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Biomedical subjects

A J Scheen

Publications and source records attributed to A J Scheen.

At least 19 recordsLinked to original sources

Obesity: causes and new treatments.

The prevalence of obesity increases rapidly in developed and developing countries. Obesity results from a cumulative positive energy balance and is favoured by both genetic and environmental factors. Preventing obesity requires a major investment in nutritional and lifestyle education, particularly in children and adolescents.--The pharmacological approach to obesity includes drugs that reduce food intake (noradrenergic and serotoninergic agents), drugs that increase energy expenditure and compounds that affect nutrient partitioning. In all instances, the benefit-to-risk ratio needs to be carefully assessed. In some patients (severe obesity or obesity accompanied by serious high-risk comorbid conditions), gastric surgery (gastric restriction or gastric bypass) should be considered. In our own experience, it is safe and effective.

Energy Metabolism↗

[Pharma-clinics. The drug of the month. Celecoxib (Celebrex)].

Celecoxib (Celebrex, Pharmacia) is a potent and selective inhibitor of the COX-2 isoform of cyclooxygenase which is used as nonsteroidal anti-inflammatory drug (NSAID). Its current indications are osteoarthritis and rheumatoid arthritis. The usual recommended daily dosage of celecoxib is 200 mg (in one or two intakes per day), to be increased up to 400 mg (two intakes per day) if necessary. Its clinical efficacy seems to be similar to that of other NSAIDs. However, its safety profile, especially gastro-intestinal tolerance and perhaps renal safety, is much better because of the COX-2 selectivity.

Anti-Inflammatory Agents, Non-Steroidal↗

[Clinical study of the month. After the storm over central anorectic agents, the "STORM" study of sibutramine].

The results of the "Sibutramine Trial of Obesity Reduction and Maintenance" (STORM) published in the last issue of December 2000 of the Lancet are summarized. This clinical trial (open label for the first 6 months and double blind versus placebo for a further 18 months) demonstrates the positive effect of sibutramine, a new anorectic drug, on long-term weight maintenance after weight loss in obese subjects. The benefit of sibutramine on the cardiovascular risk profile of the obese patient is more particularly discussed.

Appetite Depressants↗

[Clinical study of the month. The CALM study assessing the combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist in the treatment of diabetic nephropathy].

The main objective of the CALM (Candesartan And Lisinopril Microalbuminuria) study is to assess the effect of a dual blockade of the renin-angiotensin system--using both an angiotensin converting enzyme inhibitor (ACE-I) and an angiotensin II type 1 receptor blocker--in patients with type 2 diabetes, high blood pressure and microalbuminuria. The study included 200 patients randomized to receive candesartan 16 mg or lisinopril 20 mg for 12 weeks, followed by 12 weeks of the same monotherapy or a combination treatment. Main outcomes are the reduction of microalbuminuria and blood pressure. All three of the treatments are effective, but the dual blockade is respectively 18%, 8 mmHg and 5 mmHg more effective in reducing microalbuminuria, systolic and diastolic blood pressure. No comparison is made between this "new" association and the more frequently used biotherapy (i.e. ACE-I plus thiazidic diuretic) and therefore its usefulness in regular practice is still to be determined.

Adult↗

[Pharmacy clinics. Medication of the month. Clopidogrel (Plavix)].

Clopidogrel is launched in Belgium by Sanofi-Synthelabo and Bristol-Myers Squibb under the trade name of Plavix. It is a potent and irreversible ADP receptor antagonist that proved to be more effective than aspirin as antiplatelet agent in the multicentre, randomised double-blind CAPRIE study. It is indicated, at a dosage of 75 mg/day, for the reduction of atherosclerotic events including myocardial infarction, ischaemic stroke and vascular death in patients with atherosclerosis manifested by recent stroke, myocardial infarction or established peripheral vascular disease. Furthermore, recent studies demonstrated that the combination of clopidogrel with aspirin is more effective than aspirin alone and better tolerated than the combination ticlopidine-aspirin for the prevention of atherothrombosis after placement of intravascular stents. Ongoing trials are evaluating the efficacy and safety of such clopidogrel-aspirin combination after acute ischaemic coronary events or in patients at very high risk of stroke. Thus the indications of clopidogrel may become even larger in a next future.

Anti-Inflammatory Agents, Non-Steroidal↗

[Hormonal-metabolic adaptations to muscular exercise].

