Publications of Bernard JANDRAIN
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See detailA Randomized Study to Compare a Monthly to a Daily Administration of Vitamin D(3) Supplementation.
De Niet, Sophie; Coffiner, Monte; Da Silva, Stephanie et al

in Nutrients (2018), 10(6),

We aimed to determine whether a cumulative dose of vitamin D(3) produces the same effects on the serum concentration of 25(OH)D(3) if it is given daily or monthly. This is a monocentric, two-armed ... [more ▼]

We aimed to determine whether a cumulative dose of vitamin D(3) produces the same effects on the serum concentration of 25(OH)D(3) if it is given daily or monthly. This is a monocentric, two-armed, randomized, interventional, open, and parallel study conducted from November 2016 to March 2017 in Belgium. We randomized 60 subjects with vitamin D deficiency to receive 2000 IU vitamin D(3) daily or 50,000 IU monthly. The same cumulative dose of vitamin D(3) was given to each treatment group (150,000 IU). The 25(OH)D(3) serum concentrations from baseline to day 75 were 14.3 +/- 3.7 to 27.8 +/- 3.9 ng/mL in the monthly group and 14.1 +/- 3.4 to 28.8 +/- 5.4 ng/mL in the daily group. The mean change versus the baseline level was significantly different between the groups at day 2, 4, 7, and 14 and no longer different from day 25. One day after the intake of vitamin D(3), as expected, serum 25(OH)D(3) and 1,25(OH)(2)D(3) increased significantly in the monthly group, whereas they did not change significantly in the daily group. The median time to reach the 20 ng/mL target concentration was significantly different in the two groups, in favor of the monthly regimen (1 day versus 14 days; p = 0.02). In conclusion, a monthly administration of 50,000 IU vitamin D(3) provides an effective tool for a rapid normalization of 25(OH)D(3) in deficient subjects. A daily administration of the same cumulative dose is similarly effective but takes two weeks longer to reach the desirable level of 20 ng/mL. [less ▲]

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See detailA randomized study to compare a monthly to a daily administration of vitamin D3 supplementation
De Niet, Sophie; Coffiner, Monte; Da Silva, Stéphanie et al

in Nutrients (2018), 10(6),

We aimed to determine whether a cumulative dose of vitamin D3 produces the same effects on the serum concentration of 25(OH)D3 if it is given daily or monthly. This is a monocentric, two-armed, randomized ... [more ▼]

We aimed to determine whether a cumulative dose of vitamin D3 produces the same effects on the serum concentration of 25(OH)D3 if it is given daily or monthly. This is a monocentric, two-armed, randomized, interventional, open, and parallel study conducted from November 2016 to March 2017 in Belgium. We randomized 60 subjects with vitamin D deficiency to receive 2000 IU vitamin D3 daily or 50,000 IU monthly. The same cumulative dose of vitamin D3 was given to each treatment group (150,000 IU). The 25(OH)D3 serum concentrations from baseline to day 75 were 14.3 ± 3.7 to 27.8 ± 3.9 ng/mL in the monthly group and 14.1 ± 3.4 to 28.8 ± 5.4 ng/mL in the daily group. The mean change versus the baseline level was significantly different between the groups at day 2, 4, 7, and 14 and no longer different from day 25. One day after the intake of vitamin D3, as expected, serum 25(OH)D3 and 1,25(OH)2 D3 increased significantly in the monthly group, whereas they did not change significantly in the daily group. The median time to reach the 20 ng/mL target concentration was significantly different in the two groups, in favor of the monthly regimen (1 day versus 14 days; p = 0.02). In conclusion, a monthly administration of 50,000 IU vitamin D3 provides an effective tool for a rapid normalization of 25(OH)D3 in deficient subjects. A daily administration of the same cumulative dose is similarly effective but takes two weeks longer to reach the desirable level of 20 ng/mL. © 2018 by the authors. Licensee MDPI, Basel, Switzerland. [less ▲]

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See detailLa complémentarité entre essais cliniques contrôlés et registres observationnels : L'exemple des études de prévention cardiovasculaire avec les inhibiteurs des SGLT2
Scheen, André ULiege; ERNEST, Philippe ULiege; JANDRAIN, Bernard ULiege

in Revue Médicale de Liège (2017), 72(12), 563-568

Evidence-based medicine (EBM) is mainly supported by the results of randomised controlled trials (RCTs). If the latter offer guarantees of reliability, especially by minimizing the influence of ... [more ▼]

