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A J Scheen

Publications and source records attributed to A J Scheen.

At least 91 records · Page 5Linked to original sources
PubMed2003

[Clinical study of the month. Premature interruption of ASCOT and CARDS clinical trials of cardiovascular prevention with atorvastatin in patients with arterial hypertension or diabetes mellitus: compromise between ethics and statistics in evidence-based medicine ].

The Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA), performed in hypertensive patients with coronary risk and the Collaborative AtoRvastatin Diabetes Study (CARDS), performed in diabetic patients, also at coronary risk, were prematurely stopped, at the special request of the Data Safety Monitoring Board. Indeed, an interim analysis demonstrated the efficacy of atorvastatin, at a daily dosage of 10 mg as compared to placebo, in the prevention of major cardiovascular events, so that it appeared unethical to continue the study until the end. At the glance of these observations, the ethical and statistical aspects of such prevention clinical trials are discussed, in particular when the premature interruption of the ongoing study appears mandatory, with respect of the main rules of evidence-based medicine.

Anticholesteremic Agents↗
PubMed2003

[Medication of the month. Gliclazide modified release (Uni Diamicron)].

Gliclazide modified release that has been recently launched by Servier (Uni Diamicron 30 mg) is a new formulation of gliclazide to be given once daily. The original hydrophilic matrix improves the biodisponsibility of gliclazide and allows a progressive release of the drug that better parallels the 24-hour glycaemic profile of patients with type 2 diabetes mellitus. Such characteristics may explain the rather low risk of hypoglycaemic episodes and the morning administration should contribute to improve patient's compliance. As the common formulation of gliclazide, the modified release formulation is indicated in the treatment of type 2 diabetes, in adult subjects, when diet, exercise and weight loss are insufficient to restore an adequate metabolic control. It may be used alone or in combination with metformin, glitazones, acarbose or insulin, with the same general principles of use as for the classical formulation of gliclazide.

Administration, Oral↗
PubMed2003

[How I explore ... the controversy concerning the role of oral glucose tolerance test in clinical practice].

The oral glucose tolerance test (OGTT) has been widely used for the diagnosis of diabetes mellitus, gestational diabetes or impaired glucose tolerance. However, since 1997, OGTT is not considered anymore as the first choice test for the diagnosis of diabetes mellitus or impaired glucose tolerance, being replaced by fasting glycaemia. Numerous studies, however, stressed the discrepancies between these two diagnostic approaches, so that OGTT still has defenders as a useful tool to diagnose diabetes. Besides, emphasis has been recently put on both postprandial hyperglycaemia, considered as a major cardiovascular risk factor, and impaired glucose tolerance as a predictor of progression toward overt type 2 diabetes, two parameters well addressed by the OGTT. Thus, even if the place to be reserved to the OGTT is controversial, in our opinion, this test still has a place in clinical biology.

Administration, Oral↗
PubMed2003

[Clinical study of the month. The EUROPA study: cardiovascular protection with perindopril in patients with stable coronary heart disease].

The multicentre placebo-controlled double-blind "EUropean trial on Reduction Of cardiac events with Perindopril in patients with stable coronary Artery disease" (EUROPA) assessed whether the angiotensin-converting-enzyme inhibitor perindopril reduces cardiovascular risk in a population with stable coronary heart disease and no apparent heart failure, whatever the associated cardiovascular risk. Patients were randomly assigned perindopril 8 mg once daily (n = 6110) or matching placebo (n = 6108). After a mean follow-up of 4.2 years, a relative risk reduction of 20% (95% CI 9-29, p = 0.0003) was observed in the combined primary endpoint (cardiovascular death, myocardial infarction, or cardiac arrest) in the group treated with perindopril as compared to placebo. About 50 patients needed to be treated for a period of 4 years to prevent one major cardiovascular event. This benefit was consistent in all predefined subgroups. According to these results, treatment with perindopril, on top of other preventive medications, should be considered in all patients with stable coronary heart disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

[How I explore ... the risk of a patient developing type 2 diabetes].

