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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 diabetes mellitus is a prevalent disease in Westernised society, and more than 50% of individuals with diabetes mellitus die from cardiovascular causes. The underlying metabolic defect of type 2 diabetes mellitus is a combination of insulin resistance and decreased secretion of insulin by pancreatic beta-cells. Insulin resistance commonly precedes the onset of type 2 diabetes mellitus and is usually associated with a metabolic syndrome including hypertension, dyslipidaemia and obesity. Treatment of known cardiovascular risk factors, including hyperglycaemia, dyslipidaemia, hypertension and smoking, plays a key role in delaying the onset and progression of coronary heart disease (CHD) and other forms of atherosclerosis in patients with diabetes mellitus. Sulphonylureas should be used with caution in patients with CHD but aspirin (acetylsalicylic acid), beta-blockers and ACE inhibitors play an important role in the medical management of patients with established coronary artery disease and diabetes mellitus. Patients with diabetes mellitus represent a higher risk group of patients after both percutaneous and surgical coronary revascularisation and the decision regarding the choice of revascularisation procedure should take into account angiographic characteristics, clinical status and patient preference. Patients presenting with diabetes mellitus and acute myocardial infarction should be considered for reperfusion therapy with either urgent thrombolytic therapy or primary percutaneous coronary intervention.
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PMID:Optimisation of the management of patients with coronary heart disease and type 2 diabetes mellitus. 1139 41

Obesity is one of the most important predictors and causes of such lifestyle diseases as metabolic syndrome, type 2 diabetes, and cardiovascular disease. It is thus imperative to follow the trend longitudinally in the population. Measurement of obesity in children and adolescents is difficult; many studies use the body mass index as a measure, regardless of the fact that it is inappropriate. Skinfolds or the ponderal index should be used, instead. Recent Danish studies suggest that the incidence of childhood and adolescent obesity is increasing and that those who are overweight are even more so today than earlier. Obesity is caused by a number of factors, genetic, social, environmental, and lifestyle, all of which play an important role. One of the main causes of the increase in childhood obesity in Denmark today is the lower level of physical activity than formerly. The prospects for the future are an increase in obesity and incidence of lifestyle diseases with a poorer quality of life and a shorter life time expectancy.
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PMID:[Obesity among children--with particular reference to Danish circumstances]. 1140 67

Dyslipidemia emerges as an important modifiable risk factor for cardiovascular disease in diabetes mellitus, especially as part of the metabolic syndrome in type 2 diabetes. In type 1 diabetes mellitus, tight glucose regulation usually will correct dyslipidemia. Both total cholesterol and triglyceride levels predict cardiovascular disease in diabetes, and HDL-cholesterol may prove to be an even better predictor. In type 2 diabetes, increased triglyceride and reduced HDL-cholesterol levels are the key characteristics of dyslipidemia. Increased hepatic VLDL production and impaired catabolism of triglyceride-rich particles contribute to hypertriglyceridemia. Subsequent formation of small dense LDL particles leads to increased atherogenicity. Small dense LDL particles have a longer circulation time, are susceptible to glycoxidation, and are taken up by macrophages and the vessel wall. Post-hoc analysis of diabetic subgroups in primary and secondary prevention trials suggest that individuals with diabetes may enjoy substantial cardiovascular risk reduction from lipid-lowering therapy. Trials prospectively addressing the benefit of lipid lowering therapy in diabetes are under way. Target levels for lipid lowering therapy in diabetes at present stem from pathophysiological plausibility rather than from clinical proof. Intensive lipid-lowering with a statin in adequate dosage or a combination of a statin and a fibrate may be used to lower LDL-cholesterol levels to values < 2.6 mmol/l and triglyceride levels to < 1.7 mmol/l, a value at which few small dense LDL particles remain in circulation. Effective medication to raise HDL-cholesterol levels adequately are not yet available for clinical use. Treatment of diabetic dyslipidemia should be as simple as possible, given the polypharmacy that is often necessary for the patient with diabetes. Therefore, single treatment with a statin in adequate dosage is the first choice.
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PMID:Lipid-lowering therapy in diabetes mellitus. 1141 34

