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

Diabetes is strongly associated with coronary, cerebral and peripheral arterial disease, as well as with microangiopathy. In those with diabetes, the extent of macrovascular disease increases and atherosclerotic plaques are more prone to rupture. Both hormonal abnormalities (insulin resistance that is typically present for many years before the onset of type 2 diabetes) and metabolic abnormalities contribute. Multi-targeted intensive therapy is imperative; however, unfortunately it is underutilized. Functional and structural derangements contribute to impaired arterial and ventricular compliance predisposing to congestive heart failure that is increasingly recognized to be a cause of morbidity and mortality in patients with diabetes.
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PMID:Cardiovascular complications in diabetes mellitus. 1578 Aug 22

A progressive chain of pathophysiological events links cardiovascular risk factors to clinical manifestations of disease and life-threatening cardiovascular events. This chain--the cardiovascular continuum--underlies cardiovascular disease and holds the key to its prevention and treatment. Progressive tissue damage can result in morbidity from congestive heart failure, end-stage heart disease, nephrotic proteinuria and dementia and, eventually, death from cardio- or cerebrovascular causes. The renin-angiotensin-aldosterone system (RAAS) is involved at all stages of the cardiovascular continuum, because the effector molecules of the RAAS, angiotensin II in particular, have direct pathobiological effects on a variety of tissues, including the endothelium, vascular smooth muscle and the renal mesangium. Clinical trials of angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors have demonstrated the essential validity of this hypothesis. Interruption of the RAAS has been shown to reduce cardiovascular morbidity and mortality in patients with left ventricular hypertrophy, heart failure and post-myocardial infarction, as well as renal disease in patients with type 2 diabetes. Key questions remain, however. What are the clinical effects of combination ARB and ACE inhibitor treatment? How will combinations of RAAS blockade with other agents, such as statins, affect the cardiovascular continuum? Answers to these questions will require well-planned, adequately powered clinical trials, such as the Programme of Research tO evaluate Telmisartan End-organ proteCTION (PROTECTION) and the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programmes. However, it is already clear that RAAS blockade is an essential part of blocking progression along the cardiovascular continuum.
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PMID:The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. 1582 52

The major challenge for the treatment of hypertensive patients with type 2 diabetes is to achieve the uniformly recommended blood pressure goal of 130/80 mmHg, and 120/75 mmHg in proteinuric patients. Such low target blood pressure levels require the administration of multiple drugs. Angiotensin receptor blockers and the combination of angiotensin receptor blockers with diuretics fulfil the criteria to lower blood pressure effectively with a placebo-like side-effect profile. Beyond pressure control, clinical prospective trials have documented that it does matter what kind of antihypertensive agent is used to control blood pressure. Large-scale follow-up trials have documented blood pressure independent effects of angiotensin receptor blocker on cardiac [left-ventricular hypertrophy (LVH), congestive heart failure] and renal protection (proteinuria, chronic renal failure). Of note, in these trials, angiotensin receptor blockers have been combined with diuretics, and most of the included patients have been on combination therapy comprising two to four antihypertensive agents. In addition to the combination of an angiotensin receptor blocker with a diuretic, the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor appeared to be most effective in reducing proteinuria, attenuating chronic renal failure and treating congestive heart failure.
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PMID:Optimizing therapeutic strategies to achieve renal and cardiovascular risk reduction in diabetic patients with angiotensin receptor blockers. 1583 71

A patient with a history of type II diabetes mellitus (DM), end stage renal disease (ESRD), and congestive heart failure (CHF) developed necrotizing fasciitis caused by Serratia marcescens after scraping his leg on rocks in a river while fishing. Aggressive management with surgical debridement, antibiotics, and pressure support was unsuccessful.
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PMID:A fatal case of necrotizing fasciitis caused by Serratia marcescens. 1586 38

