Estimation de la sensibilité à l'insuline par le "minimal model" : comparaison de différents protocoles d'hyperglycémie provoquée intraveineuse.
SCHEEN, André ; LETIEXHE, Michel ; DUYSINX, Bernard et al
in Diabète & Métabolisme (1994), 20(suppl),Detailed reference viewed: 6 (0 ULg)
Pharmacological treatment of the obese diabetic patient.
Scheen, André ; Lefebvre, Pierre
in Diabète & Métabolisme (1993), 19(6), 547-59
Obesity is a well-known risk factor for non-insulin-dependent (or Type 2) diabetes mellitus. Consequently, reduction of weight excess comes to the front line in the prevention and management of NIDDM. It ... [more ▼]
Obesity is a well-known risk factor for non-insulin-dependent (or Type 2) diabetes mellitus. Consequently, reduction of weight excess comes to the front line in the prevention and management of NIDDM. It is only when diet and physical exercise fail that drug treatment should be considered. Pharmacological treatment of obesity should favour drugs which not only promote weight loss, by reducing caloric intake and/or increasing thermogenesis and energy expenditure, but also, and especially, improve insulin sensitivity. Serotoninergic anorectic compounds (dexfenfluramine, fluoxetine) appear to possess, to some extent, all these properties. Metformin significantly reduces insulin resistance and improves glycaemic control without inducing weight gain, and even favouring some weight loss. This biguanide is now considered as the first line drug for the obese diabetic patient. Alpha-glucosidase inhibitors may help to reduce post-prandial glucose excursions but do not promote weight loss per se. Sulfonylureas can be prescribed to an obese patient when hyperglycaemia persists despite diet and the above-mentioned oral agents, but their use should be associated with reinforcement of dietary advices in order to prevent further weight increase; it is also the case for insulin therapy. Finally, drugs specifically stimulating thermogenesis and energy expenditure, new agents sensitizing tissues to the action of insulin and various compounds interfering with lipid metabolism are currently under extensive investigation with promising preliminary results in the obese diabetic patient. In conclusion, obesity remains a major problem in the management of Type 2 diabetes mellitus and this justifies the search for new, safe and effective, pharmacological approaches. [less ▲]Detailed reference viewed: 13 (0 ULg)
Effets de l'amaigrissement sur la sensibilité à l'insuline chez le sujet obèse non diabétique: étude par le "Minimal Model" lors d'une hyperglycémie provoquée par voie intraveineuse.
LETIEXHE, Michel ; SCHEEN, André ; PAQUOT, Nicolas et al
in Diabète & Métabolisme (1993), 19(suppl),Detailed reference viewed: 14 (0 ULg)
Mesure de la sensibilité à l'insuline par le "minimal model" de Bergman au cours d'une hyperglycémie provoquée par voie intraveineuse: validation de la possibilité de réduire le nombre de prélèvements sanguins
DUYSINX, Bernard ; SCHEEN, André ; et al
in Diabète & Métabolisme (1993), 19(suppl),Detailed reference viewed: 9 (1 ULg)
Impaired immune responses in diabetes mellitus: analysis of the factors and mechanisms involved. Relevance to the increased susceptibility of diabetic patients to specific infections.
Moutschen, Michel ; Scheen, André ; Lefebvre, Pierre
in Diabète & Métabolisme (1992), 18(3), 187-201
The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear. The virtual absence of epidemiological studies of the independent risk ... [more ▼]
The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear. The virtual absence of epidemiological studies of the independent risk factors involved contrasts with the multitude of in vitro models focused on the metabolism and function of immune cells from diabetic patients. This review analyzes some of these models and their clinical relevance. The different levels of diabetes pathogenesis: genetic (Type 1), autoimmune (Type 1) and metabolic (Type 1 and Type 2) are responsible for immune abnormalities demonstrated in in vitro models. The participation of genetic and autoimmune factors has been mainly characterized on T lymphocyte function. The B8 DR3 haplotype is associated with several minor immunologic abnormalities in vitro. However, the high frequency of this haplotype in healthy individuals argues against its involvement in significant defects of antimicrobial immunity. Genetic deficiency of C4, present in 25% of Type 1 diabetic patients could, on the other hand, be responsible for opsonization defects against encapsulated pathogens. Several immunological abnormalities related to the autoimmune process preceding the onset of Type 1 diabetes mellitus, such as the depletion of memory CD4+ cells and the defective natural killer activity could transiently impair host defences against viral diseases. Several in vitro functional defects of the immune system have been correlated with the metabolic control of diabetic patients. This suggests the involvement of insulinopenia in some of the abnormalities observed. Insulinopenia-induced enzymatic defects have often been proposed to inhibit energy-requiring functions of phagocytes and lymphocytes. However, the relevance of this mechanism could be confined to patients with extremely severe metabolic abnormalities. The importance of systemic consequences of insulinopenia such as hyperglycaemia and ketosis has also been addressed. Usually, the defects induced in vitro by these factors are slight and require supraphysiologic concentrations of glucose or ketone bodies. Recent studies have shown abnormalities of signal transduction mechanisms in which insulinopenia itself and other factors such as circulating immune complexes could be involved. Despite numerous controversies, many in vitro studies of the immune cells of diabetic patients have demonstrated significant defects which bear quantitative similarities with abnormalities described in other immunodeficiency syndromes. Furthermore, several mechanisms have been proposed to link the different defects observed with the specific infections encountered in diabetic patients. [less ▲]Detailed reference viewed: 48 (3 ULg)
Absence de benefice de l'administration intermittente de l'insuline lors d'un traitement par pompe a perfusion sous-cutanee chez le diabetique de type-1.