Insulin resistance was already suspected in the thirties from clinical observations in diabetic patients, then better appreciated in the early sixties with the development of insulin radioimmunoassay, and finally confirmed in the last 20 years by using various sophisticated methods able to quantify insulin action. First demonstrated in obese and/or type 2 diabetic patients, the diminution of insulin sensitivity may in fact concern a much larger population. The concept of insulin sensitivity gained a considerable importance when Reaven, in 1988, emphasized the role of insulin resistance in different human diseases. The metabolic syndrome or syndrome X is characterized by the association of various cardiovascular risk factors (among which impaired glucose tolerance, arterial hypertension and dyslipidaemias), all closely linked to insulin resistance which is indeed the core of the syndrome. Even if insulin action signalling appears to be rather complex and the mechanisms leading to insulin resistance still largely unknown, it is essential to develop pharmacological or non pharmacological strategies to improve insulin sensitivity for treating insulin-resistant individuals. Such an approach should allow not only to provide a better blood glucose control in patients with type 2 diabetes, but also to improve the cardiovascular prognosis of numerous patients, with or without diabetes mellitus, who have the metabolic syndrome.
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PMID:[The insulin sensitivity concept]. 1145 10

Several studies support the association between postprandially elevated triglyceride levels and atherosclerosis. Histological and cell culture investigations revealed, that triglyceride rich postprandial lipoproteins are taken up by macrophages and smooth muscle cells and are detectable as part of foam cells in vascular lesions. Remnant particles, generated by lipolysis of postprandial lipoproteins in vitro and fatty acids increase the permeability of the endothelium and are cytotoxic for endothelial cells. Besides these morphological changes of cells, lipoproteins have been shown to exert effects on cellular functions like the expression of membrane proteins and the production or release of several bioactive substances regulating communication with blood cells and other cell systems of the vascular wall, blood pressure and hemostasis. This review concentrates on the influence of postprandial lipoproteins on factors involved in the interaction of endothelial cells with blood leukocytes and factors mediating blood pressure regulation. Increased expression of adhesion molecules has been detected immunehistochemically in atherosclerotic plaques in animals and humans. It was demonstrated that patients with elevated triglyceride levels have increased levels of soluble adhesion molecules. Furthermore, postprandial lipoproteins were shown to induce membrane expression of adhesion molecules. This effect seems to be at least in part mediated by the oxidative modification of the particles. Accordingly chylomicrons separated after ingestion of safflower oil, rich in polyunsaturated linoleic acid, induced higher adhesion molecule expression at higher oxidant concentration compared with chylomicrons separated after ingestion of olive oil, rich in monounsaturated oleic acid. Several authors described effects of fatty acids on the expression of adhesion molecules. On the one hand, they may exert stimulatory effects as such, on the other hand cytokine induced adhesion molecule expression may be enhanced by certain fatty acids and inhibited by others, implying an interference with signal transduction processes. Effects of lipoproteins on vasoactive substances seem to be implicated in endothelial dysfunction, too. The endothelium-derived relaxing factor nitric oxide (NO) has gained increasingly attention in the last two decades and is regarded as protective against hypertension and atherosclerosis. It was demonstrated that chylomicrons and their remnants inhibited endothelium-dependent relaxations in isolated aortas. Vasodilatatory responses and nitric oxide metabolism were shown to be affected by the amount and composition of dietary fat. Cell culture experiments revealed modulation of NO release by certain fatty acids. Plasma levels of endothelin-1, a strong vasoconstrictor, have been shown to be increased in patients with type 2 diabetes and metabolic syndrome, respectively. Postprandially elevated triglycerides increased endothelin-levels in addition to insulin in patients with metabolic syndrome. In summary, there is evidence that the association between postprandial triglycerides and the metabolic syndrome is driven by direct influences on endothelial functions because plasma triglyceride levels are associated with levels of humoral risk markers of endothelial origin, and postprandial lipoproteins stimulate the release and/or expression of endothelial mediators in vitro, which induce atherogenesis and hypertension.
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PMID:Postprandial triglycerides and endothelial function. 1145 41