Evidence-based medicine (EBM) is mainly supported by the results of randomised controlled trials (RCTs). If the latter offer guarantees of reliability, especially by minimizing the influence of confounding factors and potential biases, they also have limitations. Observational databases resulting from real life registries, if possible build in a prospective manner, may offer some solutions, but are also exposed to limitations. This article compares the advantages and disadvantages of the two sources of information, which ideally should be complementary. For the purpose of illustration, we shall compare the recent results of RCTs and of observational databases from multinational registries that investigated the effects of sodium-glucose cotransporter type 2 inhibitors (gliflozins) on cardiovascular outcomes in patients with type 2 diabetes. [less ▲]

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See detailProtection cardio-renale par les inhibiteurs des SGLT2 (gliflozines) : d'EMPA-REG OUTCOME a CANVAS.
Scheen, André ULiege; Ernest, Philippe ULiege; Jandrain, Bernard ULiege

in Revue Médicale Suisse (2017), 13(571), 1421-1426

The cardiovascular (CV) and renal protection reported with empagliflozin in EMPA-REG OUTCOME is now confirmed with canagliflozin in CANVAS in patients with type 2 diabetes and high cardiovascular risk ... [more ▼]

The cardiovascular (CV) and renal protection reported with empagliflozin in EMPA-REG OUTCOME is now confirmed with canagliflozin in CANVAS in patients with type 2 diabetes and high cardiovascular risk: similar and significant reductions in major CV events (-14 vs. -14%), in hospitalisations for heart failure (-35 vs. -33%) and in renal events (-39 vs. -40%). The greater reduction in CV mortality (-38 vs. - 13%) and all-cause mortality (-32 vs. -13%) in EMPA-REG OUTCOME than in CANVAS may be explained by the greater proportion of patients with CV disease (secondary prevention : 99 vs. 65%). In contrast to EMPA-REG OUTCOME, CANVAS did not show an increase in stroke (-10%, NS), but reported a higher rate of fractures and amputations with canagliflozin. Overall, these results support a class effect for the cardiorenal protection by inhibitors of sodium-glucose type 2 (SGLT2) cotransporters. [less ▲]

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See detailProtection cardiovasculaire du patient diabetique de type 2 : d'EMPA-REG OUTCOME a LEADER.
Scheen, André ULiege; WALLEMACQ, Caroline ULiege; Jandrain, Bernard ULiege et al

in Revue Médicale Suisse (2016), 12(527), 1370-1375

Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type ... [more ▼]

Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME, and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER, showed a significant reduction in major cardiovascular events (- 14 and - 13 %, respectively), cardiovascular mortality (- 38 and - 22 %, respectively) and all-cause mortality (- 32 and - 15 %, respectively). A lower progression of kidney disease and less renal events were also reported. The underlying protective mechanisms remain controverted as the discussion whether the benefits are specific to each medication or could be extended to other molecules of these two pharmacological classes. [less ▲]

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See detailForces et faiblesse des essais cliniques . Evolution en fonction de l'essor de la medecine personnalisee.
Ernest, Philippe ULiege; Jandrain, Bernard ULiege; Scheen, Andre ULiege

in Revue Médicale de Liège (2015), 70(5-6), 232-6

Randomised Controlled Trials (RCTs) represent the cornerstone of Evidence-Based Medicine (EBM). Based upon the rules of Good Clinical Practice (GCP), they offer many strengths but also present some ... [more ▼]

Randomised Controlled Trials (RCTs) represent the cornerstone of Evidence-Based Medicine (EBM). Based upon the rules of Good Clinical Practice (GCP), they offer many strengths but also present some weaknesses. The rigorous methodology used allows avoid bias related to confounding factors (through a control group), selection bias (through randomisation) and interpretation bias (through double blinding). However, patients recruited in clinical trials and study experimental conditions markedly differ from the situation in real life. Furthermore, clinical trials recruit a mix of good and poor responders, so that the average therapeutic response is most often mitigated. Clinical trials must evolve according to the new concepts of personalized medicine to become even more performing. In a near future, they must progress from a statistical analysis on large cohorts of patients to a more individualized analysis guided by patient phenotype and genotype characteristics. [less ▲]

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See detailComment j’explore …Une différence de risque de survenue d’un événement dans les études cliniques
SCHEEN, André ULiege; ERNEST, Philippe ULiege; JANDRAIN, Bernard ULiege

in Revue Médicale de Liège (2012), 67(11), 597-602

Evidence-based medicine often requires the comparison of two therapeutic interventions in controlled clinical trials with the demonstration of a superiority (versus a placebo or an active comparator) or ... [more ▼]

