Effects of moderate versus marked weight loss on insulin sensitivity and androgenic markers in obese women
LETIEXHE, Michel ; SCHEEN, André ; PAQUOT, Nicolas et al
in International Journal of Obesity (1993), 17(suppl 2), 96Detailed reference viewed: 22 (2 ULg)
Effects of insulin therapy in insulin-requiring type 2 diabetic patients.
DUYSINX, Bernard ; SCHEEN, André ; PAQUOT, Nicolas et al
in Acta Clinica Belgica (1993), 48Detailed reference viewed: 8 (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: 23 (1 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: 22 (1 ULg)
Effects of moderate vs marked weight loss on insulin sensitivity and androgenic markers in obese women
LETIEXHE, Michel ; SCHEEN, André ; PAQUOT, Nicolas et al
in Ditschuneit, H.; Gries, F. A.; Hauner, H. (Eds.) et al Obesity in Europe (1993)Detailed reference viewed: 17 (0 ULg)
Combination of oral antidiabetic drugs and insulin in the treatment of non-insulin-dependent diabetes.
Scheen, André ; ; Lefebvre, Pierre
in Acta Clinica Belgica (1993), 48(4), 259-68
Non-insulin-dependent diabetes mellitus (NIDDM) appears to be an heterogeneous disorder characterized by both relative insulin deficiency and impaired insulin action. The initial management of NIDDM ... [more ▼]
Non-insulin-dependent diabetes mellitus (NIDDM) appears to be an heterogeneous disorder characterized by both relative insulin deficiency and impaired insulin action. The initial management of NIDDM should include patient education, dietary counselling and individualized programs of physical activity. It is only when such measures fail that drug therapy should be considered. Oral drug therapies include sulphonylurea derivatives, biguanides, among which metformin remains the only one commercialized in our country, and alpha-glucosidase inhibitors such as acarbose. However, insulin therapy may be required to achieve adequate glycaemic control in some patients, the so-called secondary failures to oral treatment. The rationale for combining insulin and oral drug therapy derives from a better understanding of the pathophysiology of NIDDM and of the mechanisms of action of the oral drugs available: 1) type 2 diabetic patients are both insulin-deficient and insulin-resistant, thus requiring quite high doses of exogenous insulin; 2) peripheral insulin delivery leads to hyperinsulinaemia which could play a role in the pathogenesis of late diabetic complications; 3) sulphonylureas stimulate insulin release directly into the portal vein and could also potentiate peripheral insulin action; and 4) metformin (by improving glucose metabolism and insulin sensitivity) and alpha-glucosidase inhibitors (by slowing down the digestion of complex carbohydrates and sucrose) are able to reduce the amounts of insulin needed to control postprandial hyperglycaemia. Numerous studies have shown that a combination of insulin and sulphonylurea is more effective than insulin alone in the treatment of patients with NIDDM after secondary failure to oral drugs, leading to better glucose profiles and/or decreased insulin needs. The available data suggest that combination therapy is most beneficial in the diabetic patient who still has residual insulin secretory capacity and that the best scheme comprises an evening injection of lente insulin and the administration of sulphonylureas before meals. Preliminary results suggested that insulin-metformin (when obesity is present) or insulin-acarbose (when post-prandial hyperglycaemia occurs) combinations might offer some favourable features for the treatment of NIDDM patients although these therapeutical approaches still require adequate evaluation in further controlled studies. The additional cost of such combined therapy should be weighed against the potential advantages of better metabolic control. [less ▲]Detailed reference viewed: 28 (0 ULg)
Endogenous substrate oxidation during exercise and variations in breath 13CO2/12CO2.
; Pirnay, Freddy ; Jandrain, Bernard et al
in Journal of Applied Physiology (Bethesda, Md. : 1985) (1993), 74(1), 133-8
This study attempted to induce a major shift in the utilization of endogenous substrates during exercise in men by the use of a potent inhibitor of adipose tissue lipolysis, Acipimox, and to see to what ... [more ▼]
This study attempted to induce a major shift in the utilization of endogenous substrates during exercise in men by the use of a potent inhibitor of adipose tissue lipolysis, Acipimox, and to see to what extent this affects the 13C/12C ratio in expired air CO2. Six healthy volunteers exercised for 3 h on a treadmill at approximately 45% of their maximum O2 uptake, 75 min after having ingested either a placebo or 250 mg Acipimox. The rise in plasma free fatty acids and glycerol was almost totally prevented by Acipimox, and no significant rise in the utilization of lipids, evaluated by indirect calorimetry, was observed. Total carbohydrate oxidation averaged 128 +/- 17 (placebo) and 182 +/- 21 g/3 h (Acipimox). Conversely, total lipid oxidation was 84 +/- 5 (placebo) and 57 +/- 6 g/3 h (Acipimox; P < 0.01). Under placebo, changes in expired air CO2 delta 13C were minimal, with only a 0.49/1000 significant rise at 30 min. In contrast, under Acipimox, the rise in expired air CO2 delta 13C averaged 1/1000 and was significant throughout the 3-h exercise bout; in these conditions calculation of a "pseudooxidation" of an exogenous sugar naturally or artificially enriched in 13C, but not ingested, would have given an erroneous value of 19.8 +/- 2.6 g/3 h. Thus under conditions of extreme changes in endogenous substrate utilization, an appropriate control experiment is mandatory when studying exogenous substrate oxidation by 13C-labeled substrates and isotope-ratio mass spectrometry measurements on expired air CO2. [less ▲]Detailed reference viewed: 22 (1 ULg)
Effects of a 1-year treatment with a low-dose combined oral contraceptive containing ethinyl estradiol and cyproterone acetate on glucose and insulin metabolism.
