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

The prevention of type 2 diabetes mellitus (DM2) is a major health issue. The DREAM trial is a multinational, multicentre, prospective double-blind study of 5269 patients with an increased risk of developing diabetes. The results show that treatment with rosiglitazone reduces the risk of developing diabetes in this relatively healthy population. The success is achieved at the expense of side effects such as increased weight gain and a higher incidence of non-fatal congestive heart failure. The DREAM trial provides interesting data that may have major implications, but at the same time raises a number of questions that need to be addressed. The ADOPT study shows the benefits of rosiglitazone over glyburide in de novo DM2.
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PMID:[The pharmacological prevention and treatment of diabetes mellitus; significance of 2 recent, large studies for the use of rosiglitazone]. 1755 22

The present article analyses the intimate relationship between diabetes mellitus and congestive heart failure. This relationship is indeed "bidirectional". On the one hand, it is well known that diabetes mellitus, especially type 2 diabetes, predisposes to congestive heart failure due to intricated mechanisms. In most cases, there is a combination of various well-known risk factors, such as obesity, arterial hypertension and coronary heart disease, with a specific diabetic cardiomyopathy, whose pathophysiology is complex. On the other hand, several studies showed that congestive heart failure increases the risk of new type 2 diabetes, probably due to decreased muscular perfusion and excessive neurohumoral response. Remarkably, such a risk could be reduced by a drug capable of inhibiting the renin-angiotensin system, as previously reported in patients with arterial hypertension. The recent launch and the increasing use of thiazolidinediones (glitazones) raise the interest for congestive heart failure in diabetic patients. Indeed, because of their positive effect on insulin resistance and various pleiotropic effects, glitazones may exert some cardiovascular protection; however, both rosiglitazone and pioglitazone are associated with fluid retention, which could reveal or aggravate episodes of congestive heart failure.
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PMID:[Congestive heart failure and diabetes mellitus: an intricated relationship]. 1746 1

Peroxisome proliferator activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. The PPAR subfamily consists of three members: PPARalpha, PPARgamma, and PPARbeta/delta. Fibrates are acting via PPARalpha, and they are used as lipid-lowering agents. PPARgamma agonists reduce insulin resistance and have been used in the treatment of type 2 diabetes. As the knowledge of the pleiotropic effects of these agents advances, further potential indications are being revealed, including a novel role in the management of cardiovascular disorders (CVD). PPARalpha/gamma dual agonists are currently under development and hold considerable promise in the management of type 2 diabetes and provide an effective therapeutic option for treating the multifactorial components of CVD. Several experimental and clinical evidences elucidated the beneficial effects of PPAR ligands in prevention and treatment of various CVD. However, PPARalpha and PPARgamma agonists have been shown to be proinflammatory and proatherogenic in a few studies. Further, PPARgamma ligands have been noted to be involved in the pathogenesis of congestive heart failure. These controversial results obtained from a few studies created further complication in understanding the role of PPARs. The function of PPARdelta and its potential as a cardiovascular therapeutic target are currently under investigation. The present review focuses on the merits and limitations of PPAR agonists with regard to their use in CVD.
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PMID:PPAR ligands: are they potential agents for cardiovascular disorders? 1749 34

Thiazolidinediones (TZDs) have beneficial effects on markers of cardiovascular risk in patients with type 2 diabetes mellitus (DM). This study aimed to investigate the efficacy and safety of low-dose pioglitazone (15 mg per day) in patients with acute myocardial infarction (AMI) and type 2 DM or impaired glucose tolerance (IGT) treated with coronary angioplasty using bare metal stent (BMS). In 56 patients, pioglitazone was orally administered for 6 months after stenting (pioglitazone group). The incidence of in-stent restenosis (ISR) and left ventricular end-diastolic volume index (LVEDVI) at acute phase and 6 months after stenting in these patients were retrospectively compared with those in the other 37 patients (control group) treated without pioglitazone. No adverse events including death, emergency bypass surgery, and reinfarction, occurred in any patients in the hospital. There was no congestive heart failure (CHF) during a follow-up period in the pioglitazone group. At 6 months after stenting, the overall angiographic ISR rate was significantly lower in the pioglitazone group than in the control group (28.6% vs 48.6%, P = 0.049). In patients with hemoglobin A1c (HbA1c) <7.0% at follow-up, the ISR rate was also significantly lower in the pioglitazone group than in controls (21.3% vs 44.8%, P = 0.03). Delta-LVEDVI (defined as follow-up LVEDVI minus acute LVEDVI) was similar between the pioglitazone group and control group (0.13 vs 5.16 ml/m(2), P = 0.482). Low-dose pioglitazone seems to have a potential to reduce ISR and does not adversely affect LV remodeling after AMI treated with coronary angioplasty using BMS in patients with type 2 DM or IGT.
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PMID:Efficacy and safety of low-dose pioglitazone after primary coronary angioplasty with the use of bare metal stent in patients with acute myocardial infarction and with type 2 diabetes mellitus or impaired glucose tolerance. 1753 17

