Search PubMed⌕ Search

Biomedical subjects

A J Scheen

Publications and source records attributed to A J Scheen.

At least 37 records · Page 2Linked to original sources
PubMed2006

[DREAM study: prevention of type 2 diabetes with ramipril and/or rosiglitazone in persons with dysglycaemia but no cardiovascular desease].

DREAM ("Diabetes Reduction Assessment with ramipril and rosiglitazone Medication") is a double-blind randomised placebo-controlled clinical trial with a 2-by-2 factorial design aiming to study the effects of an ACE inhibitor (ramipril 15 mg/day) and/or a thiazolidinedione (rosiglitazone 8 mg/day) on the development of diabetes or death (primary outcome) and on the regression to normoglycaemia (secondary outcome) in 5269 adults aged 30 years or more with impaired fasting glucose and/or impaired glucose tolerance, and no previous cardiovascular disease. There was no statistical evidence of an interaction between the ramipril and the rosiglitazone arms. After a mean follow up of 3 years, the use of ramipril does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycaemia. In contrast, the treatment with rosiglitazone reduces by almost 60% the incidence of type 2 diabetes and increases the likelihood (+70%) of regression to normoglycaemia. Whether it is a true prevention effect or simply a treatment effect remains to be determined when participants will be retested after a washout period. Cardiovascular event rates were rather low and much the same in all treatment groups, except a higher rate of heart failure in the rosiglitazone group. These results suggest that the routine inhibition of the renin-angiotensin system for the express purpose of preventing diabetes is not indicated in individuals not at high risk for cardiovascular disease and appear to confirm the promises of the glitazone use in the very early stage of the natural history of type 2 diabetes.

Adult↗
PubMed2005

[Triple oral therapy in type 2 diabetes].

Type 2 diabetes has a complex pathophysiology, combining a defect of insulin secretion by the pancreas, an increased glucose production by the liver and a reduced insulin-mediated glucose uptake by the skeletal muscle. Each of these abnormalities can be partially reversed by a specific drug, an agent promoting insulin secretion (sulphonylurea or glinide), metformin and a thiazolidinedione (glitazone), respectively. Therefore, a triple oral therapy, targeting simultaneously the three main metabolic abnormalities of type 2 diabetes, deserves special attention. Recent clinical trials have shown both the efficacy and safety of this triple oral therapy. However, its precise place remains to be better specified in the overall management of type 2 diabetes.

Administration, Oral↗
PubMed2005

[Which indications for statins besides their cholesterol-lowering effect?].

Statins are essential drugs for the prevention of coronary and cerebral vascular complications. Besides their specific cholesterol-lowering effect, these agents exert various pleiotropic effects, which probably contribute to the cardiovascular protection, but may also play a favourable effect in various other pathologies. Some recent data suggested that statins may play a positive effect in the prevention of Alzheimer disease and colorectal cancer. In contrast, after some initial hope, recent observations in the field of osteoporosis prevention provided discordant and finally rather disappointing results. New prospective studies are mandatory before accepting such new potential indications of statins.

Alzheimer Disease↗
PubMed2005

Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion?

Elderly people are more glucose intolerant and insulin resistant than young individuals, and many of them will develop type 2 diabetes. It remains, however, controversial whether this decrease in function is due to an inevitable consequence of "biological aging" or due to environmental or lifestyle variables. Indeed, increased adiposity/altered fat distribution, decreased fat free mass/abnormal muscle composition, poor dietary habits and physical inactivity all contribute to reduce insulin sensitivity. Insulin resistance in elderly people appears to predominate in skeletal muscle, whereas hepatic glucose output seems to be almost unaffected. Several abnormalities in islet beta-cell and insulin secretion were also pointed out in elderly people such as increased amyloid deposition and decreased amylin secretion, impaired insulin secretion pulsatility, decreased insulin sensitivity of pancreatic beta-cells to insulinotropic gut hormones and diminished insulin response to non-glucose stimuli such as arginine. Controversial results were reported concerning the effects of aging on absolute insulin secretion in response to oral or intravenous glucose. However, insulin secretion appears to decrease with age, with significantly diminished beta-cell sensitivity and acute insulin response to glucose, provided it is analyzed relative to concomitant decreased insulin sensitivity. Thus, there is an interplay between decreased insulin secretion and increased insulin resistance that largely explains the abnormal glucose metabolism seen in elderly. Weight loss, especially reduction of abdominal adiposity, and increased physical activity may contribute to improve insulin sensitivity and glucose tolerance, and prevent the development of type 2 diabetes in elderly people.

