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Query: UMLS:C0011849 (diabetes)
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The frequency of arterial hypertension occurrence in polish population amounts to 30-40%, among diabetics is significantly higher-70%. According to the WHO/ISH Guidelines all hypertensive patients with diabetes are included into the "high risk group" independent of hypertension stage. Pharmacological treatment of hypertension is this group of patients has a particular meaning. Among hypertensive patients the degree of blood pressure lowering is more effective for cardiovascular risk reduction than choice of drug. This fact is well documented in clinical trials comparing antihypertensive efficacy of old and new antihypertensive drugs (for example UKPDS, STOP 2, INSIGHT). From the other point of view renal protection and metabolic benefits, as well as reduction of target organ damage are more advantageous for angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and calcium antagonists than for diuretics and beta-blockers. Despite fast progress in clinical research on new antihypertensive drugs (especially AT1 receptor inhibitors) ACE-I seem to still remain still the "first choice" for hypertensive diabetics. Adequate blood pressure control among diabetic hypertensives is of special importance and usually needs appropriate combined antihypertensive therapy. Our review presents detailed information about treatment advantages and disadvantages of drugs from different antihypertensive classes in light of current clinical trials and international guidelines.
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PMID:[Antihypertensive treatment for patients with hypertension and diabetes type II--current clinical research]. 1293 58

Diabetes mellitus type 2 develops worldwide in the dimensions of an epidemic disease. In order to reduce the personal burden of patients and the enormous costs for the health system, which are mainly due to diabetes complications, diabetes prevention is urgently needed. Regarding pathophysiology, type 2 diabetes develops on the basis of insulin resistance, together with increasing reduction of insulin secretion. This leads to postprandial blood glucose peaks (Impaired Glucose Tolerance, IGT), which furthermore increase insulin resistance (metabolic resistance) and decrease insulin secretion, finally resulting in manifestation of diabetes mellitus. Therefore it is a logical way of diabetes prevention, to treat postprandial blood glucose peaks in the early stadium of IGT. The STOP-NIDDM trial showed conclusively that acarbose reduces postprandial hyperglycemia and diabetes incidence for 36% in comparison to placebo in a group of IGT patients. At the same time the incidence of normal glucose tolerance increased significantly for 30%. The NNT ("number needed to treat") for acarbose to avoid one case of diabetes manifestation in patients with IGT, is eleven patients in 3.3 years. The preventive effect of acarbose is independent of age, gender or weight of the patients. So acarbose has the potential to reduce postprandial hyperglycemia, which is the driving force for diabetes, and thus can prevent diabetes mellitus type 2.
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PMID:[Postprandial blood glucose as the driving force in pathogenesis of type 2 diabetes]. 1469 35

An impaired glucose tolerance results in a significantly increased cardiovascular risk. In view of the dramatically increasing population with non-insulin-dependent diabetes mellitus, metabolic syndrome and impaired glucose tolerance, new therapeutic options are urgently required. In the past, studies of an intensified diabetes therapy generally did not reveal a relevant effect on the incidence of macrovascular complications. Consequently, the phrase of the "glucose paradoxon" was coined. The STOP-NIDDM study (study to prevent non-insulin-dependent diabetes mellitus) for the first time showed a reduction of cardiovascular events by 49% in patients with impaired glucose tolerance treated with acarbose compared with placebo. Furthermore, a retrospective metaanalysis of seven placebo-controlled long-term-studies of acarbose in patients with non-insulin-dependent diabetes mellitus showed a reduction of cardiovascular events by 41% (p = 0.0017). In summary, there is good evidence from placebo-controlled studies of a significant reduction of cardiovascular risk by acarbose in patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus.
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PMID:[Does targeted therapy of type 2 diabetes prevent cardiovascular incidents?]. 1469 36

