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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the aorta of prediabetic non-obese diabetic mice, a model of human type 1 diabetes, we investigated gene expression of the endothelin receptors and contractility to big endothelin-1 and endothelin-1 at the ages of 10 and 16 weeks. A subgroup of 10- week-old animals was treated with the endothelin ETA receptor antagonist LU461314 (30 mg/kg per day for 6 weeks). Blood glucose levels were normal in all animals. Real-time polymerase chain reaction analysis revealed that vascular ETB receptor expression was higher in 10-week-old non-obese diabetic (NOD) mice compared with controls. In 16-week-old NOD mice, but not in control mice, ETB receptor mRNA was twofold lower (P < 0.05 vs 10-week-old NOD mice). In all groups ETA receptor expression was unaffected by age or treatment. Contractions to big endothelin-1 and endothelin-1 were lower in 10-week-old NOD mice compared with controls. Treatment with LU461314 increased ETB receptor expression in 16-week-old NOD mice, but had no effect on vascular contractility. These data indicate that dysregulation of ETB receptor expression and a decreased contractile response to big endothelin-1 and endothelin-1 are present in the prediabetic state of a model of human type 1 diabetes. These alterations occur independent of glucose levels. Furthermore, ETA receptor blockade is effective in increasing ETB receptor gene expression, suggesting a potential role for endothelin ETA antagonists in the treatment of type 1 diabetes.
J Cardiovasc Pharmacol 2004 Nov
PMID:Upregulation of vascular ET(B) receptor gene expression after chronic ET(A) receptor blockade in prediabetic NOD mice. 1583 54

Cardiomyopathy is a major cause of mortality for both type 1 and 2 diabetic patients. However, experimental analysis of diabetic cardiomyopathy has focused on type 1 diabetes and there are few reports on cardiomyocyte dysfunction in the widely used type 2 diabetic model, db/db. In the current study, we assessed function in isolated ventricular myocytes from type 1 diabetic OVE26 mice and from type 2 diabetic db/db mice. When compared with their respective control strains, both diabetic models showed significant impairment in contractility, as assessed by percent peak shortening, maximal rate of contraction, and maximal rate of relaxation. The calcium decay rate was also significantly reduced in both types of diabetes, but the decrement was much greater in OVE26 myocytes, approx 50% vs only 20% in db/db myocytes. To understand the basis for slow calcium decay in diabetic myocytes and to understand the molecular basis for the quantitative difference between calcium decay in OVE26 and db/db myocytes, we measured cardiac content of the SERCA2a calcium pump. SERCA2a was significantly decreased in OVE26 diabetic myocytes but not reduced at all in db/db myocytes. The reduction of SERCA2a in OVE26 myocytes was completely prevented by overexpression of the antioxidant protein metallothionein, confirming that oxidative stress is an important component of diabetic cardiomyopathy. The current results demonstrate that though contractility is impaired in individual myocytes of db/db hearts and deficits are similar to what is seen in a severe model of type 1 diabetes, impairment in calcium reuptake is less severe, probably as a result of maintenance of normal levels of SERCA2a.
Cardiovasc Toxicol 2005
PMID:Cardiomyocyte dysfunction in models of type 1 and type 2 diabetes. 1624 73

Cardiovascular complications, including diabetic cardiomyopathy, are the major cause of fatalities in diabetes. Diabetic cardiomyopathy is expressed in part through fibrosis and left ventricular hypertrophy, increasing myocardial stiffness leading to heart failure. In order to search for curative interventions, precise evaluation of the diabetic heart pathology is extremely important. Magnetic resonance imaging (MRI) is ideally suited for the assessment of heart disorders due to its high resolution, three-dimensional properties and dimensional accuracy. In this study streptozotocin injected Sprague-Dawley rats were used as a model of type 1 diabetes to characterize abnormalities in the diabetic left ventricle (LV). High resolution MRI using a 9.4 T horizontal bore scanner was performed on control and 7 weeks diabetic rats. In the diabetic rats as compared to controls, we found increased LV wall volume to body weight ratio, suggestive of LV hypertrophy; increased LV wall mean pixel intensity, and decreased T2 relaxation time, both suggestive of changes in the diabetic tissue properties, perhaps due to presence of fibrosis which was detected through increase in the collagen fractional area. In addition, changes in the LV cavity area were observed and quantified in post-mortem diabetic hearts indicative of stiffer and less resilient LV myocardial tissue with diabetes. Together the data suggest that LV hypertrophy and fibrosis may be a major factor underlying structural and functional abnormalities in the diabetic heart, and MRI is a valuable tool to non-invasively monitor the pathological changes in diabetic cardiomyopathy.
Int J Cardiovasc Imaging 2006 Feb
PMID:Characterization of alterations in diabetic myocardial tissue using high resolution MRI. 1637 25