Evidence-based medicine often requires the comparison of two therapeutic interventions in controlled clinical trials with the demonstration of a superiority (versus a placebo or an active comparator) or at least a non-inferiority (versus an active reference) concerning a primary endpoint that has been defined a priori (occurrence of a major clinical event, for instance). The difference in the occurrence of such an event between two treatments may be statistically analyzed by absolute risk reduction, relative risk reduction, hazard ratio or odds ratio. The present article discusses the nuances, sometimes of importance, concerning the significance of these various indices and analyses the cautions to be taken and the pitfalls to be avoided in their interpretation and use in practice. The clinician is, indeed, increasingly confronted to results of clinical trials, but is generally poorly informed regarding the nuances of these various statistical analyses. [less ▲]

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See detailInhibiteurs du cotransporteur du glucose SGLT rénal pour traiter le diabète de type 2
SCHEEN, André ULiege; RADERMECKER, Régis ULiege; ERNEST, Philippe ULiege et al

in Revue Médicale Suisse (2011), 7(306), 1621-1629

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See detailInhibiteurs du cotransporteur du glucose SGLT2 renal pour traiter le diabete de type 2.
SCHEEN, André ULiege; Radermecker, Régis ULiege; Ernest, Philippe ULiege et al

in Revue Médicale Suisse (2011), 7(306), 1621-41626-9

Kidney plays a role in glucose homeostasis, not only by its capacity to produce glucose through local gluconeogenesis, but also, and even more important in presence of diabetes, by its capacity to excrete ... [more ▼]

Kidney plays a role in glucose homeostasis, not only by its capacity to produce glucose through local gluconeogenesis, but also, and even more important in presence of diabetes, by its capacity to excrete glucose in urine when hyperglycaemia exceeds tubular reabsorption threshold. Such reabsorption depends on sodium-glucose cotransporters-2 (SGLT2), which can be blocked by selective inhibitors. These pharmacological agents augment glucosuria and reduce hyperglycaemia independently of insulin. Some have already proven their efficacy to improve glucose control, in monotherapy or in combination, while promoting weight loss and without inducing hypoglycaemia. Dapagliflozin should be the first medication of this new pharmacological class to be commercialized for the management of type 2 diabetes. [less ▲]

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See detailStrategies pour eviter l'inertie et la non-observance dans les essais cliniques.
Jandrain, Bernard ULiege; Ernest, Philippe ULiege; Radermecker, Régis ULiege et al

in Revue Médicale de Liège (2010), 65(5-6), 246-9

Randomised controlled trials play a key role in evidence-based medicine as far as the assessment of both efficacy and safety of drugs is concerned. Various strategies are used to avoid physician's inertia ... [more ▼]

Randomised controlled trials play a key role in evidence-based medicine as far as the assessment of both efficacy and safety of drugs is concerned. Various strategies are used to avoid physician's inertia and to combat patient's non compliance, two pitfalls that may hinder the demonstration of the therapeutic efficacy of the drug. Clinical inertia may be limited by titration, forced or optional, driven by therapeutic targets, or by the use, if necessary, of rescue medications. Compliance may be verified by "pill count". This simple technique allows to exclude non compliant patients when they are detected during the placebo run-in period before randomisation or not to take into account patients with poor compliance in the final evaluation by using a statistical analysis restricted to individuals who have strictly adhered to the study protocol ("per protocol analysis"). Self-monitoring and patient's empowerment in the treatment also contribute to improve drug compliance. Clinicians may take advantage of these approaches derived from clinical trials to improve their daily practice. [less ▲]

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See detailOptimisation du traitement pharmacologique chez un patient avec un diabete de type 2 nouvellement diagnostique.
De Flines, Jenny ULiege; Radermecker, Régis ULiege; Jandrain, Bernard ULiege et al

in Revue Médicale de Liège (2009), 64(2), 109-14

The diabetic patient, when type 2 diabetes is newly diagnosed, raises a therapeutic problem commonly observed in clinical practice, which is more complex than expected at first glance. The physician has ... [more ▼]