Type 2 diabetes mellitus is a major health problem associated with excess morbidity and mortality. Defects in the action and/or secretion of insulin are the two major abnormalities leading to development of glucose intolerance. Any intervention in the impaired glucose tolerance phase that reduces resistance to insulin or protects the beta-cells, or both, should prevent or delay progression to diabetes. The natural history of type 2 diabetes includes a preceding period of impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) which provides an opportunity for targeted intervention within large communities. As the prevalence of this metabolic disorder is rapidly increasing and current treatment fails to stabilise the disease in most patients, prevention should be considered as a key objective in the near future. Lifestyle intervention studies have consistently shown that quite modest changes can reduce the progression from IGT to diabetes by 50-60%. The Diabetes Prevention Program (DPP) randomised trial has shown that a combined program of weight loss, improvement of diet and increase of physical exercise lowers the risk for development of type 2 diabetes by 58% compared with placebo. It may, however, not be possible to translate these successful findings to larger cohorts or maintain the lifestyle changes longer term. This has lead to consideration of pharmacotherapy. Benefits have been found for metformin, acarbose and troglitazone. Treatment with metformin was less effective than lifestyle modifications, resulting in an average reduction of risk for development of type 2 diabetes by 31% compared with placebo. Similarly, acarbose in the STOP-NIDDM trial reduced the risk of developing type 2 diabetes in patients with IGT by 25%. Remarkably, cardiovascular event rates, in particular myocardial infarction, were significantly reduced when acarbose was used instead of placebo in subjects with glucose intolerance. The ACE inhibitors captopril (CAPPP) or ramipril (HOPE) and the Angiotensin-II receptor antagonist losartan (LIFE) have been shown to reduce the appearance of diabetes by one third when given to patients with hypertension. Since many hypertensive patients are insulin-resistant and have an increased risk in developing type 2 diabetes, the protective effect of these classes of antihypertensive drugs might be explained by their antiinsulin-resistance effects.
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PMID:[Progress in the prevention of type 2 diabetes]. 1474 78

The STOP-NIDDM Trial has shown that acarbose treatment in subjects with impaired glucose tolerance is associated with a significant risk reduction in the development of diabetes, hypertension and cardiovascular complications. Kaiser and Sawicki have accused the investigators of the STOP-NIDDM Trial of major biases in the conduct of the study, of manipulating the data and of conflict of interest. The aim of this paper is to present data and explanations refuting these allegations. In the STOP-NIDDM Trial, 61 subjects were excluded from the efficacy analysis before unblinding for legitimate reasons: failure to satisfy major entry criteria (n=17) and lack of post-randomisation data (n=44). Blinding and randomisation were carried out by an independent biostatistician. Titration of placebo/acarbose is well described in the protocol and in the study design paper. Of the study population, 9.3% had a fasting plasma glucose of > or =7.0 mmol/l at screening and could have been diabetic according to the new diagnostic criteria. However, even if these subjects are excluded, patients having acarbose treatment still saw a significant risk reduction in the development of diabetes (p=0.0027). The changes in weight are consistent in different publications and are related to different times of follow-up and assessment. Weight change does have an effect on the development of diabetes, but acarbose treatment is still effective even after adjusting for this (p=0.0063). The cardiovascular endpoints were a clearly designated assessment in the original protocol, and only those defined in the protocol and ascertained by the independent Cardiovascular Event Adjudication Committee were used in the analysis. Hypertension was defined according to the most recent diagnostic criteria. The STOP-NIDDM Trial results are scientifically sound and credible. The investigators stand strongly behind these results demonstrating that acarbose treatment is associated with a delay in the development of diabetes, hypertension and cardiovascular complications in a high-risk population with IGT.
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PMID:Acarbose for the prevention of Type 2 diabetes, hypertension and cardiovascular disease in subjects with impaired glucose tolerance: facts and interpretations concerning the critical analysis of the STOP-NIDDM Trial data. 1515 Jun 89

The increasing incidence of type 2 diabetes constitutes a considerable individual and socio-economic risk, therefore preventive concepts are urgently needed. Three prospective studies show that a "life-style-intervention" as well as drugs can prevent the development of diabetes as well as cardiovascular complications: The Diabetes Prevention Study (DPS) evaluated the influence of a "life-style-intervention". The Diabetes Prevention Program (DPP) additionally examined the effect of metformin. In the STOP-NIDDM-Study acarbose was used for diabetes prevention and cardiovascular endpoints were also evaluated. The incidence of type 2 diabetes can be significantly reduced by a "life-style-intervention" and also by the administration of metformin or acarbose. With acarbose cardiovascular events are reduced significantly and comparably to a therapy with statins in primary prevention.
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PMID:[Primary prevention of diabetes mellitus type 2]. 1524 4

Diabetes is a cardiovascular disease, however, up to two decades ago there was no evidence that hyperglycemia itself is an independent risk factor. However consistent data from recently published prospective studies in subjects with impaired glucose tolerance and patients with early type 2 diabetes prove that postprandial/postchallenge hyperglycemia is an important risk factor for cardiovascular disease. Pathophysiological investigations have shown that excessive postprandial hyperglycemia causes a cascade of proatherogenic abnormalities such as oxidative stress, activation of NFkappaB receptor and impaired NO release of the endothelium. Moreover in the last years intervention studies like DIGAMI and a study in critical ill patients have shown that strict normalization of blood glucose control improves life expectancy in seriously ill patients. There are now three studies: STOP-NIDDM, MERIA and IMT study of the common carotid arteries which impressively demonstrate that control of postprandial hyperglycemia may prevent cardiovascular complications to the same degree as reported for statins and AC-inhibitors. Thus control of the glucose trias-HbA(1c), postprandial and fasting plasma glucoses is essentially practice in patients with cardiovascular disease.
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PMID:[Postprandial hyperglycemia as a risk factor for cardiovascular disease. Therapy improves prognosis]. 1534 Jul 33

