Metabolic clearance rate of insulin in type 2 diabetic patients treated with combined insulin and sulfonylurea therapy.
; Scheen, André ; Lefebvre, Pierre
in Revista Espanola de Fisiologia (1994), 50(1), 27-34
The metabolic clearance rate of insulin (MCRI) in 10 non-obese type 2 diabetic patients treated with either insulin alone or combined insulin plus sulfonylurea therapy is investigated. A classical 2-hour ... [more ▼]
The metabolic clearance rate of insulin (MCRI) in 10 non-obese type 2 diabetic patients treated with either insulin alone or combined insulin plus sulfonylurea therapy is investigated. A classical 2-hour euglycaemic hyperinsulinaemic glucose clamp using the artificial pancreas was performed in a randomized order after two 6-week periods of treatment: either with subcutaneous injections of insulin alone or with insulin plus oral administration of the sulfonylurea compound glipizide at the dose of 3 x 10 mg/day. The MCRI was calculated knowing the constant insulin infusion rate (0.1 U.kg-1.h-1) and measuring basal and steady-state plasma free insulin and C-peptide levels. When the test was performed at the end of the period of treatment with insulin plus glipizide and 30 min after the ingestion of the last dose of 10 mg glipizide, plasma C-peptide levels were significantly increased and steady-state free insulin levels tended to be slightly higher whereas the metabolic clearance rate of glucose was not affected. The MCRI was significantly reduced by glipizide from 23.3 +/- 2.9 to 18.9 +/- 2.0 ml.kg-1.min-1 p < 0.05. These results demonstrate that the sulfonylurea glipizide decreases the MCRI. This effect may play a role in the hypoglycemic action of sulfonylureas. [less ▲]Detailed reference viewed: 35 (0 ULg)
Therapy for obesity--today and tomorrow.
Scheen, André ; Desaive, Claude ; Lefebvre, Pierre
in Bailliere's Clinical Endocrinology and Metabolism (1994), 8(3), 705-27
Obesity poses a serious health hazard and its treatment is often disappointing. Besides conservative methods, the place of pharmacotherapy, very-low-calorie diets, and even, in selected cases, mechanical ... [more ▼]
Obesity poses a serious health hazard and its treatment is often disappointing. Besides conservative methods, the place of pharmacotherapy, very-low-calorie diets, and even, in selected cases, mechanical means or surgery can be considered. Effective drug treatment for obesity must reduce energy intake, or increase energy expenditure, or increase energy losses in faeces. All these possibilities have potential activities but also serious limitations. Current pharmacotherapy essentially uses anorectic drugs and the other approaches, although promising, are still under investigation. Of the anorectic compounds currently available, serotoninergic agents, like dexfenfluramine and fluoxetine, appear to have the most suitable pharmacological profile. Very-low-calorie diets could help in the short-term but should be associated with other approaches to increase the rate of long-term success. They must be well-balanced as macronutrients and micronutrients are concerned, be prescribed in well-selected patients under careful medical supervision, and not be followed longer than a few weeks. Surgery can provide palliation for severe obesity when all medical approaches have failed. It may consist in decreasing food intake (gastric procedures), affecting calorie absorption (intestinal shunting, biliopancreatic bypass), or removing localized excess fat (lipectomy, liposuction). Gastric reduction operations are safe and effective provided they are performed by experienced surgeons in well-selected patients. They can be considered now as the best option for a minority of patients with morbid and refractory obesity. Finally, in very selected patients, mechanical means (such as the waist cord) may also help losing weight and/or avoiding weight regain. Even if all these therapeutic approaches can be helpful, at least in some obese individuals, they also have important limitations so that prevention remains up to now the 'treatment' of choice for obesity. [less ▲]Detailed reference viewed: 36 (0 ULg)
Magnesium et metabolisme glucidique.
Lefebvre, Pierre ; ; Scheen, André
in Thérapie (1994), 49(1), 1-7
The interrelationships between magnesium and carbohydrate metabolism have regained considerable interest over the last few years. Insulin secretion requires magnesium: magnesium deficiency results in ... [more ▼]
The interrelationships between magnesium and carbohydrate metabolism have regained considerable interest over the last few years. Insulin secretion requires magnesium: magnesium deficiency results in impaired insulin secretion while magnesium replacement restores insulin secretion. Furthermore, experimental magnesium deficiency reduces the tissues sensitivity to insulin. Subclinical magnesium deficiency is common in diabetes. It results from both insufficient magnesium intakes and increase magnesium losses, particularly in the urine. In type 2, or non-insulin-dependent, diabetes mellitus, magnesium deficiency seems to be associated with insulin resistance. Furthermore, it may participate in the pathogenesis of diabetes complications and may contribute to the increased risk of sudden death associated with diabetes. Some studies suggest that magnesium deficiency may play a role in spontaneous abortion of diabetic women, in fetal malformations and in the pathogenesis of neonatal hypocalcemia of the infants of diabetic mothers. Administration of magnesium salts to patients with type 2 diabetes tend to reduce insulin resistance. Long-term studies are needed before recommending systematic magnesium supplementation to type 2 diabetic patients with subclinical magnesium deficiency. [less ▲]Detailed reference viewed: 114 (1 ULg)
Relationships between metabolic clearance rate of insulin and body mass index in a female population ranging from anorexia nervosa to severe obesity.