Adipose Tissue↗
PubMed2005

[PPAR-gamma receptors, new therapeutic target in metabolic and cardiovascular diseases].

PPARs ("Peroxisome Proliferator-Activated Receptors") belong to a superfamily of nuclear receptors with several isoforms, among which PPAR-alpha mainly located in the liver and PPAR-gamma mainly located in the adipose tissue. These receptors are considered as major pharmacological targets since the discovery of their activation by specific agonists, which lead to various favourable metabolic effects. Improvement of lipid profile by fibrates is explained by the activation of liver PPAR-alpha receptors. However, PPAR-gamma receptors have focused most fundamental and clinical research in recent years after the demonstration of their activation by thiazolidinediones (pioglitazone, rosiglitazone), a new class of antidiabetic agents. Beyond their effects on insulin sensitivity, glitazones exert pleiotropic effects that may result in cardiovascular protection in high risk patients. It has been recently demonstrated that certain angiotensin AT1 receptor blockers (sartans) can also exert a partial agonist activity on PPAR-gamma. Among the molecules of this class, telmisartan appears to exert this effect at the lower concentrations. Thus, PPAR-y, as common pharmacological target, may, at least partially, explain some of the effects observed with both thiazolidinediones and inhibitors of the renin-angiotensin system, in particular the improvement in insulin sensitivity (in particular via an increase in adiponectin levels), the protection against type 2 diabetes, the reduction in arterial blood pressure and the prevention of cardiovascular complications. There is currently a major interest from the pharmaceutical industry in the development of new molecules able to activate both PPAR-alpha and PPAR-gamma.

Cardiovascular Diseases↗
PubMed2005

[Bariatric surgery: 10-year results of the Swedish Obese Subjects Study].

The 10-year results of the prospective, controlled Swedish Obese Subjects Study were recently reported in the New England Journal of Medicine by L. Sjöström and colleagues. This trial compared obese subjects who underwent gastric surgery and contemporaneously matched, conventionally treated obese control subjects. The follow-up rate for laboratory examinations was 74.5 percent at 10 years. At that time, data of 627 patients of the control group (mean age of 48 years, body mass index of 41 kg/m2) were compared to those of 641 patients who were submitted to surgery (banding n = 156, vertical banded gastroplasty n = 451 and gastric bypass n =34). At 10 years, the body weight had increased by 1.6 percent in the control group and decreased by 16.1 percent in the surgery group (p < 0.001), and similar changes were observed for waist circumference (+2.8 percent versus -10.1 percent, respectively, p < 0.001). Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period. Ten-year rates of recovery from diabetes, hypertriglyceridaemia, low levels of high-density lipoprotein cholesterol, hypertension, and hyperuricaemia were more favourable in the surgery than in the control group. The surgery group had lower 10-year incidence rates of diabetes, hypertriglyceridaemia, and hyperuricaemia (but not of hypertension) than the control group. In conclusion, as compared with conventional therapy, bariatric surgery appears to be a valuable option for the treatment of severe obesity, resulting in long-term weight loss, improved lifestyle, and, except for hypercholesterolaemia that was not significantly affected, amelioration in cardiovascular risk factors that were elevated at baseline. Obtaining long-term data concerning the effect of weight loss on overall mortality and on the incidence rates of myocardial infarction, stroke, and cancer remains a key-objective of this landmark study.

Adult↗
PubMed2005

["Treating to New Targets": plea for a LDL cholesterol target of or below 75 mg/dl in any patient with coronary heart disease].

The "Treating to New Targets" (TNT) trial compared atorvastatin 80 mg (aiming at reducing LDL cholesterol < or = 75 mg/dl) and atorvastatin 10 mg (LDL < or = 100 mg/dl as target) in 10,001 patients with stable coronary heart disease followed up for 5 years. A reduction of major cardiovascular events of 22% was observed in the atorvastatin 80 mg group as compared to the atorvastatin 10 mg group (hazard ratio: 0.78; 95 % interval of confidence: 0.69-0.89; p < 0.001). Such clinical efficacy was obtained while a good drug safety profile was maintained. Total mortality was not significantly different between the two groups. However, and remarkably, cardiovascular death was not the first cause of death anymore in this atorvastatin-treated population. The results of TNT in patients with stable coronary heart disease thus confirm the results of PROVE-IT in patients with acute coronary syndrome. These two randomised controlled trials should encourage considering a LDL cholesterol level of 75 mg/dl (rather than 100 mg/dl) as a new target in any patient with coronary heart disease.