Scheen, André ; Jandrain, Bernard ; Humblet, Dominique et al
in Fertility and Sterility (1993), 59(4), 797-802
OBJECTIVE: To study the effects of the slightly estrogen-dominant monophasic low-dose oral contraceptive (OC) Diane-35 (Schering AG, Berlin, Germany) (35 micrograms ethinyl estradiol [EE2] + 2 mg ... [more ▼]
OBJECTIVE: To study the effects of the slightly estrogen-dominant monophasic low-dose oral contraceptive (OC) Diane-35 (Schering AG, Berlin, Germany) (35 micrograms ethinyl estradiol [EE2] + 2 mg cyproterone acetate, a 17 alpha-hydroxyprogesterone derivative [17-OHP]) on glucose and insulin metabolism. DESIGN: Seven healthy young women were investigated by using the euglycemic hyperinsulinemic glucose clamp technique (insulin delivery rate = 100 mU/kg per hour for 120 minutes). This test was performed, after an overnight fast, during the last 7 days of a spontaneous cycle and within the last 5 days of pill intake during the sixth and twelfth cycle of a continuous treatment with Diane-35 in each subject. RESULTS: The three indexes measuring the insulin-induced glucose disposal during the clamp (glucose infusion rate, glucose metabolic clearance rate, and glucose infusion rate divided by plasma insulin plateau levels) were not significantly affected by Diane-35. In contrast, the metabolic clearance rate of the exogenous insulin infused during the clamp tended to be slightly increased with Diane-35 (significant after 6 but not after 12 cycles). CONCLUSION: These results suggest that a 1-year treatment with the OC Diane-35, which contains EE2 + a 17-OHP rather than a 19-nortestosterone derivative as the progestogen compound, does not significantly alter peripheral (presumably muscular) insulin sensitivity but slightly increases insulin (presumably hepatic) clearance. [less ▲]Detailed reference viewed: 25 (0 ULg)
Fructose utilization during exercise in men: rapid conversion of ingested fructose to circulating glucose.
Jandrain, Bernard ; ; et al
in Journal of Applied Physiology (Bethesda, Md. : 1985) (1993), 74(5), 2146-54
The aim of the present study was to compare the metabolic fate of repeated doses of fructose or glucose ingested every 30 min during long-duration moderate-intensity exercise in men. Healthy volunteers ... [more ▼]
The aim of the present study was to compare the metabolic fate of repeated doses of fructose or glucose ingested every 30 min during long-duration moderate-intensity exercise in men. Healthy volunteers exercised for 3 h on a treadmill at 45% of their maximal oxygen consumption rate. "Naturally labeled" [13C]glucose or [13C]fructose was given orally at 25-g doses every 30 min (total feeding: 150 g; n = 6 in each group). Substrate utilization was evaluated by indirect calorimetry, and exogenous sugar oxidation was measured by isotope ratio mass spectrometry on expired CO2. Results were corrected for baseline drift in 13C/12C ratio in expired air due to exercise alone. Fructose conversion to plasma glucose was measured combining gas chromatography and isotope ratio mass spectrometry. Most of the ingested glucose was oxidized: 81 +/- 4 vs. 57 +/- 2 g/3 h for fructose (2P < 0.005). Exogenous glucose covered 20.8 +/- 1.4% of the total energy need (+/- 6.7 MJ) compared with 14.0 +/- 0.6% for fructose (2P < 0.005). The contribution of total carbohydrates was significantly higher and that of lipids significantly lower with glucose than with fructose. The blood glucose response was similar in both protocols. From 90 to 180 min, 55-60% of circulating glucose was derived from ingested fructose. In conclusion, when ingested repeatedly during moderate-intensity prolonged exercise, fructose is metabolically less available than glucose, despite a high rate of conversion to circulating glucose. [less ▲]Detailed reference viewed: 21 (0 ULg)
Insulin secretion, clearance, and action on glucose metabolism in cirrhotic patients.
