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Biomedical subjects

A J Scheen

Publications and source records attributed to A J Scheen.

At least 217 records · Page 12Linked to original sources

[Arterial hypertension and type 2 diabetes].

Diabetes mellitus is frequently associated with arterial hypertension and the combination of both entities markedly increases the vascular risk. In type 2 diabetes, hypertension appears very early, especially in the presence of obesity, is part of the insulin resistance syndrome, and contributes to high cardiovascular morbidity and mortality rates in this population. Appropriate regulation of blood pressure is crucial in order to reduce not only microangiopathy (nephropathy and retinopathy) but also macroangiopathy (coronary heart disease and stroke) in hypertensive type 2 diabetic patients. Target blood pressure values have been decreased in recent years and should be < 130/85 mmHg, and may be even lower according to recent data. The optimal modalities of pharmacological treatment remain controversial, but obviously several medications are required to reach such objectives in most hypertensive patients with type 2 diabetes.

Angiography↗

[Info-Congress. The HOPE Study: Demonstration of the cardiovascular protection of ramipril, an ACE-inhibitor].

The results of the HOPE ("Heart Outcomes Prevention Evaluation") study were presented at the XXIst Congress of the European Society of Cardiology in Barcelona (August 28-September 1, 1999). In addition, results obtained in the large diabetic sub-population (38% of the 9541 patients included in the trial) were reported at the XXXVth Congress of the European Association for the Study of Diabetes in Brussels (September 28-October 2, 1999). The HOPE trial was terminated early because of a reduction of the relative risk (-22%, p < 0.000002) of major cardiovascular events in the group treated with ramipiril compared to the group receiving placebo. Such a favourable effect of ramipril was observed in non-diabetic subjects in secondary prevention and in diabetic patients in secondary or primary prevention. In the latter population, a significant reduction in the incidence of microangiopathic complications (nephropathy and retinopathy) was also demonstrated.

Angiotensin-Converting Enzyme Inhibitors↗

[Benefits and limitations of protein diets in obese patients with type 2 diabetes].

Weight excess plays a major role in the pathophysiology of type 2 diabetes but only a minority of patients succeed in following a restrictive calorie diet in the long-term, able to reduce body weight and maintain normoglycaemia. Very low-calorie diets such as protein diets rapidly reduce plasma glucose levels by various mechanisms, among which a significant improvement of hepatic and muscular insulin sensitivity and a partial recovery of insulin secretion. The rapidity of the hypoglycaemic action suggests that calorie restriction plays a more important role than weight loss itself. The lowering of plasma glucose levels imposes an early reduction in the doses of antidiabetic agents to avoid hypoglycaemia. Well-balanced protein diets are well tolerated, provided that they are restricted to a few weeks. The most important limitation of the protein diet is the risk of weight regain afterwards and such situation requires the maintenance of an hypocaloric diet in the long-term. Ideally, the protein diet should be integrated in a global approach including treatment of obesity, type 2 diabetes and frequently associated other risk factors.

Blood Glucose↗

[Medication compliance].

Compliance is defined as the extent to which a patient's behaviour coincides with medical or health advice. Medication compliance seems to be rather low as 30 to 60% of no or poor adherence to medical recommendation have been reported. Numerous factors may influence medication compliance among which patient's characteristics, disease particularities, drug treatment modalities or physician's attitudes. The consequences of medication non-compliance may not only be dangerous for patient's health, but also dramatically increase the financial cost for public health services. Thus, all energies should be devoted to improve drug compliance, including treatment optimization and simplification, patient's information and education, use of practical means that facilitate adherence to medical recommendation, the patient being responsible for his/her treatment.

Drug Therapy↗

[How I assess ... home glycemic control in diabetic patients].

Self blood glucose monitoring is now a key element in the management of diabetic patients. However, in order to improve overall blood glucose control, self-monitoring should lead to self-management. This implies that the patient modifies his/her behaviour (diet, exercise, oral antidiabetic agents, insulin doses) to ameliorate the metabolic status according to his/her blood glucose measurements. While the place of home blood glucose monitoring is rather well defined in type 1 diabetes, it remains more controversial in type 2 diabetes.

Blood Glucose Self-Monitoring↗

[Clinical study of the month. Does chronic sleep deprivation predispose to metabolic syndrome?].