Adult↗
PubMed2005

[Insulin detemir (Levemir)].

Insulin detemir (Levemir) is a soluble long acting human insulin analogue acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to reversibly bind to albumin, thereby providing slow absorption and a prolonged metabolic effect (up to 24 hours) with low variability. Indeed, in patients with type 1 or type 2 diabetes mellitus, insulin detemir has a more predictable, protracted and consistent effect, with less intrapatient variability in glycaemic control (particularly fasting plasma glucose levels), compared with NPH (Neutral Protamine Hagedorn) insulin. Insulin detemir, is at least as effective as NPH insulin in maintaining overall glycaemic control, with a lower risk of nocturnal hypoglycaemia. It also provides the additional benefit of less body weight gain as compared to other basal insulins. Levemir, presented in cartridges for the pen device NovoPen 3 and administered preferably at bedtime (if necessary morning and evening), is a promising new option for basal insulin therapy in diabetic patients, especially those on a basal-bolus scheme.

Diabetes Mellitus↗
PubMed2005

[Proactive study: secondary cardiovascular prevention with pioglitazione in type 2 diabetic patients].

PROactive is a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. Patients were assigned to oral pioglitazone titrated from 15 mg to 45 mg or matching placebo, to be taken in addition to their glucose-lowering drugs and other medications. After a mean follow up of 34.5 months, pioglitazone reduced the composite of all-cause mortality, non-fatal myocardial infarction, and stroke (intention to treat analysis: hazard ratio = 0.84; 95% CI: 0.72-0.98; p = 0.027). Various favourable metabolic effects could contribute to this cardiovascular protection, i.e. an absolute 0.5 % reduction in HbA1c, a 9% increase in HDL cholesterol, a 13% decline of triglycerides, and a 3 mm Hg reduction in systolic blood pressure in the pioglitazone group compared to placebo. The requirement of insulin was reduced by almost 50% in the pioglitazone group as compared to the placebo group. The incidence of cases of oedema and congestive heart failure was higher in the pioglitazone group. In conclusion, in patients with type 2 diabetes who are at high cardiovascular risk, pioglitazone improves cardiovascular outcome, and reduces the need to add insulin to glucose-lowering regimens compared to placebo.

Administration, Oral↗
PubMed2005

[Field, a randomized clinical trial of cardiovascular prevention with fenofibrate in type 2 diabetes].

FIELD ("Fenofibrate Intervention and Events Lowering in Diabetes") study compared the incidence of coronary and cardiovascular events in 4895 patients with type 2 diabetes treated with fenofibrate (micronized fomulation, 200 mg/day) and in 4900 patients treated with placebo. After a mean 5-year follow-up, the fenofibrate group did not have less coronary events (primary endpoint), neither present a significant reduction in cardiovascular or total mortality as compared to the placebo group. However, it had significantly less non-fatal myocardial infarctions and cardiovascular events in general as well as less coronary and total revascularization procedures (secondary endpoints). The higher rate of starting statin therapy in patients allocated placebo might have masked a larger treatment benefit of fenofibrate on macrovascular complications. The tolerance of fenofibrate was good, even in combination with statins. More surprisingly, fenofibrate exerted a favourable effect on microangiopathy complications, with less albuminuria progression and less retinopathy needing laser treatment (tertiary endpoints).

Aged↗
PubMed2004

Pathophysiology of insulin secretion.