Both the prevalence and the incidence of type 2 diabetes are increasing rapidly. Effective prevention measures, including lifestyle or drug prescription, have been recently reported. It is thus important to detect at risk individuals in order to provide appropriate diet and exercise recommendations or even pharmacological treatment. We summarize the most useful indices based on anamnesis, clinical examination and biological assays that can help to detect subjects at high risk of progression towards type 2 diabetes.

Comorbidity↗
PubMed2002

Results of obesity treatment.

Obesity is a chronic disease so that results of obesity treatment should only be evaluated on a long-term basis. The present paper aims at analyzing the long-term (1 year or more) results of three anti-obesity approaches, i.e. lifestyle modifications, pharmacological treatments and surgical procedures. Dietary interventions include diets with moderate calorie restriction and very-low energy diets (VLED). Even if an initial greater weight loss is observed with VLED, no study has conclusively shown that the long-term approaches including VLED are better than non-VLED programmes. Physical activity is not the most efficient method of initial weight loss, but it appears to be more crucial for maintaining weight loss once it has occurred. In general, long-term results of lifestyle modifications are disappointing because of poor compliance. Several 1-2 year large-scale randomized placebo-controlled clinical trials with orlistat, an intestinal lipase inhibitor, and sibutramine, a central appetite regulator, have demonstrated that both drugs significantly, although modestly on average, increase weight reduction, almost double the number of responders (weight loss >=5 or 10% of initial body weight) and improve weight maintenance up to 2 years. Surgical procedures provide a much greater weight reduction than medical interventions in patients with morbid obesity, particularly after a follow-up of several years. Weight loss is greater with gastric bypass, inducing some malbsorption, than with gastroplasty, a pure gastric restriction technique. Associated risk factors such as markers of insulin resistance syndrome and type 2 diabetes are remarkably reduced, but no prospective study of morbidity or mortality is available yet. In all cases, the management of obesity requires a multidisciplinary approach to improve the success rate.

Humans↗
PubMed2002

[Postprandial hyperglycemia. I. Physiopathology, clinical consequences and dietary management].

Postprandial hyperglycaemia depends on the amount and type of ingested carbohydrates and/or the degree of inhibition of hepatic glucose output following a meal. The kinetics of carbohydrate absorption is directly influenced by the type of food (carbohydrates with variable glycaemic indices, fibre content of the meal) and by the speed of gastric emptying. Hepatic glucose output is remarkably inhibited by insulin and strongly stimulated by glucagon. It remains abnormally high after a meal in diabetic patients because of insufficient portal insulin concentrations, hepatic insulin resistance and/or hyperglucagonaemia. In diabetic patients, postprandial hyperglycaemia contributes to the aggravation of chronic hyperglycaemia, and thus to the increase of glycated haemoglobin levels. Furthermore, it has been recently demonstrated that postprandial hyperglycaemia increases the cardiovascular risk, even in nondiabetic subjects, probably by inducing endothelial dysfunction. Appropriate dietary counselling plays a key-role in the control of postprandial hyperglycaemia. Generally speaking, it includes a selection of carbohydrates with low glycaemic index and a higher fibre intake. Pharmacological interventions may also be considered when necessary.

Absorption↗
PubMed2002

[Postprandial hyperglycemia. II. Pharmacological approaches].

Besides dietary approaches, various pharmacological means have been recently developed in order to better control postprandial hyperglycaemia. This objective may be obtained: 1) by slowing down the intestinal absorption of carbohydrates; 2) by insuring a better insulin priming soon after the meal; and 3) by inhibiting post-prandial glucagon secretion or action. Some hormones (amylin, glucagon-like peptide-1) can slow gastric emptying while alpha-glucosidase inhibitors (acarbose, miglitol) retard intestinal digestion and resorption of complex carbohydrates. A more physiological post-meal profile of insulin may be obtained in type 2 diabetes by using new insulin secretagogues of the glinide family (repaglinide, nateglinide) with an earlier and shorter insulinotropic action or, mainly in type 1 diabetes but also in type 2 diabetes, by using short-acting insulin analogues (lispro. Asp B28) or inhated insulin the action of which is faster than that of subcutaneous insulin. Post-prandial glucagon secretion can be inhibited by amylin. GLP-1 or insulin while other glucagon antagonists are currently in development.