According to a recent experimental study published in the Lancet, sleep debt, frequently imposed by the life habits of industrialized countries, results in profound metabolic (impaired glucose tolerance) and endocrine (increased sympathetic activity and evening cortisol levels) alterations, which mimic those of normal ageing and may have pathophysiological consequences in the long term. Another study recently published in the International Journal of Obesity demonstrated a significant positive relationship between the duration of shift-work and body mass index or waist to hip ratio, a marker of visceral adiposity. One may thus hypothesize that chronic sleep deprivation could predispose to the metabolic syndrome and increase the cardiovascular risk.

Aging↗

[Therapeutic non-compliance: a major problem in the prevention of cardiovascular diseases].

The prevention of cardiovascular diseases relies upon the correction of risk factors and, more particularly, the optimal management of various metabolic abnormalities such as obesity, dyslipidaemias, diabetes mellitus and arterial hypertension. Such an approach first requires the adherence to life-style habits (healthy diet, physical activity and no smoking) and, in case of failure, the use of lipid-lowering drugs, antidiabetic agents and/or antihypertensive medications. Sometimes, a monotherapy may be sufficient but, in most cases, a drug combination is mandatory because of the need to reach tight therapeutic targets and of the presence of a polypathology, especially within the frame of the metabolic syndrome. Unfortunately, all surveys indicate that therapeutic compliance to non-pharmacological advice and even to drug prescriptions is far from being excellent. Such a non-compliance limits the efficacy of the prevention strategies and contributes to markedly increase the cost of metabolic diseases and associated complications.

Antihypertensive Agents↗

[Thiazolidinediones].

Explore the source record for details and available documents.

Chemical and Drug Induced Liver Injury↗

The postprandial state and risk of cardiovascular disease.

Metabolism in man is regulated by complex hormonal signals and substrate interactions, and for many years the clinical focus has centred on the metabolic and hormonal picture after an overnight fast. More recently, the postprandial state, i.e. 'the period that comprises and follows a meal', has received more attention. The oral glucose tolerance test (OGTT), although highly non-physiological, has been used largely as a model of the postprandial state. Epidemiological studies have shown that, when 'impaired', oral glucose tolerance is associated with an increased risk of cardiovascular disease. Postprandial hyperlipidaemia has been investigated more recently in epidemiological, mechanistical and intervention studies, most of which indicate that high postprandial triglyceride levels, and particularly postprandial rich triglyceride remnants, constitute an increased risk for cardiovascular disease. Recent studies have shown that excessive postprandial glucose excursions are accompanied by oxidative stress and, less well known, activation of blood coagulation (increase in circulating D-dimers and prothrombin fragments). The mechanisms through which increased postprandial glucose levels and lipid concentrations may damage endothelial cells on blood vessel walls appear to be complex. These mechanisms include the activation of protein kinase C, increased expression of adhesion molecules, increased adhesion and uptake of leucocytes, increased production of proliferative substances such as endothelin, increased proliferation of endothelial cells, increased synthesis of collagen IV and fibronectin, and decreased production of nitric oxide (NO). In conclusion, the 'postprandial state' cumulatively covers almost half of the nycthemeral period, and its physiology involves numerous finely regulated motor, secretory, hormonal and metabolic events. Epidemiological and mechanistical studies have suggested that perturbations of the postprandial state are involved in cardiovascular disease. Correcting the abnormalities of the postprandial state must form part of the strategy for the prevention and management of cardiovascular diseases, particularly those that are associated with diabetes mellitus.

Blood Coagulation↗

Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty.