The use of lipid-lowering drugs in diabetes is aimed primarily at reducing the large cardiovascular disease (CVD) risk burden experienced by this group of patients. Statin therapy has been shown to be highly efficacious in reducing CVD risk, both in those with and without prior CVD. Therefore, statins are the first-line lipid-lowering therapy in patients with diabetes. Patients with diabetes and established CVD should have low-density lipoprotein cholesterol (LDLC) lowered to at least 2.6 mmol/L (100 mg/dL) and, if possible, to 1.8 mmol/L (70 mg/dL). Those without prior CVD should have LDLC lowered to 2.6 mmol/L. Triglycerides should be kept less than 1.7 mmol/L (150 mg/dL) and high-density lipoprotein cholesterol (HDLC) above 1.15 mmol/L (40 mg/dL) in men and 1.2 mmol/L (46 mg/dL) in women. Additional therapy with fibrates or nicotinic acid may be needed to achieve these goals; the choice is determined by tolerance and side-effect profile. The use of nicotinic acid or fibrates on their own to achieve triglyceride or HDLC levels should be limited to those patients already at or near LDLC goals. Caution is warranted with combination therapy because muscle side effects, in particular, can increase. In type 1 diabetes, CVD risk is high but trial data are sparse. Where there is nephropathy, and where glycemic control is poor, there will often be a need for triglyceride and HDLC raising interventions as above. In the absence of these, lipid profile is often normal and focus should be on reducing CVD risk by statin therapy. If uncertainty about CVD risk status exists, consideration should be given to using CVD imaging modalities to inform intervention choice in younger patients.
Curr Treat Options Cardiovasc Med 2006 Feb
PMID:Treatment of lipid disorders in patients with diabetes. 1640 82

Optimal glycemic control is essential for the prevention of diabetes-related complications, and the intensive insulin regimens that best resemble physiological insulin secretion are most likely to attain it. However, there are many limitations that preclude the early use of insulin by patients with type 2 diabetes or wider implementation of the intensive regimens in type 1 diabetes. More acceptable alternative routes of insulin administration and effective, noninvasive, patient-friendly delivery systems that alleviate the burden of insulin injections have been researched over the years. To date, only pulmonary inhalation of insulin has become a feasible alternative; it has proved to be as effective and well tolerated as the subcutaneously injected regular insulin and it has a pharmacodynamic profile well suited for mealtime insulin therapy. Several pulmonary insulin delivery systems are in different stages of development, and one (Exubera, Nektar Therapeutics/Pfizer Inc.-Sanofi-Aventis Group) has already become clinically available in the United States and Europe for patients with diabetes. Other noninjectable methods of insulin administration are reviewed.
Timely Top Med Cardiovasc Dis 2006 Nov 01
PMID:Noninjectable methods of insulin administration. 1713 35

Accelerated atherosclerosis and microvascular complications are perhaps the leading cause of coronary heart disease, blindness and renal failure, which could account for disabilities and high mortality rates in patients with diabetes. Several mechanisms including endothelial cell damage, platelet activation and aggregation, hypercoagulability, and impaired fibrinolysis are involved in the pathogenesis of thrombogenic diathesis in diabetes. However, the underlying molecular mechanism is not fully elucidated. A recent clinical study, the Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) Research, has revealed that the reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persist for at least several years, despite increasing hyperglycemia. In addition, intensive therapy during the DCCT also reduced the risk of cardiovascular events by about 50 % in type 1 diabetic patients 11 years after the end of the trial. These clinical studies strongly suggest that so-called 'hyperglycemic memory' causes chronic abnormalities in diabetic vessels that are not easily reversed, even by subsequent, relatively good control of blood glucose. Among various biochemical pathways implicated in diabetic vascular complications, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the theory 'hyperglycemic memory'. In this review, we discuss the role of AGEs in thrombogenic abnormalities in diabetes, especially focusing on the deleterious effects of these macroproteins on endothelial cell function, platelet activation and aggregation, coagulation and fibrinolytic systems.
Cardiovasc Hematol Agents Med Chem 2007 Jul
PMID:Advanced glycation end products (AGEs) and cardiovascular disease (CVD) in diabetes. 1763 Sep 50

Despite documented superiority of positron emission tomography over other investigative modalities in the preoperative staging of non-small cell lung cancer, a proportion of patients will have an inaccurate staging of their mediastinal nodes. The aim of this retrospective review is to analyse the clinicopathological factors responsible for inaccurate nodal staging by integrated PET-CT. A total of 100 consecutive patients with histologically proven non-small cell lung cancer underwent staging with PET-CT prior to lung resection. Thirty-three patients, inaccurately staged by PET-CT, were analysed. Univariate analysis identified the following as significant in causing inaccurate nodal staging: history of tuberculosis (P=0.039) and non-insulin dependant diabetes (P=0.014). In multivariate analysis, we have identified the following as independent factors in causing inaccurate staging of mediastinal lymph nodes: rheumatoid arthritis, non-insulin dependent diabetes, history of tuberculosis, presence of atypical adenomatous hyperplasia and pneumonia (P<0.05). The highest rate of inaccuracy in mediastinal nodal staging was in nodal station 4 (11%, P=0.01) followed by station 7 (10%, P=0.02) and station 9 (3.5%, P=0.01). Interpretation of PET-CT staging of the mediastinum in patients with a history of the above should be with caution, as the incidence of false upstaging and down staging in these subgroups is high. Vigilance of such factors may improve the accuracy of PET-CT in staging mediastinal lymph nodes. Histological confirmation should always be sought.
Interact Cardiovasc Thorac Surg 2007 Jun
PMID:Factors causing inaccurate staging of mediastinal nodal involvement in non-small cell lung cancer patients staged by positron emission tomography. 1766 63