Diabetes Mellitus, Type 1↗
PubMed2002

[Medication of the month. Rosiglitazone (Avandia)].

Rosiglitazone (Avandia, Glaxo-SmithKline) belongs to a new family of oral hypoglycaemic agents, thiazolidinediones or glitazones. These molecules act as selective agonists of nuclear receptors (PPAR gamma) and improve insulin sensitivity. In Belgium as in all European countries, rosiglitazone is indicated for the treatment of type 2 diabetes, only in combination with another antidiabetic oral agent, in patients insufficiently controlled with metformin or a sulphonylurea at a maximal tolerated dose. In these patients, rosiglitazone, at a daily dose of 4 mg (sometimes 8 mg/day with metformin), reduces fasting glycaemia by 2-3 mmol/l and glycated haemoglobin level by about 1%. It exerts also favourable effects on some risk factors related to insulin resistance syndrome, which may contribute to improve cardiovascular prognosis of patients with type 2 diabetes. Hepatic safety of rosiglitazone seems to be good, although it is still recommended to check liver enzymes regularly. As all glitazones, rosiglitazone moderately promotes weight gain. It can also induce some fluid retention which may reveal or aggravate heart failure in at risk patients.

Administration, Oral↗
PubMed2002

[Clinical study of the month. The LIFE study: cardiovascular protection of hypertensive patients by losartan].

The LIFE study ("Losartan Intervention For Endpoint reduction in hypertension study") demonstrated a significant cardiovascular protection by an angiotensin AT1 receptor antagonist, losartan, in hypertensive patients with left ventricular hypertrophy. At similar blood pressure control, losartan, as compared to atenolol, reduced the relative risk of primary cardiovascular event (death, myocardial infarction, or stroke) by 13% (p = 0.021) in the whole cohort of 9.193 patients after a mean follow-up of 4.7 years. In a subgroup of 1.195 diabetic patients, the protection was even more marked with a reduction of the combined risk of 24% (p = 0.031) and a fall of the mortality of 39% (p = 0.002). In conclusion, losartan prevents cardiovascular morbidity and death more effectively than atenolol, and seems to confer benefits beyond reduction in blood pressure.

Aged↗
PubMed2002

[One type of diabetes may conceal another].

The abrupt interruption of insulin therapy in a severely obese diabetic woman submitted to a protein-sparing modified fast in a metabolic ward led to a severe ketoacidosis. This complication occurred because the patient had type 1 rather than type 2 diabetes, and the diagnosis of ketoacidosis was delayed because of confusion between ketonuria resulting from insulin deprivation and ketonuria associated with carbohydrate and energy restriction. This case report illustrates the danger of accepting an apparently obvious diagnosis which might be in fact erroneous. More particularly, it points out the importance of a correct differential diagnosis between C-peptide positive insulin-requiring type 2 diabetes and C-peptide negative (insulin-dependent) type 1 diabetes.

Adult↗
PubMed2002

[Pitfalls and precautions concerning the use of conventional oral antidiabetic drugs].

The main pitfalls regarding the use of sulphonylureas and metformin in type 2 diabetic patients are described and illustrated by a clinical case. Advices are given in order to avoid the occurrence of severe hypoglycaemic episodes with sulphonylureas and to minimise the risk of lactic acidosis with metformin. These drugs, when used appropriately with respect of contra-indications, have an excellent safety profile and remain the basis of the treatment of type 2 diabetes.

Acidosis, Lactic↗
PubMed2002

[Clinical study of the month. Attempt at preservation of B cells during the initial phase of type 1 diabetes: negative results with ultralente insulin, but promising results with an anti-CD3 monoclonal antibody].