OBJECTIVE: To examine the factors associated with liver steatosis in severely obese subjects and to test the potential reversibility of fatty liver after weight loss. DESIGN: Retrospective clinical study. SUBJECT: 528 obese patients before bariatric surgery and 69 obese subjects of the initial cohort evaluated before and 27+/-15 months after gastroplasty. MEASUREMENTS: Fatty deposition (scored as mild, moderate or severe) and inflammatory changes were evaluated in liver biopsies; clinical (body mass index (BMI), age, gender, duration of obesity) and biological (glucose, triglycerides, liver enzymes) parameters were related to histological findings. RESULTS: 74% of the 528 biopsies showed fatty change, estimated as mild in 41% of cases, moderate in 32% and severe in 27%. The prevalence of steatosis was significantly higher in men than in women (91% vs 70%, P = 0.001) and in patients with impaired glucose tolerance or type 2 diabetes compared with nondiabetics (89% vs 69% P = 0.001). The severity of the steatosis was associated with BMI (P = 0.002) but not with the duration of obesity or the age of the patient. When compared with patients without fatty change, those with liver steatosis had significantly higher fasting plasma glucose (5.5 mmol/l vs 5.1 mmol/l, P = 0.007) and triglycerides (1.8 mmol/l vs 1.3 mmol/l, P = 0.002). Mean serum liver enzyme activities (alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl-transpeptidase (gammaGT) were significantly (P < 0.001) increased in patients with fatty change but remained within laboratory reference values. In the 69 patients who have been evaluated after a marked weight reduction (-32+/-19kg), 45% of the biopsies were considered as normal (vs 13% before, P < 0.001) while pure fatty change was still observed in 38% of the patients (vs 83% before, P = 0.001). However, the severity of the steatosis was significantly (P < 0.001) reduced (mild: 62% vs 21%; moderate: 23% vs 37%; severe: 15% vs 42%). In addition, a significant increase of hepatitis was observed in 26% of the biopsies (vs 14% before, P < 0.05). CONCLUSIONS: Liver steatosis in obese subjects is associated with men, diabetic status, BMI, higher fasting glucose and hypertriglyceridaemia. Postgastroplasty weight loss reduces liver steatosis, but seems to increase the incidence of inflammatory lobular hepatitis.

Adult↗

Effects of exercise on neuroendocrine secretions and glucose regulation at different times of day.

To study the effects of time of day on neuroendocrine and metabolic responses to exercise, body temperature, plasma glucose, insulin secretion rates (ISR), and plasma cortisol, growth hormone (GH) and thyrotropin (TSH) were measured in young men, both at bed rest and during a 3-h exercise period (40-60% maximal O2 uptake). Exercise was performed at three times of day characterized by marked differences in cortisol levels, i.e., early morning (n = 5), afternoon (n = 8), and around midnight (n = 9). The subjects were kept awake and fasted, but they received a constant glucose infusion to avoid hypoglycemia. Exercise-induced elevations of temperature were higher in the early morning than at other times of day. The exercise-induced glucose decrease was approximately 50% greater around midnight, when cortisol was minimal and not stimulated by exercise, than in the afternoon or early morning (P < 0.05). This effect of time of day appeared unrelated to decreases in ISR or increases in temperature and GH. Robust TSH increases occurred in all exercise periods and were maximal at night. The results demonstrate the existence of circadian variations in neuroendocrine and metabolic responses to exercise.

Adult↗

The roles of time of day and sleep quality in modulating glucose regulation: clinical implications.

Consistent variations in glucose regulation across the 24-hour cycle are present in normal subjects. These diurnal variations are altered in various states of impaired glucose tolerance (aging, obesity, diabetes). Changes in insulin secretion, clearance and/or action across the day have been demonstrated. Studies in subjects receiving continuous intravenous glucose infusion have shown that major alterations of glucose tolerance occur during sleep and that sleep quality markedly influences glucose utilization. Diurnal variations in glucose tolerance result from the alternation of wake and sleep states as well as from intrinsic effects of circadian rhythmicity. The important roles of physiological variations in levels of counterregulatory hormones which are markedly dependent on sleep (i.e. growth hormone) or circadian rhythmicity (i.e. cortisol) have only begun to be appreciated. The modulatory effects of sleep and circadian rhythmicity on glucose regulation may have important clinical implications for the diagnosis and treatment of abnormalities of carbohydrate metabolism.

Circadian Rhythm↗

Oral antidiabetic agents. A guide to selection.