During the last few years, the incidence of microvascular complications in diabetes mellitus has rapidly increased as a consequence of both an increase in incidence of type 2 and type 1 diabetes mellitus. The pathogenesis of diabetic microvascular complications is still largely unknown. Among the many hypotheses, a dysfunction in angiogenesis has been suggested as a common origin for retinopathy, nephropathy, and neuropathy. Based on this hypothesis, inhibition of vascular endothelial growth factor (VEGF) has been tested as a potential therapeutic approach to prevent and cure diabetic microvascular complications. Several VEGF inhibitors are currently under evaluation or are approved for the treatment of wet age-related macular degeneration and macular edema. These include inhibitors of intracellular transcription of VEGF (e.g. bevasiranib), inhibitors of extracellular VEGF (e.g. pegaptanib), inhibitors of VEGF receptor expression (e.g. aflibercept [VEGF-TRAP]) and inhibitors of the intracellular signaling cascade activating VEGF (e.g. midostaurin). According to the existing evidence base, although inhibition of VEGF results in a better outcome in the case of diabetic retinopathy and also, despite some discrepant results, in the case of diabetic nephropathy, there is no final confirmation that VEGF inhibition is a valid approach for diabetic neuropathy. The latter complication actually, in line with other chronic neuropathies, seems to improve with stimulation of angiogenesis through increased expression of VEGF.
Am J Cardiovasc Drugs 2007
PMID:The therapeutic potential of VEGF inhibition in diabetic microvascular complications. 1807 6

Short-term mortality risk in young diabetic people is an indicator of quality of care. We assessed this in the Italian incident population-based registry of Turin. The study base included 1210 incident cases (n=677 aged 0-14 years and n=533 aged 15-29 years) with diabetes, onset period 1974-2000 in the Province of Turin, Italy. The relevant timescale for analysis was the time since the onset of diabetes to death, or till 31 December 2003. Standardized mortality ratio (SMR) for all-cause mortality was computed using the Italian population as a standard, by 5 years, age group, sex, and calendar period. Mean attained age of the incident cohort was 29.7 years (range 5.2-49.7 years). During a mean follow-up period of 15.8 years (range 2.0-29.9 years), there were 19 deaths in 15,967. Nine person-years of observation (n=9.5 expected deaths), giving an all-cause mortality rate of 1.19/1000 person-years (95% CI 0.76-1.87) and an SMR of 1.96 (1.25-3.08). In no cases did death occur at the onset of diabetes or in childhood. Out of 19 deaths, 9 were diabetes related (n=6 coma and n=3 end-stage renal disease). In Cox regression analysis, the hazard ratio (HR) was higher in adult-onset than in childhood-onset diabetes (HR=3.90, 95% CI 1.14-13.39), independently of calendar period and gender. (1) Children and young adults with type 1 diabetes experienced a two-fold higher short-term mortality risk than Italian people of similar age and sex and (2) the risk was higher in adult-onset than in childhood-onset diabetes. The quality of diabetes care should be improved to prevent early deaths.
Nutr Metab Cardiovasc Dis 2009 Jun
PMID:Short-term mortality risk in children and young adults with type 1 diabetes: the population-based Registry of the Province of Turin, Italy. 1867 91

Patients with type 2 diabetes are at high risk of cardiovascular disease. Schramm et al. have published a study in which all residents of Denmark aged 30 years or older on 1 January 1997 (approximately 3.3 million individuals) were followed up for 5 years by individual-level linkage of nationwide registers. The study indicated that patients requiring glucose-lowering therapy (oral treatment, insulin, or combined insulin and oral therapy) exhibited a cardiovascular risk comparable to that of nondiabetic individuals with a prior myocardial infarction, irrespective of sex and type of diabetes. In recent AHA and American Diabetes Association guidelines for the primary prevention of cardiovascular disease, all treatment recommendations for patients with type 2 diabetes also apply to those with type 1 diabetes and to both sexes. Epidemiological evidence reported by Schramm et al. is in line with these recommendations.
Nat Clin Pract Cardiovasc Med 2008 Nov
PMID:Diabetes as a 'cardiovascular disease equivalent': implications for treatment. 1879 31


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