In the recent years there has been increasing interest in the effects of oral hypoglycemic drugs on the cardiovascular system. This has arisen because of recognitions that thiazolidine-diones, peroxisome proliferators-activated receptor gamma (PPAR-gamma), may have antiatherogenic actions and that sulphonylureas are capable of closing the ATP-dependent potassium channel. PPAR-gamma agonists exert antiatherogenic action by inhibition the production of monocyte inflammatory cytokines, inhibition of expression of adhesion molecules in endothelial cells, inhibition of the proliferation of vascular smooth muscle cells and have antioxidative effects. The United Kingdom Prospective Diabetes Study (UKPDS), published in 1998, found that the use of sulphonylureas had no increase in cardiovascular mortality and that metformin therapy in obese individuals with type 2 diabetes mellitus was associated with reduced cardiovascular death. Recently, the STOP-NIDDM trial has been shown that patients with impaired glucose tolerance treated with the alpha-glucosidase inhibitor acarbose had a significant reduction in the risk of cardiovascular disease. Currently, the results of the UKPDS trial are the only available clinical data on which to base the choice of treatment for type 2 diabetic patients. When a glucose-lowering oral drug is considered necessary and is not contraindicated, the firstline choice is a sulphonylurea or a glinide (repaglinide or nateglinide) for diabetics who are not overweight and metformin for those who are.
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PMID:[Cardiovascular effects of oral hypoglycemie drugs]. 1534 Jul 37

Heterozygous coding mutations in the melanocortin 4 receptor gene (MC4R) are the most common genetic causes of severe human obesity identified to date. To determine whether MC4R has a role in causing severe obesity in Pima Indians, we sequenced the coding region of this gene in 426 full-heritage, non-first-degree related, adult Pima Indians (300 severely obese and 126 nondiabetic nonobese control subjects). Three coding variations were detected as heterozygotes only in severely obese subjects. One variation, detected in three obese subjects, was a novel single-base insertion (A) at nucleotide 100, and it predicted a frameshift and premature STOP at codon 37. The second variant, detected in 10 obese subjects, predicted a previously identified arginine-to-glutamine substitution at codon 165, and the third variant, detected in one obese subject, predicted a novel glycine-to-serine substitution at codon 231. Three polymorphisms were also identified in the 5' untranslated region, but these variants were detected in both obese and lean subjects and had similar allele frequencies. We conclude that variations in MC4R may account for a small portion of obesity in Pima Indians, but they do not explain the overall high prevalence of obesity in this Native American population.
Diabetes 2004 Oct
PMID:Melanocortin 4 receptor gene variation is associated with severe obesity in Pima Indians. 1544 3

Protective effects of the alpha-glucosidase inhibitor acarbose have been reported for various diabetic complications. In the STOP-NIDDM study, even patients without overt diabetes, but with impaired glucose tolerance, had a reduction in cardiovascular events when treated with acarbose. Therefore, we investigated the effect of repetitive postprandial hyperglycemia on the cardiac ischemia/reperfusion injury in vivo. Mice were treated daily by single applications of placebo, sucrose (4 g/kg body weight), or sucrose + acarbose (10 mg/kg body weight) by gavage for 7 days. Acarbose treatment significantly reduced the sucrose-induced increase in plasma glucose concentration. Subsequently, animals underwent 30 min of ischemia by coronary artery ligation and 24 h of reperfusion in vivo. In the sucrose group, ischemia/reperfusion damage was significantly increased (infarct/area at risk, placebo vs. sucrose, 38.8+/-7.5% vs. 62.2+/-4.8%, P<0.05). This was prevented by acarbose treatment (infarct/area at risk 30.7+/-7.2%). While myocardial inflammation was similar in all groups, oxidative stress as indicated by a significant increase in lipid peroxides was enhanced in the sucrose, but not in the sucrose + acarbose group. In summary, repetitive postprandial hyperglycemia increases ischemia/reperfusion damage. This effect can be prevented by treatment with the alpha-glucosidase inhibitor acarbose.
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PMID:Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury: prevention by the alpha-glucosidase inhibitor acarbose. 1567 Nov 53


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