The diabetic patient, when type 2 diabetes is newly diagnosed, raises a therapeutic problem commonly observed in clinical practice, which is more complex than expected at first glance. The physician has to select the most appropriate antidiabetic oral agent as first choice, to consider the potential of using combined glucose-lowering therapies, to fix glycaemic target taking into account the individual benefit/risk ratio, and to offer the best protection against cardiovascular complications. The present clinical case illustrates such therapeutic problem describing a patient with a high cardiovascular risk profile who experienced a hypoglycaemic episode after the prescription of glibenclamide following the discovery of a moderate hyperglycaemia. [less ▲]

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See detailL'etude clinique du mois. Controle glycemique et morbimortalite cardio-vasculaire chez le patient diabetique de type 2. Resultats des etudes ACCORD, ADVANCE et VA-Diabetes.
Radermecker, Régis ULiege; Philips, Jean-Christophe ULiege; Jandrain, Bernard ULiege et al

in Revue Médicale de Liège (2008), 63(7-8), 511-8

Type 2 diabetes is associated with a high risk of complications, essentially macrovascular events. Surprisingly, the effect of improved glucose control on coronary and cerebrovascular complications in ... [more ▼]

Type 2 diabetes is associated with a high risk of complications, essentially macrovascular events. Surprisingly, the effect of improved glucose control on coronary and cerebrovascular complications in this population remains questionable. Furthermore, the target level of glycated haemoglobin (HbA1c) to minimise the risk of diabetic complications is controversial. We report the results of three recent randomised control trials (ACCORD, ADVANCE, Veterans Affairs Diabetes), which assessed the impact on cardiovascular events of intensive glucose-lowering therapy. None of these studies was able to demonstrate a significant reduction of cardiovascular events in the intensive group as compared to the standard group. On the contrary, in ACCORD, the study with the most ambitious goal (HbA1c < 6%), the overall and cardiovascular mortality was greater in the intensive group. In contrast, in the ADVANCE trial, the mortality and the incidence of cardiovascular events were not statistically different between the two treatment groups, whereas the risk of microangiopathic complications, especially nephropathy, was significantly decreased in the intensive group (HbA1c < or = 6.5%, with modified release gliclazide as main treatment). Finally, VA-Diabetes showed that the effect of better glucose control on cardiovascular complications disappeared with duration of the disease and that the risk of cardiovascular events increased in patients with severe hypoglycaemic episodes. In the three studies, the hypoglycaemic risk was indeed increased in the intensive group, which may contribute to reduce the positive impact of better glucose control on cardiovascular complications. The best way to protect type 2 diabetic patients against coronary and cerebrovascular disease is to target all cardiovascular risk factors. [less ▲]

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See detailLe cerveau, un organe gluco-dependant. Effets deleteres de l'hypoglycemie et de l'hyperglycemie.
Radermecker, Régis ULiege; Philips, Jean-Christophe ULiege; Jandrain, Bernard ULiege et al

in Revue Médicale de Liège (2008), 63(5-6), 280-6

Glucose is almost the only energy substrate for the brain. Such glucose dependence explains why any large variation of plasma glucose levels could lead to cerebral dysfunction, which may be severe and ... [more ▼]

Glucose is almost the only energy substrate for the brain. Such glucose dependence explains why any large variation of plasma glucose levels could lead to cerebral dysfunction, which may be severe and progress to a coma. Hypoglycaemic coma, the most common one, has a pure metabolic origin (neuroglucopenia) whereas hyperglycaemic coma is more complex and mainly due to osmotic disturbances. Besides acute changes of plasma glucose concentrations, it is generally recognized that more subtle chronic or recurrent glucose abnormalities could also result in brain dysfunction. However, such clinical consequences are more difficult to assess in clinical practice. Nevertheless, learning perturbations in young patients with type 1 diabetes and memory losses, sometimes severe and subject to progress to dementia ("diabetic encephalopathy") in older type 1 or type 2 diabetic patients, have been reported, although with some controversy. The present paper summarizes the current knowledge of both acute and chronic cerebral dysfunctions following perturbations of blood glucose levels in diabetic patients. [less ▲]

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See detailAlcool, sensibilite a l'insuline et diabete sucre.
Magis, Delphine ULiege; Jandrain, Bernard ULiege; Scheen, André ULiege

in Revue Médicale de Liège (2003), 58(7-8), 501-7

The relationship between alcohol consumption and insulin resistance shows a U-shaped curve: insulin resistance is minimal in individuals with regular mild to moderate alcohol consumption and increases in ... [more ▼]