Type 1 diabetes is an autoimmune disease leading to a progressive exhaustion of the insulin secretion and a destruction of the B-cells. Attempts of preservation of insulin-producing B-cells can be performed at an early, most often silent, stage of the disease in well-selected at high risk subjects or during the period immediately following the clinical diagnosis based upon classical signs of hyperglycaemia. In the "Diabetes Prevention Trial-Type 1", the prophylactic subcutaneous administration of low-dose ultralente insulin was not able to prevent the development of type 1 diabetes nor to preserve residual insulin secretion in young relatives at very high-risk of diabetes, selected upon genetic, immunological and metabolic criteria. In contrast, a pilot randomized trial shows that a treatment with a nonactivating humanized monoclonal antibody against CD3 mitigates the deterioration in insulin production and improves metabolic control, with lower dose of exogenous insulin, during the first year of type 1 diabetes mellitus in 9 out of 12 treated patients. Besides a better understanding of the natural history of the disease, these clinical trials open new perspectives for prevention of type 1 diabetes mellitus, currently assessed by the Belgian Diabetes Registry.

Adult↗
PubMed2002

[Prevention of type II diabetes by inhibiting the renin-angiotensin system].

Type 2 diabetes mellitus and arterial hypertension are part of the insulin resistance syndrome. Besides a metabolic component, insulin resistance has also an haemodynamic component, especially in relation with an endothelial dysfunction. Some studies suggested that inhibitors of angiotensin converting enzyme can improve insulin sensitivity. Interestingly enough, three clinical trials recently reported concordant results showing that the inhibition of the renin-angiotensin system significantly reduces the risk of developing type 2 diabetes in patients at high risk of vascular complications, essentially with hypertension: the CAPPP trial with captopril (-14%, p = 0.39), the HOPE study with ramipril (-34%, p < 0.001) and the LIFE study with losartan (-25%, p < 0.001). However, these observations could be criticized because such a protective effect was only considered as a secondary endpoint in these studies. Two large prospective, controlled, randomized, double-blind trials are ongoing to specifically confirm this interesting hypothesis, one with ramipril and the other with valsartan.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

[Clinical study of the month. The LIPS study: fluvastatin for prevention of cardiac events following percutaneous coronary angioplasty].

The prospective placebo-controlled LIPS study ("Lescol Intervention Prevention Study") demonstrated a significant cardiovascular protection by fluvastatin in patients with coronary artery disease (stable or unstable angina, silent ischemia), without major hypercholesterolaemia (135-270 mg/dl) following successful completion of their first percutaneous coronary intervention. When compared to the placebo group (n = 833), the fluvastatin group (n = 844) showed a relative risk reduction by 22% (relative risk: 0.78; 95% confidence interval: 0.64-0.95; p = 0.01) of major adverse cardiac events after a median time of follow-up of 3.9 years. This effect is observed independently of baseline total cholesterol, of the presence of diabetes mellitus or the existence of multivessel disease. These results suggest that fluvastatin may favorably influence the restenosis process after percutaneous coronary intervention, even in the absence of severe hypercholesterolaemia.

Adolescent↗
PubMed2002

[Smoking, insulin resistance and type 2 diabetes].

Smoking is a major risk factor for cardiovascular disease. It is associated with endothelial dysfunction and lipid disorders similar to those found in the insulin resistance syndrome. Studies have thus tried to demonstrate a relationship between smoking and insulin resistance, and between smoking and type 2 diabetes mellitus. Even if their results may sometimes differ, smoking does seem to be associated with an impaired insulin sensitivity that is proportional to tobacco consumption. Nicotine replacement therapies seem also to generate a certain, though lower, degree of insulin resistance. If there is no major weight gain after smoking cessation, the latter is accompanied by a progressive return to normal insulin sensitivity. Several large epidemiological studies recently demonstrated that smoking could increase the risk of type 2 diabetes mellitus, with a relative risk between 1.5 and 3.0. Finally, among type 2 diabetic patients, smoking has a harmful effect on metabolic control and long-term complications of the disease, at least partially by increasing the components of the insulin resistance syndrome. All these observations represent further argument to promote smoking cessation in the general population, and more particularly in individuals at risk to develop type 2 diabetes, as well as in the diabetic population.

Cardiovascular Diseases↗