhibitor therapy can inhibit progression of retinopathy. The Diabetic Retinopathy Candesartan Trials (DIRECT) Programme is currently investigating the effects of the angiotensin II receptor blocker candesartan on the incidence of retinopathy in type 1 diabetes and its progression in type 1 and type 2 diabetes. It is hoped that the results from such large-scale clinical trials will provide more specific information about the medical treatment of diabetic retinopathy.
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PMID:Prospects for angiotensin receptor blockers in diabetic retinopathy. 1732 27

Diabetes mellitus affects about 8% of the adult population. The estimated number of patients with diabetes, presently about 170 million people, is expected to increase by 50-70% within the next 25 years. Diabetes is an important component of the complex of 'common' cardiovascular risk factors, and is responsible for acceleration and worsening of atherothrombosis. Major cardiovascular events cause about 80% of the total mortality in diabetic patients. Diabetes also induces peculiar microangiopathic changes leading to diabetic nephropathy conducive to end-stage renal failure, and to diabetic retinopathy that may progress to vision loss and blindness. In terms of major cardiovascular events, coronary heart disease and ischaemic stroke are the main causes of morbidity and mortality in diabetic patients. Peripheral arterial disease frequently occurs, and is more likely to be conducive to critical limb ischaemia and amputation than in the absence of diabetes. Although there are a number of differences in the pathogenesis and clinical features of diabetic macroangiopathy and microangiopathy, these two entities often coexist and induce mutually worsening effects. Endothelial injury, dysfunction and damage are common starting points for both conditions. Causes of endothelial injury can be distinguished into those 'common' to nondiabetic atherothrombosis, such as hypertension, dyslipidaemia, smoking, hypercoagulability and platelet activation; and those more specific and in some cases 'unique' to diabetes and directly related to the metabolic derangement of the disease, such as (i) desulfation of glycosaminoglycans (GAGs) of the vascular matrix; (ii) formation of advanced glycation end-products (AGE) and their endothelial receptors (RAGE); (iii) oxidative and reductive stress; (iv) decline in nitric oxide production; (v) activation of the renin-angiotensin aldosterone system (RAAS); and (vi) endothelial inflammation caused by glucose, insulin, insulin precursors and AGE/RAGE. Prevention of major cardiovascular events with the antithrombotic agent aspirin (acetylsalicylic acid) is widely recommended, but reportedly underutilised in patients with diabetes. However, some data suggest that aspirin may be less effective than expected in preventing cardiovascular events and especially mortality in patients with diabetes, as well as in slowing progression of retinopathy. In contrast, a recent study found picotamide, a direct thromboxane inhibitor, to be superior to aspirin in diabetic patients. Clopidogrel was either equivalent or less active in diabetic versus nondiabetic patients, depending upon different clinical settings.Recent studies have shown that some GAG compounds are able to reduce micro- and macroalbuminuria in diabetic nephropathy, and hard exudates in diabetic retinopathy, but it is as yet unknown whether these agents also influence the natural history of microvascular complications of diabetes. Lifestyle changes and physical exercise are also essential in preventing cardiovascular events in diabetic patients. Available data on the control of the metabolic state and the main risk factors show that careful adjustment of blood sugar and glycated haemoglobin is more effective in counteracting microvascular damage than in preventing major cardiovascular events. The latter objective requires a more comprehensive approach to the whole constellation of risk factors both specific for diabetes and common to atherothrombosis. This approach includes lifestyle modifications, such as dietary changes and smoking cessation and the use of HMG-CoA reductase inhibitors (statins), which are able to correct the lipid status and to prevent major cardiovascular events independently of the baseline lipidaemic or cardiovascular status. Tight control of hypertension is essential to reduce not only major cardiovascular events but also microvascular complications. Among antihypertensive measures, blockade of the RAAS by means of ACE inhibitors or angiotensin II receptor antagonists recently emerged as a potentially polyvalent approach, not only for treating hypertension and reducing cardiovascular events, but also to prevent or reduce albuminuria, counteract diabetic nephropathy and lower the occurrence of new type 2 diabetes in individuals at risk.
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PMID:Approaches to prevention of cardiovascular complications and events in diabetes mellitus. 1748 45

Type 2 diabetes is characterized by abnormal metabolism of glucose and fat, due in part to resistance to the actions of insulin in peripheral tissues. If untreated it leads to several complications such as blindness, kidney failure, neuropathy and amputations. The benefit of exercise in diabetic patients is well known and recent research indicates that AMP activated protein kinase (AMPK) plays a major role in this exercise related effect. AMPK is considered as a master switch regulating glucose and lipid metabolism. The AMPK is an enzyme that works as a fuel gauge, being activated in conditions of high energy phosphate depletion. AMPK is also activated robustly by skeletal muscle contraction and myocardial ischaemia, and is involved in the stimulation of glucose transport and fatty acid oxidation produced by these stimuli. In liver, activation of AMPK results in enhanced fatty acid oxidation and decreased production of glucose, cholesterol, and triglycerides. The two leading diabetic drugs namely, metformin and rosiglitazone, show their metabolic effects partially through AMPK. These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.
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PMID:The role of AMP kinase in diabetes. 1749 63

Diabetes mellitus (DM) is a progressive disease characterized by insulin deficiency and insulin resistance or both. The fasting and post-prandial blood glucose is elevated, exposing the patient to acute and chronic complications (micro- and macro-vascular) leading to blindness, kidney failure, heart disease, stroke and amputations. Improving glycemic control has been demonstrated to lower the risk of these complications. Owing to the progressive nature of the disease, an evolving treatment strategy is necessary to maintain glycemic control. Varieties of new pharmacologic interventions are developed in past 5 years to treat people with diabetes. Several studies have been carried out covering different aspects of pharmacological interventions (newer and old drugs) along with the effects of weight loss, diet and exercise. Two categories of drugs have been used for the treatment of Diabetes Mellitus: the insulin and oral agents. Insulin analogues are molecules that differ from human insulin in amino acid sequence but bind to the insulin receptors and act similarly in function. This article provides an update of pharmacologic interventions for diabetes with practical overview of the new drug options, new insulin analogues, pharmacology, clinical efficacy, safety, dosing, cost, with specific examples of each and their background and side effects used to achieve tight glucose control. These agents have distinct characteristics that help in their selection for the treatment of type 1 and type 2 diabetes.
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PMID:Diabetes beyond insulin: review of new drugs for treatment of diabetes mellitus. 1763 Sep 27


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