Defects in pancreatic islet beta-cell function play a major role in the development of diabetes mellitus. Type 1 diabetes is caused by a more or less rapid destruction of pancreatic beta cells, and the autoimmune process begins years before the beta-cell destruction becomes complete, thereby providing a window of opportunity for intervention. During the preclinical period and early after diagnosis, much of the insulin deficiency may be the result of functional inhibition of insulin secretion that may be at least partially and transiently reversible. Type 2 diabetes is characterized by a progressive loss of beta-cell function throughout the course of the disease. The pattern of loss is an initial (probably of genetic origin) defect in acute or first-phase insulin secretion, followed by a decreasing maximal capacity of insulin secretion. Last, a defective steady-state and basal insulin secretion develops, leading to almost complete beta-cell failure requiring insulin treatment. Because of the reciprocal relation between insulin secretion and insulin sensitivity, valid representation of beta-cell function requires interpretation of insulin responses in the context of the prevailing degree of insulin sensitivity. This appropriate approach highlights defects in insulin secretion at the various stages of the natural history of type 2 diabetes and already present in individuals at risk to develop the disease. To date none of the available therapies can stop the progressive beta-cell defect and the progression of the metabolic disorder. The better understanding of the pathophysiology of the disease should lead to the development of new strategies to preserve beta-cell function in both type 1 and type 2 diabetes mellitus.

Animals↗
PubMed2004

Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials.

Most individuals with arterial hypertension or congestive heart failure are insulin-resistant and at a higher risk of developing type 2 diabetes (T2DM). The inhibition of the renin-angiotensin system (RAS), using an angiotensin converting enzyme inhibitor (ACEI) or a selective angiotensin receptor AT1 blocker (ARB), may exert favourable metabolic effects capable of preventing T2DM in high risk individuals. We performed a meta-analysis of randomised clinical trials (RCTs) assessing the effects of RAS inhibition on the incidence of new cases of T2DM in patients with arterial hypertension or congestive heart failure. Ten RCTs with cardiovascular prognosis as primary endpoints analysed the incidence of T2DM as secondary endpoints or as post-hoc analysis after a mean follow-up of 1 to 6 years: five with an ACEI and five with an ARB, compared with a placebo (n=4) or a reference drug (beta-blocker or diuretic: n=5; amlodipine: n=2). Eight RCTs concerned hypertensive patients: STOP Hypertension-2 (lisinopril or enalapril vs beta-blocker or diuretic), CAPPP (captopril vs thiazide or beta-blocker), HOPE (ramipril vs placebo), ALLHAT (lisinopril vs chlorthalidone and lisinopril vs amlodipine), LIFE (losartan vs atenolol), SCOPE (candesartan vs placebo), ALPINE (candesartan vs placebo) and VALUE (valsartan vs amlodipine). Two RCTs concerned patients with congestive heart failure: SOLVD (enalapril vs placebo) and CHARM-overall programme (candesartan vs placebo). Overall, 2 675 new cases of T2DM (7.40%) were observed in the group of 36 167 patients receiving a treatment with ACEI or ARA as compared with 3 842 events (9.63%) in the group of 39 902 control patients. A mean weighed relative risk reduction of new T2DM of 22% (95% CI: 18, 26; p<0.00001) was observed after RAS inhibition. The beneficial effect was similar with ACEIs and with ARBs as well as in patients with hypertension and in those with heart failure, and was also present whatever the comparator (placebo or beta-blockers/diuretics or amlodipine). The number needed-to-treat to avoid one new case of T2DM averaged 45 patients over 4-5 years. In conclusion, RAS inhibition consistently and significantly reduces the incidence of T2DM in individuals with arterial hypertension or with congestive heart failure. Considering the pandemic of T2DM, such pharmacological approach deserves further attention among the strategies aiming at preventing T2DM.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms.

The inhibition of the renin-angiotensin system (RAS) with either angiotensin converting enzyme inhibitors (ACEIs) or AT1 angiotensin receptor blockers (ARBs) consistently and significantly reduces the incidence of type 2 diabetes in patients with hypertension or congestive heart failure. The mechanisms underlying this protective effect appear to be complex and may involve an improvement of both insulin sensitivity and insulin secretion. These two effects may result, at least in part, from the well known effects of these pharmacological agents on the vascular system on the one hand, on the ionic balance on the other hand. Indeed, the vasodilation induced by ACEIs or ARBs could improve the blood circulation in skeletal muscles, thus favouring peripheral insulin action, but also in the pancreas, thus promoting insulin secretion. Preserving cellular potassium and magnesium pools by blocking the aldosterone effects could also improve both cellular insulin action and insulin secretion. However, besides these classical effects, new mechanisms have been recently suggested. A direct effect of the inhibition of angiotensin and/or of the enhancement of bradykinin on various steps of the insulin cascade signalling has been described as well an increase in GLUT4 glucose transporters after RAS inhibition. Furthermore, it has been demonstrated that angiotensin II inhibits adipogenic differentiation of human adipocytes via A1 receptors and, therefore, it has been hypothesised that RAS blockade may prevent diabetes by promoting the recruitment and differentiation of adipocytes. Finally, some lipophilic ARBs appear to induce PPAR-gamma activity in the adipose tissue. Hence, the protection against type 2 diabetes observed after RAS inhibition may be partially linked to a thiazolidinedione-like effect. In conclusion, numerous physiological and biochemical mechanisms could explain the protective effect of RAS inhibition against the development of type 2 diabetes in individuals with arterial hypertension or congestive heart failure. What might be the main mechanism in the overall protection effect of ACEIs or ARBs remains an open question.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Intact cross-talk between insulin secretion and insulin action after postgastroplasty recovery of ideal body weight in severely obese patients.