Functional and organic abnormalities in small unmyelinated C fibers are the hallmark of type 2 diabetes. These may be silent clinically or present with burning feet, neurovascular abnormalities, wherein warm, cold, and heat pain thresholds are disturbed in association with impairment in skin blood flow and loss of PGP 9.5 immunostaining nerves in the skin. There is a dysfunctional phase preceding organic structural damage to the neurovascular unit. It coexists with elements of the metabolic syndrome, particularly insulin resistance (IR), elevated systolic blood pressure, and diabetic dyslipidemia i.e. dysfunction of the neurovascular unit may contribute to IR due to compromised blood flow with decreased delivery of fuels to their target tissues. If this proves to be the case, it will become important to re-focus energies on the defective neuropeptidergic regulation of blood flow as an approach to ameliorating diabetes. Because there is a functional phase that precedes structural damage, reversibility of the defect is achievable.
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PMID:Small fiber neuropathy and neurovascular disturbances in diabetes mellitus. 1146 May 91

LADA or type 1.5 diabetes is a slowly progressive form of autoimmune diabetes of adults and represents a considerable proportion (about 5-10%) of all diabetic patients. Associations with high risk HLA genotypes and autoimmune phenomena (GAD, IA2, ICA) show similarities with type 1 diabetes, but phenotypical characteristics of these patients do not allow the correct identification without screening of GAD antibodies. The relatively low antibody titers against islet-cell antigens in LADA patients may be sign of a less aggressive form of autoimmune diabetes and could be responsible for the long non-insulin requirement phase of this diabetes type. Similar as in prediabetic relatives of type 1 diabetic patients the risk for beta cell failure in adult "type 2 diabetic" patients increases with the number of antibodies positive. Consequently, low titers of GAD--in particular in elderly patients--do not predict a progressive and rapid loss of beta-cell failure, when associations with high risk genotypes or other islet-cell antibodies are lacking. Patients with LADA share insulin resistance with type 2 diabetic patients, but display a more severe defect in stimulated beta-cell capacity than patients with classical type 2 diabetes. With respect to features of the metabolic syndrome, patients with LADA have lower BMI, blood pressure and triglyceride levels compared with classical type 2 diabetes patients. Early identification of LADA patients will be mandatory, when effective immune interventions are available for prevention of the beta-cell destructive process and insulin requirement of these patients.
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PMID:Progress in the characterization of slowly progressive autoimmune diabetes in adult patients (LADA or type 1.5 diabetes). 1146 May 97

Patients with insulin resistance and/or type 2 diabetes have a 5-fold increase in cardiovascular mortality rate. Therefore, it is a current issue of discussion that arterial hypertension, lipid disorders as well as visceral obesity are coronary risk factors, which might belong to a syndrome that is caused by decreased insulin sensitivity. Concerning a possible molecular link between insulin resistance, atherosclerosis and obesity, we focus in our research on questions looking for a molecular link between lipid metabolism, insulin action, and obesity at a gene regulatory level. Alterations in the structure, function and regulation of transcription factors appear to be such signalling steps which might play an essential role in the pathogenesis and therapy of cardiovascular risk factors associated with insulin resistance, eg the so called metabolic syndrome. Recent examples are members of the nuclear hormone receptor superfamily, eg peroxisome proliferator-activated receptor (PPAR) isoforms and sterol regulatory element-binding proteins (SREBPs). Beside their regulation by different metabolites, these transcription factors are also targets of hormones, like insulin and leptin, growth factors, and inflammatory signals. Therefore, they appear to be a point of signalling convergence at a gene regulatory level. Major signalling pathways coupling receptors at the cell surface for hormones, growth factors as well as cytokines to gene regulatory events in the nucleus are the MAP-kinase cascades. We have recently defined different postreceptor defects in these pathways in patients with clinical phenotypes corresponding to congenital lipoatrophy. Therefore, these studies may identify novel pathways which play a role in the control of body weight, insulin sensitivity and cardiovascular risk.
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PMID:Insulin-regulated transcription factors: molecular link between insulin resistance and cardiovascular risk factors. 1146 84

Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU. m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2). Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs. -84% in control subjects; P = 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P = 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance.
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PMID:Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. 1147 47

Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
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PMID:The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. 1147 13


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