Type 2 diabetes mellitus (formerly named non-insulin-dependent diabetes mellitus or NIDDM) is a heterogeneous disease resulting from a dynamic interaction between defects in insulin secretion and insulin action. Various pharmacological approaches can be used to improve glucose homeostasis via different modes of action: sulphonylureas essentially stimulate insulin secretion, biguanides (metformin) act by promoting glucose utilisation and reducing hepatic-glucose production, alpha-glucosidase inhibitors (acarbose) slow down carbohydrate absorption from the gut and thiazolidinediones (troglitazone) enhance cellular insulin action on glucose and lipid metabolism. These pharmacological treatments may be used individually for certain types of patients, or may be combined in a stepwise fashion to provide more ideal glycaemic control for most patients. Selection of oral antihyperglycaemic agents as first-line drug or combined therapy should be based on both the pharmacological properties of the compounds (efficacy and safety, profile) and the clinical characteristics of the patient (stage of disease, bodyweight, etc.). Mildly hyperglycaemic patients should preferably be treated with metformin, acarbose or thiazolidinediones (which are not associated with any hypoglycaemic risk), while more severely hyperglycaemic individuals should receive a sulphonylurea. In moderately hyperglycaemic patients, sulphonylureas should be preferred in nonobese patients while metformin, and probably also thiazolidinediones, should have priority in obese insulin-resistant type 2 diabetic patients. Acarbose is mainly indicated to reduce post-prandial glucose fluctuations and improve glycaemic stability. Each antihyperglycaemic agent may also be combined with insulin therapy to improve glycaemic control and/or reduce the insulin requirement of diabetic patients after secondary failure to oral treatment. Finally, safety should be taken into account in elderly patients and/or those with renal impairment, especially as far as the use of sulphonylureas (higher risk of hypoglycaemia) and metformin (higher risk of lactic acidosis) is concerned.

Administration, Oral↗

[Drug clinics. Clinical drug trials: the importance and role of the general practitioner].

Clinical trials are an essential step in the development of a drug. They must be conducted according to strict rules called "Good Clinical Practice" or GCP. GCP requirements aim to guarantee a perfect methodology in the planning, realization and interpretation of clinical trials. The latter can be divided in four phases: phase 1 aiming to demonstrate the safety and to investigate the pharmacokinetics/metabolism of the drug in healthy volunteers; phase 2 aiming to study the intrinsic activity (generally versus a placebo) and safety of the compound in a rather small number of (hospitalized) patients; phase 3 aiming to confirm the comparative efficacy (versus a placebo or a reference drug) and safety of the pharmacological agent in a quite large number of (ambulatory) patients; and phase 4 carried out after commercialization, to verify the clinical utility of the drug in conditions of daily practice. Because he/she occupies a crucial position in the recruitment and follow-up of outpatients, the general practitioner should play a more active role in clinical trials, provided that he/she could work in collaboration with academic centers specialized in clinical pharmacology which can help to perform studies in accordance with GCP requirements.

Academic Medical Centers↗

[Syndrome X, at the crossroads of metabolic and cardiovascular diseases].

The relationships between metabolic disorders and cardiovascular diseases are very strong. Hypercholesterolaemia and diabetes mellitus, for instance, are well-known risk factors. The multifaceted metabolic syndrome or syndrome X, originally described by Reaven in 1988, comprises several abnormalities which are associated to insulin resistance and compensatory hyperinsulinaemia. Syndrome X results in an increased vascular risk by at least two mechanisms. On the one hand, it favours atherosclerosis and is associated to angiographic lesions, especially in the coronary arteries. On the other hand, it is associated to endothelial dysfunction which may contribute to myocardial ischaemia even in presence of angiographically normal arteries, a phenomenon named also syndrome X by the cardiologists. Thus, metabolic syndrome X and cardiological syndrome X are very close and syndrome X may be considered as a crossing between metabolic disorders and cardiovascular diseases.

Arteriosclerosis↗

[Drug clinics. The drug of the month. Ranitidine bismuth citrate (Pylorid)].

Ranitidine bismuth citrate (Pylorid, Glaxo-Wellcome) is a novel salt of ranitidine which provides a unique combination of properties: inhibition of secretion of gastric acid by competitive antagonism of the action of histamine at the histamine H2-receptor on the gastric parietal cell, mucosal protective effects and anti-Helicobacter pylori action. Ranitidine bismuth citrate provides effective healing and symptom relief, both in duodenal ulcer disease and in gastric ulcer disease. When coprescribed with certain antibiotics (clarithromycin alone or combined with amoxicillin or nitro-imidazole), it heals ulcers, eradicates Helicobacter pylori and prevents recurrence of the disease. Several clinical studies demonstrated that ranitidine bismuth citrate is well-tolerated and has quite similar efficacy as proton pump inhibitors.

Amoxicillin↗