Lilet, Henri ; ; Bodson, Arthur et al
in Diabète & Métabolisme (1991), 17(3), 363-72
Our study is based on two constatations: 1) Hyperinsulinaemia, a possible atherogenic factor, is frequent under continuous subcutaneous insulin infusion. 2) Pulsatile intravenous insulin delivery improve ... [more ▼]
Our study is based on two constatations: 1) Hyperinsulinaemia, a possible atherogenic factor, is frequent under continuous subcutaneous insulin infusion. 2) Pulsatile intravenous insulin delivery improve the insulin's hypoglycaemic activity. To test if equivalent metabolic control can be obtained with a reduced intermittent subcutaneous infused insulin dose, we compared nocturnal metabolic control of 8 c-peptide negative type 1 diabetic patients under three experimental conditions: Continuous usual dose test (1.0 +/- 0.1 u/h); Intermittent half dose test (1.0 +/- 0.1 u/h, 30 min/h); Continuous half dose test (0.5 +/- 0.05 u/h) Five parameters were monitored: blood glucose, plasma free insulin and beta-hydroxy-butyrate, free fatty acid and glycerol plasma level. No significant differences were found between intermittent and continuous half-dose tests. We conclude that, in our experimental conditions, intermittent subcutaneous insulin infusion does not reduce the metabolic degradation induced by insulin dose reduction. [less ▲]Detailed reference viewed: 27 (1 ULg)
Pharmacocinetique de l'insuline administree par voie sous-cutanee. Application au traitement par pompe portable (1).
in Diabète & Métabolisme (1989), 15(3), 128-38
Continuous subcutaneous insulin infusion is characterized by a basal insulin delivery rate to which insulin boluses are added. The basal delivery rate maintains a small insulin reserve in the local ... [more ▼]
Continuous subcutaneous insulin infusion is characterized by a basal insulin delivery rate to which insulin boluses are added. The basal delivery rate maintains a small insulin reserve in the local subcutaneous depot. This reserve averages 2 to 5 times the hourly basal rate at the steady-state which is reached after about 7 hours but depends on numerous factors: subcutaneous blood flow, skinfold thickness, insulin concentration, etc. It explains the pharmacokinetics time-lag of the system, more particularly the similar effects of a basal rate delivered in either a pulsatile/intermittent or a continuous manner, the lack of deleterious effect of a 1-h pump arrest, the 2-h delay before significant metabolic deterioration during a more prolonged interruption of the infusion, the delayed plasma insulin changes when the basal insulin delivery rate is doubled or reduced by half, etc. Insulin boluses pharmacokinetics is not fundamentally different from that of soluble insulin injection in conventional therapy. As an example, insulin boluses should ideally be given 30 min before the meals in order to better prevent post-prandial hyperglycaemia. However, the absence of intermediate zinc-insulin in the system may result in an earlier increase of plasma free insulin levels, which for instance allows a rapid correction of the metabolic alterations induced by a prolonged interruption of the basal infusion rate. This kinetics does not seem to be significantly altered by insulin concentration nor by the profile of the bolus but is affected by the insulin content of the subcutaneous depot at the time the bolus is delivered.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]Detailed reference viewed: 68 (0 ULg)
Prostaglandines, secretion d'insuline et diabete sucre.