Endothelins are powerful vasoconstrictor peptides that also play numerous other functions in many different organs. Endothelin-1 (ET-1) is the most abundant and important of this family of peptides in blood vessels. Production of ET-1 is increased in the endothelium and the kidney in salt-dependent models of hypertension (e.g.: DOCA-salt rats and Dahl salt-sensitive rats, in salt-loaded SHR-SP, in angiotensin II-infused and in diabetic rats). ET-1 elicits an inflammatory response by increasing oxidant stress in the vascular wall, which induces vascular remodeling and endothelial dysfunction found in the hypertensive models that exhibit an endothelin-mediated component. Endothelin receptor antagonism reduces blood pressure and vascular hypertrophic remodeling present in these hypertensive models. Patients with stage 2 hypertension have enhanced vascular expression of ET-1. Endothelin receptor antagonists lower blood pressure in hypertensive patients. They could become therapeutic agents for prevention of target organ damage in hypertension and in type 2 diabetes, chronic renal failure and congestive heart failure. Side effects of endothelin receptor blockers have prevented up to the present their development for these indications. New endothelin antagonists devoid of these side effects, or alternatively inhibitors of the endothelin converting enzymes that generate ET-1 may in the future become available to block the endothelin system. However, to date endothelin antagonists have been approved only for the treatment of primary pulmonary hypertension, a rapidly fatal condition in which the endothelin system plays an important role and endothelin antagonists exert favorable effects.
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PMID:Vascular endothelin in hypertension. 1595 45

Type 2 diabetes mellitus is a public health problem of epidemic proportions and its prevalence is on the rise. The typical American born today has a one in three chance of developing type 2 diabetes. This diagnosis is associated with an adverse cardiovascular prognosis and is considered the risk equivalent of established coronary disease. Many risk factors, including the metabolic syndrome, have been implicated in its development. Even in high-risk individuals, type 2 diabetes is a preventable disease. Diet and exercise have been consistently shown to decrease the incidence of diabetes in large randomized controlled studies. Additionally, new-onset diabetes was reduced by several oral pharmacologic anti-diabetic agents including metformin, acarbose and troglitazone in randomized trials which studied patients with impaired glucose tolerance. More interestingly, multiple large prospective studies have also reported a reduction in the development of type 2 diabetes in patients treated with anti-hypertensive agents, predominantly angiotensin converting enzyme inhibitors and angiotensin receptor blockers. In this review, we will discuss some of these important trials and the speculative mechanisms whereby those medications prevent type 2 diabetes. Such observations, if proven to be true, may represent preventive strategies which can be considered in patients with pre-diabetic conditions such as the metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure or other risks for the development of type 2 diabetes.
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PMID:Strategies to prevent type 2 diabetes. 1600 80

Pioglitazone is an insulin-sensitizer with a thiazolidinedione structure. It is used to reduce hyperglycemia and is frequently prescribed to type 2 diabetic patients. However, it causes edema as an adverse effect in some patients. Although the mechanism of edema is unclear, it may bring an increased risk of congestive heart failure. We investigated whether pioglitazone correlates with the level of plasma human atrial natriuretic peptide (hANP), a marker for congestive heart failure. We administered 15 mg/day of pioglitazone for 3 months to 49 patients (34 men and 15 women; mean age: 64+/-12 years) with type 2 diabetes and no history of pretibial edema. Three of the patients complained of pretibial edema during the 3-month period, and their plasma hANP levels were higher than those of the other 46 before and during the treatment. We therefore suspect that pretibial edema appearing after administration of low-doses of pioglitazone coincides with the level of plasma hANP, and that the appearance of pretibial edema may reflect an increase in circulating blood volume induced by pioglitazone.
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PMID:Relationship between plasma hANP level and pretibial edema by pioglitazone treatment. 1600 33