The relationship between alcohol consumption and insulin resistance shows a U-shaped curve: insulin resistance is minimal in individuals with regular mild to moderate alcohol consumption and increases in both heavy drinkers and subjects without any alcohol consumption. These favourable metabolic effects on insulin sensitivity of moderate alcohol consumption may explain the significant reduction in the development of type 2 diabetes and the risk of cardiovascular complications reported in numerous epidemiological studies. This latter effect has also reported in patients with diabetes mellitus, although this observation remains controversial. However, alcohol consumption could increase the global risk of hypoglycaemia, both in the fasting state and after a meal (reactive hypoglycaemia) in both diabetic and nondiabetic subjects. These latter effects may result from a direct inhibition of gluconeogenesis, from a reduced secretion of counterregulatory hormones and/or from an alcohol-induced inappropriate behaviour. [less ▲]

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See detailPrevention des hypoglycemies chez le patient diabetique de type 1.
Radermecker, Régis ULiege; Jandrain, Bernard ULiege; Paquot, Nicolas ULiege et al

in Revue Médicale de Liège (2003), 58(6), 361-8

Hypoglycaemia is the most common metabolic disorder in type 1 diabetic patients. It is rarely dangerous, but significantly alters the quality of life and hinders the achievement of "normoglycaemia". Even ... [more ▼]

Hypoglycaemia is the most common metabolic disorder in type 1 diabetic patients. It is rarely dangerous, but significantly alters the quality of life and hinders the achievement of "normoglycaemia". Even if hypoglycaemia is impossible to be avoided, both its frequency and severity may be reduced if patients follow several practical recommendations. After having defined hypoglycaemia, we shall briefly describe its pathophysiology and its main causes in type 1 diabetic patients. Afterwards, the different approaches of prevention of hypoglycaemia will be discussed. We will particularly stress the need to revise the glycaemic target in high-risk patients, the role of optimising insulin therapy, the valuable help of blood glucose monitoring, the critical support of diet adjustments, and the appropriate management in case of physical activity. There is no doubt that patient's education plays a crucial role in such a strategy that aims at preventing severe hypoglycaemia in type 1 diabetic individuals. [less ▲]

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See detailL'hyperglycemie post-prandiale. I. Physiopathologie, consequences cliniques et approaches dietetiques.
Scheen, André ULiege; Paquot, Nicolas ULiege; Jandrain, Bernard ULiege et al

in Revue Médicale de Liège (2002), 57(3), 138-41

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 ... [more ▼]

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. [less ▲]

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See detailComment j'explore ... Le risque d'un patient d'evoluer vers un diabete de type 2.
Scheen, André ULiege; Paquot, Nicolas ULiege; Jandrain, Bernard ULiege

in Revue Médicale de Liège (2002), 57(2), 113-5

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 ... [more ▼]

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. [less ▲]

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See detailApproches pharmacologiques de prévention du diabète de type 2.
SCHEEN, André ULiege; PAQUOT, Nicolas ULiege; LETIEXHE, Michel ULiege et al

in Médecine et Hygiène (2002), 60

L’augmentation rapide de la prévalence du diabète de type 2 impose la mise en place de stratégies de prévention. Outre les mesures hygiéno-diététiques, essentielles, diverses approches pharmacologiques ... [more ▼]

L’augmentation rapide de la prévalence du diabète de type 2 impose la mise en place de stratégies de prévention. Outre les mesures hygiéno-diététiques, essentielles, diverses approches pharmacologiques ont apporté récemment la preuve d’une certaine efficacité chez les sujets à risque de par la présence d’un excès pondéral et/ou d’une diminution de la tolérance au glucose. C’est le cas de plusieurs antidiabétiques oraux comme la metformine, l’acarbose ou encore la troglitazone. C’est également le cas de médicaments anti-obésité comme l’orlistat et, peut-être aussi, la sibutramine. L’inhibition du système rénine-angiotensine par un inhibiteur de l’enzyme de conversion ou par un antagoniste sélectif des récepteurs AT1 peut aussi, outre protéger contre les complications cardiovasculaires, prévenir l’apparition d’un diabète de type 2. Enfin, le rôle des médicaments hypolipidémiants reste controversé. De nouvelles études prospectives sont en cours pour confirmer ces résultats. [less ▲]

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See detailL'hyperglycemie post-prandiale. II. Approches therapeutiques medicamenteuses.
Scheen, André ULiege; Letiexhe, Michel ULiege; Geronooz, I. et al

in Revue Médicale de Liège (2002), 57(4), 196-201

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 ... [more ▼]

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. [less ▲]

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