Physical exercise induces numerous metabolic and hormonal changes that may be influenced by various factors, among which the intensity and the duration of the exertion seem to play a major role besides the possible influence of the intake of exogenous substrates. Such modifications are necessary to satisfy the marked increase in energy demand by exercising muscles, while maintaining plasma glucose concentrations within physiological range. The purpose of the present concise review is to analyse the most important fuel-hormonal adaptations observed during short heavy muscular exercise or during prolonged exercise of moderate intensity as well as those observed after physical training in normal subjects.

Adaptation, Physiological↗

[Beneficial effects of physical activity on cardiovascular risk factors].

Numerous observational (epidemiological surveys) or interventional (controlled trials) studies demonstrated that regular physical activity increases insulin sensitivity in normal subjects and decreases insulin resistance in patients with obesity and/or type 2 diabetes. These favourable effects are at least partially linked to a reduction in abdominal fat mass. This results in a significant improvement of lipid profile, with a decrease in the concentrations of total cholesterol, LDL cholesterol and triglycerides, associated with an increase of HDL cholesterol level. Such favourable metabolic effects related to regular physical activity probably explain the better cardiovascular prognosis observed in regularly exercising subjects as compared to sedentary individuals. These observations should motivate any practitioner to promote endurance physical exercise in every subject, especially in individuals at high cardiovascular risk.

Cardiovascular Diseases↗

[Physical exercise for preventing obesity, promoting weight loss and maintaining weight management].

Obesity is a multifactorial disease making difficult the determination of the precise role of one specific factor such as physical activity or sedentary. Nevertheless, numerous arguments, derived from epidemiological observational studies or from randomized controlled interventional trials, support a favourable role of regular physical activity in the control of body weight. Physical activity contributes to prevent the occurrence of weight excess, especially in children or adolescents, to obtain a satisfactory weight loss, in general in combination with reduced-energy diets, and to maintain long-term weight loss. In addition, physical activity improves both the metabolic profile and health of obese subjects.

Clinical Trials as Topic↗

Thiazolidinediones and liver toxicity.

Thiazolidinediones or glitazones specifically target insulin resistance. They have proven efficacy for reducing plasma glucose levels of type 2 diabetic patients treated with diet alone, sulphonylureas, metformin or insulin. In addition, they may be associated to some improvement of cardiovascular risk profile. However, troglitazone, the first compound approved by the FDA in the US, proved to be hepatotoxic and was withdrawn from the market after the report of several dozens of deaths or cases of severe hepatic failure requiring liver transplantation. It remains unclear whether or not hepatotoxicity is a class effect or is related to the unique tocopherol side chain of troglitazone. Rosiglitazone and pioglitazone, two other glitazones, appear to have similar efficacy on blood glucose control of type 2 diabetic patients as compared to troglitazone. In controlled clinical trials, the incidence of significant increases in liver enzyme levels (ALT) was similar with rosiglitazone or pioglitazone as compared to placebo, whereas troglitazone was associated with a threefold greater incidence. In contrast to the numerous case reports of acute liver failure in patients receiving troglitzone, only two cases of severe reversible liver failure have been reported in patients treated with rosiglitazone, with a causal relationship remaining uncertain. Furthermore, no single case of severe hepatotoxicity has been reported yet with pioglitazone. While regular monitoring of liver enzymes is still recommended and more long-term data are desirable, current clinical evidence supports the conclusion that rosiglitazone and pioglitazone do not share the hepatotoxic profile of troglitazone.

Blood Glucose↗

[The insulin sensitivity concept].

Insulin resistance was already suspected in the thirties from clinical observations in diabetic patients, then better appreciated in the early sixties with the development of insulin radioimmunoassay, and finally confirmed in the last 20 years by using various sophisticated methods able to quantify insulin action. First demonstrated in obese and/or type 2 diabetic patients, the diminution of insulin sensitivity may in fact concern a much larger population. The concept of insulin sensitivity gained a considerable importance when Reaven, in 1988, emphasized the role of insulin resistance in different human diseases. The metabolic syndrome or syndrome X is characterized by the association of various cardiovascular risk factors (among which impaired glucose tolerance, arterial hypertension and dyslipidaemias), all closely linked to insulin resistance which is indeed the core of the syndrome. Even if insulin action signalling appears to be rather complex and the mechanisms leading to insulin resistance still largely unknown, it is essential to develop pharmacological or non pharmacological strategies to improve insulin sensitivity for treating insulin-resistant individuals. Such an approach should allow not only to provide a better blood glucose control in patients with type 2 diabetes, but also to improve the cardiovascular prognosis of numerous patients, with or without diabetes mellitus, who have the metabolic syndrome.