We examined the relation of type 2 diabetes mellitus to parkinsonian signs in older persons. Participants were 1030 women and men (mean age 80.3 y, education 14.5 y, Mini-Mental State Examination 27.9) without dementia or Parkinson disease, enrolled in the Rush Memory and Aging Project, an epidemiologic study of aging. We used separate linear and logistic regression models, adjusted for age, sex, and education, to examine the relation of diabetes, identified by history and medication inspection, to each of the scores of global parkinsonian signs and 4 separate parkinsonian signs. Diabetes was present in 140 (14%) participants. Most participants had mild parkinsonian signs. Diabetes was associated with a more severe global parkinsonian signs score (beta=0.20, SE=0.10, P=0.05) and postural reflex impairment-gait disturbance (beta=0.40, SE=0.17, P=0.02), but not with bradykinesia, rigidity, or tremor. Associations were no longer significant after controlling for vascular risk factors or conditions, particularly body mass index and congestive heart failure. Overall, there was no evidence that vascular variables modified the relation of diabetes to parkinsonian signs. In summary, we found that diabetes was associated with parkinsonian signs, especially postural reflex impairment-gait disturbance, and that vascular factors may play a role in this association.
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PMID:Diabetes and parkinsonian signs in older persons. 1754 40

Obesity and overweight, as a part of the metabolic syndrome, are well known risk factors for the development of diabetes, hypertension, coronary heart disease, hyperlipidemia, stroke, sleep apnea syndrome, osteoarthritis and certain forms of cancer. Cardiovascular disease remains the leading killer in industrialized countries, where it accounts for 40% of deaths. Obesity is defined either by increased waist circumference, waist to hip ratio, or body mass index. Obesity results from an interaction of genes and lifestyle. As people in both developed and developing countries eat more and more energy dense food, and have ever less physical activity, the number of overweight and obese people increases to epidemic proportions. Abdominal obesity plays a key role in the pathophysiology of metabolic disorders, is associated with insulin resistance, and predicts the development of type 2 diabetes and subsequent coronary artery disease. In the general population, obesity is associated with an increased mortality, but paradoxically, a positive correlation between body mass index and survival in congestive heart failure has been reported. In secondary prevention, obesity is underrecognized, underdiagnosed and undertreated in persons with cardiovascular diseases. Weight loss and prevention of weight gain have to be considered one of the most important strategies to reduce the incidence of cardiovascular disease. Increased physical activity and appropriate diet are the cornestones of treatment. Considering the high prevalence of overweight and obesity in Croatia, there is urgent necessity to improve the level of knowledge and skills in understanding obesity by health care services, and to implement appropriate professional strategy to achieve the desired lifestyle modifications.
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PMID:[Obesity--a global public health problem]. 1758 71

Urotensin II is a potent vasoconstrictive peptide that mediates both endothelium-independent vasoconstriction and endothelium-dependent vasodilatation. Its plasma level correlates positively with body weight and is raised in diabetes, renal failure, hypertension, and other cardiovascular diseases including congestive heart failure and carotid atherosclerosis. It can inhibit glucose-induced insulin secretion, and genetic variants in urotensin II gene are associated with insulin resistance and type 2 diabetes. Urotensin II also affects lipid metabolism in fish and food intake in mice. Recent studies have also demonstrated a role of urotensin II in inflammation and endothelial dysfunction. These findings suggest a close relationship between urotensin II and at least some components of the metabolic syndrome, including hypertension, insulin resistance, hyperglycemia, and inflammation.
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PMID:The role of urotensin II in the metabolic syndrome. 1761 Sep 98