; Scheen, André ; Jandrain, Bernard et al
in International Journal of Obesity & Related Metabolic Disorders (1994), 18(1), 47-53
Changes in the metabolic clearance rate of insulin (MCRI) have been described in several pathological conditions. Conflicting data suggest that they may be related to either body mass index (BMI) or body ... [more ▼]
Changes in the metabolic clearance rate of insulin (MCRI) have been described in several pathological conditions. Conflicting data suggest that they may be related to either body mass index (BMI) or body composition. This study aimed to investigate the relationship between the MCRI and BMI in an exclusively female population showing a wide range of BMI. For that purpose, hyperinsulinemic normoglycemic glucose clamps were performed in nine anorectic subjects (BMI: 14.5 +/- 0.8 kg/m2), 11 healthy volunteers (BMI: 20.3 +/- 0.5 kg/m2) and 12 obese patients (BMI: 33.0 +/- 0.9 kg/m2). To exclude any influence of the menstrual cycle on the MCRI, five healthy women underwent three tests at different days of the menstrual cycle: menstruation period, late follicular pre-ovulatory phase and luteal phase, in random order. The MCRI, which was quite reproducible in a given subject, was not significantly modified by the menstrual cycle. In the premenopausal female population studied, the mean (+/- s.e.m.) MCRI normalized for body weight (kg) were 35.4 +/- 3.4, 24.7 +/- 1.8 and 14.0 +/- 1.0 ml/kg/min (P < 0.01) for anorectic subjects, healthy volunteers and obese patients, respectively. These differences were maintained when the MCRI was normalized according to corporeal surface (m2) (1018 +/- 75, 859 +/- 67, 638 +/- 40 ml/m2/min, P < 0.01) or lean body mass (kg) (37.1 +/- 3.4, 32.6 +/- 2.7 and 24.1 +/- 0.5 ml/kgLBM/min, P < 0.01), but disappeared when MCRI was expressed per kg of ideal body weight (24.6 +/- 2.2, 24.6 +/- 2.1 and 22.4 +/- 1.4 ml/kgIBW/min, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]Detailed reference viewed: 35 (1 ULg)
Insulin secretion, clearance and action before and after gastroplasty in severely obese subjects.
Letiexhe, Michel ; Scheen, André ; Gerard, Pascale et al
in International Journal of Obesity & Related Metabolic Disorders (1994), 18(5), 295-300
This study investigated the effects of a drastic weight reduction on insulin secretion rate (ISR), insulin metabolic clearance rate (MCRI) and insulin sensitivity (SI) in severely obese subjects. A ... [more ▼]
This study investigated the effects of a drastic weight reduction on insulin secretion rate (ISR), insulin metabolic clearance rate (MCRI) and insulin sensitivity (SI) in severely obese subjects. A frequently sampled intravenous glucose tolerance test (FSIVGTT, 0.3 g/kg) was performed before and 8 +/- 1 months after a vertical ring gastroplasty in 12 overnight-fasted obese non-diabetic subjects; the results were compared to those obtained in 12 lean controls matched for age and sex. ISR was derived by deconvolution of plasma C-peptide levels; MCRI was obtained by dividing the area under the curve (AUC180 min) of ISR by the corresponding AUC of plasma insulin levels (IRI); the SI and the glucose effectiveness index (SG) were calculated by Bergman's minimal model. Before gastroplasty, obese subjects showed significantly higher ISR (P < 0.02), lower MCRI (P < 0.001), lower SI (P < 0.001) but similar SG when compared to lean controls. After gastroplasty (reduction of body weight from 104.8 +/- 3.8 to 73.4 +/- 3.6 kg and of BMI from 37.9 +/- 0.8 to 26.5 +/- 0.9 kg/m2; P < 0.001), ISR only decreased from 53,125 +/- 7968 to 42,302 +/- 3716 pmol/180 min (not significant) while AUC-IRI dramatically fell from 53,626 +/- 6378 to 21,111 +/- 2584 pmol.min/l; P < 0.001); consequently, MCRI markedly increased from 526 +/- 96 to 1257 +/- 150 ml/min/m2; P < 0.01). SI significantly rose from 3.12 +/- 0.45 to 7.10 +/- 1.20 x 10(-4) l/mU/min (P < 0.005) while SG remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]Detailed reference viewed: 62 (2 ULg)
Hyperlipidemies et medicaments hypolipidemiants.
Scheen, André ; Paquot, Nicolas
in Journal de Pharmacie de Belgique (1993), 48(2), 92-101
Hyperlipidaemia, as a primary atherogenic risk factor, represents a major problem of public health. This review first reminds the main steps of lipoprotein metabolism, the classification of the most ... [more ▼]
Hyperlipidaemia, as a primary atherogenic risk factor, represents a major problem of public health. This review first reminds the main steps of lipoprotein metabolism, the classification of the most frequent hyperlipidaemias, the objectives of the treatment and the required initial evaluation allowing to decide how to manage the patient. Thereafter, it describes all the available treatments, more particularly the characteristics of the various lipid lowering drugs. Finally, it proposes a step by step strategy for the treatment of the main hyperlipidaemias and summarizes the managements of some particular cases. [less ▲]Detailed reference viewed: 50 (0 ULg)
Feasability and reproductibility of the minimal model method to measure insulin sensitivity in lean and obese non-diabetic subjects.
SCHEEN, André ; ; LETIEXHE, Michel et al
Poster (1993)Detailed reference viewed: 11 (1 ULg)
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: 29 (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: 23 (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: 26 (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: 32 (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)