Cardiovascular Diseases↗

[Muscular exercise in the diabetic patient].

Muscular exercise is recommended in patients with type 1 or type 2 diabetes mellitus and is part of the overall management, in combination with diet, oral antidiabetic agents and/or insulin. From a pathophysiological point of view, regular physical activity enhances insulin sensitivity, thus contributing to improve blood glucose control and to reduce cardiovascular risk factors associated to diabetes mellitus. From a practical point of view, however, muscular exercise in a diabetic patient requires special caution, in particular careful selection of the type of exercise, respect of metabolic and/or cardiovascular contraindications, and appropriate adjustment of current pharmacological/dietary treatment.

Blood Glucose↗

[Guidelines for good practice of sports activities].

The present closing article summarizes some guidelines for the good practice of physical activities in order to develop and maintain cardiorespiratory and muscular fitness, and flexibility. Advice is given regarding the recommended quantity and quality of exercise in term of intensity, duration and frequency of training with the aim to optimize the risk/benefit ratio for health, in both aerobic endurance and resistance exercises. The crucial role of an appropriate warm-up and cool-down period, which would include flexibility exercises, is also emphasized. Finally, some practical examples illustrate this vademecum of physical activities.

Exercise↗

[Pharma-clinics. Medication of the month. Repaglinide (NovoNorm)].

Repaglinide (NovoNorm) is an antidiabetic oral agent of the new glinide class with insulinotropic activity. Its action on insulin secretion is more rapid and shorter than that of sulphonylurea compounds. Thanks to these properties, repaglinide is able to better control postprandial hyperglycaemia and is associated with a lower risk of delayed hypoglycaemic episodes. It is indicated for the treatment of type 2 (non-insulin-dependent) diabetes mellitus as monotherapy, after diet failure, or in combination with metformin, when the biguanide is insufficient. NovoNorm is commercialized as tablets of 0.5, 1 and 2 mg, to be taken just before each meal. Initial dosis should be 0.5 mg before meal in diabetic patients on diet alone or 1 mg before meal in patients already receiving an hypoglycaemic agent. If necessary, the dosis should be progressively increased, depending on the individual response, up to 4 mg before meal (maximal daily dosage of 16 mg), in order to optimize blood glucose control.

Administration, Oral↗

[Clinical study of the month. Prevention of type 2 diabetes in overweight patients with impaired glucose tolerance: efficiency of lifestyle changes].

The "Finnish Diabetes Prevention Study" is a prospective controlled study recently published in the New England Journal of Medicine which compared the risk of developing type 2 diabetes among 265 high-risk patients treated by changes in lifestyle to that of 257 matched controlled patients. This intervention trial demonstrated that the risk of type 2 diabetes could be reduced by 58% (p < 0.001) after a mean follow-up of 3.2 years with changes in lifestyle of high-risk overweight subjects with impaired glucose tolerance.

Adult↗

[Multidisciplinary management of the obese patient: example from the Obesity Center at the University of Liege].

Obesity is a mulfactorial disease whose prevalence is progressively increasing. Ideally, it requires a multidisciplinary management by medical doctors, dieticians, psychologists and kinetherapists. The new "Centre de l'Obésité" at the University of Liège aims at fulfilling such objectives with: 1) a first outpatient visit including the simultaneous participation of an endocrinologist, a dietician and a psychologist; 2) a structured and individualized programme of physical rehabilitation; 3) an individualized management of obese subjects as in-(hospital) and/or outpatients, using medical and/or surgical approaches; and 4) an opportunity to benefit of other specialized medical advices, if necessary, in order to increase both the efficacy and safety of the treatment. Owing to the increasing importance of obesity and the well-known difficulties to succeed in treating it, general practitioners should consider this new centre as a valuable help rather than a competitive structure for the management of their patients, especially those with severe or morbid obesity.

Counseling↗

[Info-congress. Insulin therapy for preventing type 1 diabetes in high-risk relatives: negative results of the "Diabetes Prevention Trial-Type 1"].

The results of the American multicentre "Diabetes Prevention Trial-Type 1" were presented by J. Skyler during the last congress of the American Diabetes Association in Philadelphia on June 23, 2001. The prophylactic subcutaneous administration of low-dose 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 (> 50% in the next 5 years), selected upon genetic, immunological and metabolic criteria.

Adolescent↗