Letiexhe, Michel ; Scheen, André ; Gerard, Pascale et al
in Journal of Clinical Endocrinology and Metabolism (1993), 77(5), 1263-8
To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test ... [more ▼]
To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test (0.3 g glucose/kg BW) in nine compensated cirrhotic patients and nine healthy volunteers well matched for age, sex, and body weight. The insulin secretion rate was derived by the deconvolution of plasma C-peptide levels, insulin sensitivity was calculated using Bergman's minimal model method, and insulin clearance was estimated by dividing the 0-180 min area under the curve of insulin secretion rate by that of peripheral plasma insulin levels. The cirrhotic patients were characterized during the frequently sampled i.v. glucose tolerance test by a 60% greater insulin secretion rate (P < 0.05), a markedly reduced insulin sensitivity index (SI; 2.82 +/- 0.75 vs. 5.86 +/- 0.68 x 10(-4) min/mU.L; P < 0.01) and a 40% reduced insulin clearance (725 +/- 169 vs. 1165 +/- 99 mL/min.m-2; P < 0.05). The reduction of insulin clearance was significantly correlated with the amplitude of the portosystemic shunt, measured using an isotopic method (r = 0.75; P < 0.02). In conclusion, cirrhosis is characterized by an important peripheral hyperinsulinism, resulting from both a higher insulin secretion rate and a reduced insulin hepatic clearance; the severe insulin resistance explains the glucose metabolism alterations. [less ▲]Detailed reference viewed: 31 (1 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: 16 (0 ULg)
Unchanged insulin secretion after an acute moderate weight reduction in non- diabetic obese subjects.
SCHEEN, André ; Paquot, Nicolas ; et al
in International Journal of Obesity (1992, May), 35(29 (suppl)), 116Detailed reference viewed: 13 (0 ULg)
La neuropathie périphérique et autonome chez les patients diabétiques: corrélation avec la clinique, la durée du diabète et les complications oculaires
; ; Foidart-Dessalle, Marguerite et al
in Revue Médicale de Liège (1992), 47(5), 245-54Detailed reference viewed: 55 (7 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: 66 (7 ULg)
Approches thérapeutiques des anomalies de la boucle de régulation glucose-insuline chez le patient diabétique.
SCHEEN, André ; PAQUOT, Nicolas ;
in Médecine et Hygiène (1992), 50Detailed reference viewed: 2 (0 ULg)
Approches thérapeutiques des hyperlipidémies associées aux pathologies rénales.
PAQUOT, Nicolas ; SCHEEN, André ; DECHENNE, Charles et al
in Médecine et Hygiène (1992), 50Detailed reference viewed: 7 (0 ULg)
Acute functional iron deficiency in obese subjects during very-low-energy all- protein diet.
; BEGUIN, Yves ; et al
Poster (1992)Detailed reference viewed: 12 (1 ULg)
Insulin secretion and action in various populations with type 2 (non-insulin-dependant) diabetes mellitus
Scheen, André ; ; et al
in Diabetologia (1992), 16 ( suppl 1)(29), 116Detailed reference viewed: 10 (0 ULg)
Improvement of the metabolic clearance rate of insulin after a protein-supplemented fast in obese subjects.
PAQUOT, Nicolas ; SCHEEN, André ; et al
in International Journal of Obesity (1992)Detailed reference viewed: 13 (0 ULg)
Management of non-insulin-dependent diabetes mellitus.
Lefebvre, Pierre ; Scheen, André
in Drugs (1992), 44 Suppl 3
The initial management of non-insulin-dependent diabetes mellitus (NIDDM) should include patient education, dietary counselling and, when feasible, individualised physical activity. It is only when such ... [more ▼]
The initial management of non-insulin-dependent diabetes mellitus (NIDDM) should include patient education, dietary counselling and, when feasible, individualised physical activity. It is only when such measures fail that drug therapy should be considered. Dietary management of NIDDM includes a restriction in calories, and these should be appropriately distributed as carbohydrates, lipids and proteins. Supplementation of the diet with soluble fibre and supplementation with magnesium salts if hypomagnesaemia is demonstrated, is recommended. However, supplementation with fish oils or with fish oil-derived omega-3 fatty acids is not currently recommended. Oral drug therapies used in NIDDM include sulphonylurea derivatives, which are a first-line treatment in patients who are not grossly obese, metformin, which is the treatment of choice for obese patients, and alpha-glucosidase inhibitors such as acarbose, which are used mainly to reduce postprandial blood glucose peaks. These types of drugs can be used alone or in combination. Insulin therapy may be required to achieve adequate control of blood glucose levels in some patients. In several instances, it is suggested that insulin therapy be combined with sulphonylureas (essentially when residual insulin secretion is present), with metformin, or with alpha-glucosidase inhibitors. The treatment of disorders associated with NIDDM, such as obesity, hypertension or hyperlipidaemia, requires particular attention in diabetic patients, since some drugs can adversely affect glycaemic control. Oral drugs for the treatment of NIDDM include sulphonylurea derivatives used in first-line treatment in patients who are not grossly obese, metformin, which is often the treatment of choice for obese patients and, more recently, the alpha-glucosidase inhibitors, such as acarbose, which are effective in reducing the postprandial rise in blood glucose. [less ▲]Detailed reference viewed: 73 (1 ULg)