Most reports investigating the hormonal and metabolic effects of bariatric surgery studied obese subjects after partial weight loss only. Nevertheless, all studies showed significant improvements of insulin secretion, action, clearance and inhibition of its own secretion, although the parallel kinetics of all these changes remained questionable. Using the intravenous glucose tolerance test, we demonstrated a full normalization of insulin secretion, action on glucose metabolism and clearance in eight obese women who recovered and maintained ideal body weight following gastroplasty. Reciprocal changes were observed between postglucose acute insulin secretion and insulin-mediated glucose disposal so that the so-called disposition index (product of these two variables) remained unchanged after vs before gastroplasty in those individuals with normal glucose tolerance. These favourable results should encourage obtaining a drastic and sustained weight loss in patients with severe obesity at risk of developing type II diabetes.

Body Weight↗
PubMed2004

[Hematochromatosis and diabetes].

Nowadays, haemochromatosis is often diagnosed when the patient is monosymptomatic. Diabetes is frequently the first expression of the disease. So, it is important to know the clinical and biologic characteristics to evoke diagnosis as early as possible. Uncommon presentations request systematic screening.

Asthenia↗
PubMed2004

[Drug of the month. Rosuvastatin (Crestor)].

Rosuvastatin (Crestor) has been recently launched in Belgium by AstraZeneca. This new statin is indicated for the treatment of primary hypercholesterolaemia or combined dyslipidaemia, when changes in dietary habits are insufficient. Direct comparative randomised clinical trials with other statins demonstrated that rosuvastatin exerts a more favourable impact on lipid profile. When compared on a mg basis to other statins, rosuvastatin is associated with a greater reduction in total and LDL cholesterol levels and a greater increase of HDL cholesterol concentration, with a similar decrease in triglyceride levels. At the usual dosage of 10 mg, rosuvastatin allowed to reduce LDL cholesterol below recommended target levels for at risk patients among almost 80% of treated individuals in phase III clinical trials. If necessary, the daily dosage may be increased to 20 mg, or up to 40 mg (maximal dose), mostly in case of severe familial hypercholesterolaemia. Safety profile is good and similar to that of other commercialised statins. Rosuvastatin is currently evaluated in an extensive programme of randomised clinical trials (Galaxy programme) in order to demonstrate its efficacy in both prevention of atherosclerosis and reduction of cardiovascular morbidity and mortality.

Anticholesteremic Agents↗
PubMed2004

[Medication of the month. Insulin glargine (Lantus)].

Insulin glargine (Lantus) is a human insulin analogue produced by recombinant DNA technology and recently launched by Aventis. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue (pH > 7,4) from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant over 24 hours as compared to conventional human insulins, especially NPH. This allows once-daily injection as basal insulin therapy, at any moment of the clock time (but if possible at the same time from day to day). Reproducibility of plasma insulin levels is also improved with insulin glargine as compared to human NPH insulin. Insulin glargine administration should be combined to rapid insulin injections, before each meal in order to control postprandial hyperglycaemia, or with oral antidiabetic agents in type 2 diabetes. The pharmacokinetic properties of insulin glargine allow an easier titration of basal insulin dose, which should facilitate adequate blood glucose control while decreasing the risk of hypoglycaemia, especially during night time. Insulin glargine use is safe with no increased antigenicity, immunogenicity or mitogenicity reactions as compared to human insulin. Optimal use of this new insulin analogue should be integrated in a global management of the diabetic patient as well as in a new culture of insulin therapy.

Diabetes Mellitus↗