Thiazolidinediones (TZDs) or glitazones are agents that are widely used for the treatment of type 2 diabetes mellitus. These drugs have a multitude of therapeutic effects including reduction in insulin resistance and hyperglycaemia, anti-inflammatory effects and amelioration of hypertension, microalbuminuria and hepatic steatosis. The TZD molecular target, peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear transcription factor, is expressed diffusely in humans, including many tissues comprising the cardiovascular and renal systems. This suggests a potential for TZDs to elicit perturbing effects on these systems, which are independent of their effects on glucose and lipid metabolism. One of the most common adverse effects of TZDs is fluid retention, which can result in, or exacerbate, oedema and congestive heart failure (CHF). The frequency of peripheral oedema is approximately 5% when TZDs are used in mono- or combination oral therapy, and about 15% when used with insulin. Patients with type 2 diabetes are at high risk of myriad morbid complications, including CHF. The development of CHF, particularly in the elderly, is a harbinger of premature mortality. TZD-induced oedema is largely peripheral, may have its origins in changes in haemodynamics, with some contribution from molecules, which regulate cell and tissue permeability (e.g. vascular endothelial growth factor and protein kinase Cbeta), and remains the preponderant manifestation of TZD-induced fluid retention even in those with existing heart failure. Preclinical and pilot clinical data attest to the fact that at least part of the fluid retention derives from a direct effect of TZDs on sodium reabsorption via the renal medullary collecting duct, a mechanism that is sensitive to diuretic agents that have this nephron segment as their site of action, in whole or in part (spironolactone, amiloride and hydrochlorothiazide). Our review suggests various potential clinical strategies by which TZD-induced fluid retention might be effectively monitored and addressed.
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PMID:Thiazolidinediones and their fluid-related adverse effects: facts, fiction and putative management strategies. 1772 67

Thiazolidinediones (TZDs) are used as insulin sensitizers in the treatment of type 2 diabetes, but are associated with an increased risk of congestive heart failure (CHF). The odds ratio of ICC was 1.43 (pioglitazone vs placebo) in diabetic patients with high cardiovascular risk in the PROactive trial while it averaged 1.22 (rosiglitazone vs metformin) and 2.20 (rosiglitazone vs metformin) in the ADOPT study. In the interim analysis of the ongoing RECORD trial, the odds ratio averaged 2.15 (rosiglitazone vs metformin or sulfonylureas). In four real life registries, the relative risk of CHF with TZDs varied between 1.06 and 1.76 (between 1.10 and 1.44 combined with insulin) as compared to a treatment without TZDs. Such higher CHF risk should be appreciated according to the potential benefits of glitazones in the management of type 2 diabetes.
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PMID:[Glitazones and congestive heart failure: update on PROactive, ADOPT, DREAM and RECORD clinical trials]. 1789 61

We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From what can be gathered from the very few studies on the UPS in diabetic cardiovascular diseases published so far, the system seems to be functionally active to a different extent in the initiation, progression, and complication stage of atherosclerosis in the diabetic people. Further evidence for this theory, however, has to be given, for instance by specifically targeted antagonism of the UPS. Nonetheless, this hypothesis may help us understand why diverse therapeutic interventions, which have in common the ability to reduce ubiquitin-proteasome activity, can impede or delay the onset of diabetes and cardiovascular diseases (CVD). People with type 2 diabetes are disproportionately affected by CVD, compared with those without diabetes 1. The prevalence, incidence, and mortality from all forms of CVD (myocardial infarction, cerebro-vascular disease and congestive heart failure) are strikingly increased in persons with diabetes compared with those withoutdiabetes 2. Furthermore, diabetic patients have not benefited by the advances in the management of obesity, dyslipidemia, and hypertension that have resulted in a decrease in mortality for coronary heart disease (CHD) patients without diabetes 3. Nevertheless, these risk factors do not fully explain the excess risk for CHD associated with diabetes 45. Thus, the determinants of progression of atherosclerosis in persons with diabetes must be elucidated. Beyond the major risk factors, several studies have demonstrated that such factors, strictly related to diabetes, as insulin-resistance, post-prandial hyperglycemia and chronic hyperglycemia play a role in the atherosclerotic process and may require intervention 67. Moreover, it is important to recognize that these risk factors frequently "cluster" inindividual patients and possibly interact with each other, favouring the atherosclerosis progression toward plaque instability. Thus, a fundamental question is, "which is the common soil hypothesis that may unifying the burden of all these factors on atherosclerosis of diabetic patients? Because evidences suggest that insulin-resistance, diabetes and CHD share in common a deregulation of ubiquitin-proteasome system (UPS), the major pathway for nonlysosomal intracellular protein degradation in eucaryotic cells 89, in this review ubiquitin-proteasome deregulation is proposed as the common persistent pathogenic factor mediating the initial stage of the atherosclerosis as well as the progression to complicated plaque in diabetic patients.
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PMID:The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes. 1797 Dec 5


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