This paper aims at comparing two meta-analyses of clinical trials having investigated the effect of the inhibition of the renin-angiotensin system either with an angiotensin converting enzyme inhibitor (ACEI) or with a selective angiotensin receptor blocker (ARB) on the incidence of new cases of type 2 diabetes mellitus in subjects with arterial hypertension or with congestive heart failure. The protection appears similar with ACEIs in six trials in a total of 24.623 patients (hazard ratio: 0.77; CI 95% 0.72-0.81; p < 0.00001 and with ARBs in five trials in a total of 14.344 patients (hazard ratio: 0.79; CI 95% 0.73-0.85; p < 0.00001). It is consistent whatever the comparator, a thiazide diuretic agent, a beta-blocker, a dihydropyridine calcium channel blocker or a placebo. The large ongoing ONTARGET controlled study will allow a direct comparison between an ACEI, ramipril, and an ARB, telmisartan, and will also investigate the potential benefit of a combined treatment with both drugs. The inhibition of the renin-angiotensin system should be considered among pharmacological strategies of prevention of type 2 diabetes mellitus.
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PMID:[Similar reduction in new cases of type 2 diabetes with angiotensin receptor blocker and ACE inhibitor: comparison of meta-analyses of prospective randomised trials]. 1603 5

The range of therapeutic modalities to treat type 2 diabetes mellitus has broadened in recent years. Biguanides and thiazolidinediones are the two currently available classes of anti-hyperglycemic agents with insulin-sensitizing properties. Thiazolidinediones, in particular, have received much attention, not only for the well documented hepatotoxicity of troglitazone that led to its removal from the market in 2000, but also for the emerging data that support the beneficial effects of the thiazolidinedione class of drugs on beta-cell rejuvenation and cardiovascular risk reduction. In the US, thiazolidinediones are indicated either as monotherapy or in combination with a sulfonylurea, metformin, or insulin in cases where diet, exercise, and a single drug fail. In contrast, the UK National Institute for Clinical Excellence included in its re-appraisal of 'glitazones' in August 2003 the continued exclusion from licensed use in the UK of combination therapy with thiazolidinediones and insulin. When added to insulin therapy, thiazolidinediones appear to effectively lower glucose levels and reduce insulin dosage in clinical trials involving individuals with poorly controlled type 2 diabetes. However, weight gain, hypoglycemia, and fluid retention pose problems in certain patients. The fluid retention may exacerbate or even precipitate congestive heart failure, which usually necessitates discontinuation of the drug. Risk stratification and careful management of patients at risk for heart failure, including those taking insulin concomitantly, allow healthcare providers to safely administer combination therapy with thiazolidinediones in patients with type 2 diabetes. Hepatic toxicity with currently available thiazolidinediones has been found to be minimal overall.
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PMID:Thiazolidinediones and insulin: rationale for use and role of combination therapy in type 2 diabetes mellitus. 1605 38

The thiazolidinediones have been in clinical use for the management of type 2 diabetes for the past five years. These agents reduce insulin resistance by acting as ligands that regulate gene expression related to the proliferation and differentiation of adipose tissue. Overall, data from several clinical studies suggest that their hypoglycaemic efficacy is slightly less than sulphonylureas and metformin but greater than acarbose and the glinides. In the short term, treatment with thiazolidinediones is associated with weight gain, expansion of plasma volume, fluid retention, peripheral oedema, an increased risk of congestive heart failure when combined with insulin, and an idiosyncratic hepatotoxic reaction to troglitazone. The long term consequences of these effects are not known. Contrary to expectations, despite being insulin sensitisers these agents do not favourably influence the other components of the metabolic syndrome that are believed to be aggravated by insulin resistance. Dyslipidaemia and elevated blood pressure, which are major risk factors of cardiovascular disease in type 2 diabetes, are not favourably improved with thiazolidinedione treatment. Unlike the sulphonylureas and metformin, which have been shown in recent long term randomised studies to reduce cardiovascular risk substantially, there is no data on the long term cardiovascular safety of the thiazolidinediones. At present, in the absence of long term data, the thiazolidinediones in clinical use are moderately effective hypoglycaemic drugs with no particular advantage over existing treatments in type 2 diabetes.
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PMID:Thiazolidinediones in type 2 diabetes--have they lived up to expectations? 1622 62


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