; ; Scheen, André et al
in Diabète & Métabolisme (1988), 14(6), 721-7
The islets of Langerhans have the enzymatic equipment permitting the synthesis of the metabolites of arachidonic acid: cyclo-oxygenase and lipo-oxygenase. Numerous studies have shown that cyclo-oxygenase ... [more ▼]
The islets of Langerhans have the enzymatic equipment permitting the synthesis of the metabolites of arachidonic acid: cyclo-oxygenase and lipo-oxygenase. Numerous studies have shown that cyclo-oxygenase derivatives, mainly PGE2, reduce the insulin response to glucose whereas lipo-oxygenase derivatives, mainly 15-HPETE, stimulate insulin secretion. So, for instance, drugs that increase prostaglandins synthesis as colchicine or furosemide inhibit insulin secretion while non steroid anti-inflammator drugs, mainly salicylates, which inhibit cyclo-oxygenase, enhance the insulin response to various stimuli. In type-2 (non insulin-dependent) diabetes, an increased sensitivity to endogenous prostaglandins has been proposed as a possible cause for the insulin secretion defect which characterizes this disease. Play in favor of this hypothesis the fact that the administration of PGE inhibits the insulin response to arginine in type-2 diabetics but not in normal subject and the fact that the administration of salicylates could improve the insulin response to glucose in some of these patients. [less ▲]Detailed reference viewed: 45 (0 ULg)
Adaptations au sport du diabetique traite par insuline.
Jandrain, Bernard ; Pirnay, Freddy ; Scheen, André et al
in Diabète & Métabolisme (1988), 14(2), 127-35
Performing muscular exercise regularly is generally recommended to diabetics; indeed, exercise increases muscle insulin sensitivity, helps fighting overweight and, at least partly, tends to correct plasma ... [more ▼]
Performing muscular exercise regularly is generally recommended to diabetics; indeed, exercise increases muscle insulin sensitivity, helps fighting overweight and, at least partly, tends to correct plasma lipids abnormalities, thus contributing to limit the development of atherosclerosis. Moreover, the practice of sport is beneficial from a psychological point of view, because, thanks to it, diabetic patients can match, even surpass, "the others" and overcome what they often consider as a disability. However, diabetes--especially type 1, insulin dependent, diabetes--deeply modifies the metabolic adaptations to muscular exercise; consequently, exercise must be performed only in good metabolic control conditions, for avoiding a worsening of ketonaemia. In adequately controlled diabetics, muscular exercise can be beneficial by reducing blood glucose levels; it can also lead to hypoglycaemia occurring during or after the exercise bout. In order to reduce the risk of exercise-induced hypoglycaemia, diabetics have to know how to modify three essential parameters of their treatment: (1) increase carbohydrate intake before, during or after exercise; (2) reduce the dose of the insulin acting during exercise, and this in relation to the usual doses and to exercise intensity; (3) under some circumstances, modify the site of insulin injection according to the type of exercise performed. Taking into account these parameters, some general rules can be assessed, which are to be adapted to every particular situation; the use of home blood glucose monitoring before and after exercise is not only useful but sometimes mandatory.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]Detailed reference viewed: 117 (8 ULg)
Renal function and albumin excretion rate in acromegaly : evidence for glomerular hyperfiltration
; Beckers, Albert ; Stevenaert, Achille et al
in Diabète & Métabolisme (1988), 14Detailed reference viewed: 7 (0 ULg)
The intra-nasal administration of insulin induces significant hypoglycaemia and classical counterregulatory hormonal responses in normal man.
Paquot, Nicolas ; Scheen, André ; et al
in Diabète & Métabolisme (1988), 14(1), 31-6
The present study aimed at investigating the metabolic and hormonal consequences of intra-nasal administration of insulin in normal man. Lyophylisated regular porcine insulin (Insuline Ordinaire Organon ... [more ▼]
The present study aimed at investigating the metabolic and hormonal consequences of intra-nasal administration of insulin in normal man. Lyophylisated regular porcine insulin (Insuline Ordinaire Organon) diluted with a non ionic detergent (Laureth-9 0,25%) was administered intra-nasally in 8 overnight fasted healthy volunteers using a calibrated aerosol delivery device (90 microliters = 9 U of insulin/spray) up to a total insulin dose close to 1 U/kg body weight. After intra-nasal insulin administration, plasma insulin levels rose from 5 +/- 1 to 38 +/- 10 mU/l (2p less than 0.01) at min 15, blood glucose concentrations decreased from 4.4 +/- 0.2 to 3.2 +/- 0.3 mmol/l (2p less than 0.01) at min 45, plasma C-peptide levels diminished from 327 +/- 31 to 174 +/- 28 mumol/l (2p less than 0.01) at min 60 and plasma free fatty acids concentrations fell from 336 +/- 109 to 130 +/- 31 mumol/l (2p less than 0.05) at min 30. The fall in blood glucose resulted in a prompt increase in plasma glucagon levels (from 78 +/- 28 to 150 +/- 24 ng/l at min 45; 2p less than 0.05) and in later rises in plasma growth hormone and cortisol concentrations. There was a close relationship between the individual maximal decreases in blood glucose levels and the individual maximal increases in plasma insulin (r = 0.81), glucagon (r = 0.88), cortisol (r = 0.87) and growth hormone (r = 0.76) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]Detailed reference viewed: 14 (0 ULg)