Measurement of insulin sensitivity by the minimal model method using a simplified intravenous glucose tolerance test: validity and reproducibility.
Duysinx, Bernard ; Scheen, André ; Gerard, Pascale et al
in Diabète & Métabolisme (1994), 20(4), 425-32
This study aimed at testing whether 12 rather than 26 plasma glucose and insulin determinations can be used to calculate the indices of insulin sensitivity and of glucose effectiveness using Bergman's ... [more ▼]
This study aimed at testing whether 12 rather than 26 plasma glucose and insulin determinations can be used to calculate the indices of insulin sensitivity and of glucose effectiveness using Bergman's minimal model during a simple intravenous glucose tolerance test performed without tolbutamide injection. Two intravenous glucose tolerance tests (separated by 1 week) were performed in 7 lean normal subjects and a single test was performed in 9 severely obese non-diabetic subjects. Intra-subject reproducibility of insulin sensitivity was not significantly different when 26 or 12 time-points were analyzed (CV = 16.8 +/- 3.4 versus 18.9 +/- 3.8% respectively). Compared with the insulin sensitivity of the lean subjects, that of obese subjects was significantly (P < 0.001) and similarly reduced when using 12 (2.14 +/- 0.34 versus 7.97 +/- 1.29 10(-4)min-1/mU.1-1) rather than 26 determinations (2.13 +/- 0.42 versus 6.95 +/- 1.12 10(-4) min-1/mU.1-1) respectively. Glucose effectiveness was less reproducible than insulin sensitivity and was slightly diminished by the reduction of blood samples (relative error: -9.7 +/- 4.4%; P < 0.05). Finally, glucose effectiveness tended to be slightly lower in the morbidly obese subjects than in the lean controls with both modes of calculation. In conclusion, in non-diabetic subjects, the insulin sensitivity index can be accurately measured during a simple intravenous glucose tolerance test, without tolbutamide injection and with only 12 blood samples. The possibility of performing a simplified test should contribute to increase the use of the minimal model method for estimating insulin sensitivity in clinical practice. [less ▲]Detailed reference viewed: 32 (2 ULg)
Epidemiology of insulin resistance and hypertension in adults - MONICA BELLUX- preliminary results.
Saint-Remy, Annie ; ; Lefèbvre, Pierre et al
in Cardiovascular Disease Epidemiology Newsletter, Amercian Heart Association (1994), 49
Numerous publications have outlined that insulin resistance, hypertension and obesity are often associated suggesting a common link in the pathogenic mechanisms.Detailed reference viewed: 42 (3 ULg)
Detection of early sympathetic cardiovascular neuropathy by squatting test in NIDDM.
; ; et al
in Diabetes Care (1994), 17(2), 149-51
OBJECTIVE--To determine the role of the squatting test in the detection of early sympathetic neuropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS--Three ... [more ▼]
OBJECTIVE--To determine the role of the squatting test in the detection of early sympathetic neuropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS--Three groups of nonsmoking, nonobese subjects were studied: 10 healthy subjects, 10 NIDDM patients without autonomic neuropathy (AN), and 10 NIDDM patients with AN defined by the presence of a pathological deep-breathing value. All subjects were given three postural tests: lying-to-standing, sitting-to-standing, and squatting test. Heart rate (HR) and finger arterial pressure were recorded with a noninvasive technique. RESULTS--Blood pressure (BP) fall (expressed as decremental area) was not significantly different among the groups at standing up after sitting or lying. By contrast, a significantly greater BP drop occurred in NIDDM patients with AN (1,123 +/- 245 mm2) compared with NIDDM patients without AN (460 +/- 232 mm2) or normal subjects (429 +/- 138 mm2, P < 0.001). The HR increase after all the orthostatic maneuvers was smaller in diabetic patients with AN (P < 0.01) compared with that recorded in other groups. Significant correlations were observed between BP fall after squatting and either the expiration:inspiration ratio at deep breathing (r = -0.77, P < 0.001) or the duration of diabetes (r = 0.76, P < 0.001). CONCLUSIONS--The intrinsic orthostatic load of the squatting test, which is greater than conventional postural maneuvers, makes the squatting test an easy and useful test to detect early orthostatic dysregulation in NIDDM. [less ▲]Detailed reference viewed: 24 (0 ULg)
Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type II) diabetic patients.
; Scheen, André ; et al
in Journal of Clinical Endocrinology and Metabolism (1994), 78(6), 1510-4
The aim of the present study was to investigate the effects of magnesium supplementation on glucose uptake and substrate oxidation in noninsulin-dependent (type II) diabetic patients. Nine elderly non ... [more ▼]
The aim of the present study was to investigate the effects of magnesium supplementation on glucose uptake and substrate oxidation in noninsulin-dependent (type II) diabetic patients. Nine elderly non-obese noninsulin-dependent (type II) diabetic patients, treated by diet only, participated in the study, which was designed as randomized, double blind, and cross-over. Each patient was followed up for a prestudy period of 3 weeks before inviting him/her to receive placebo or magnesium supplementation (15.8 mmol/day) for 4 weeks. At the end of each treatment period, a euglycemic hyperinsulinemic glucose clamp with simultaneous D-[3-3H]glucose infusion and indirect calorimetry was performed. Magnesium supplementation resulted in significantly increased plasma and erythrocyte magnesium levels, whereas body weight and fasting plasma glucose did not change. In the last 60 min of the glucose clamp, insulin-mediated glucose disappearance, total body glucose disposal (24.5 +/- 0.4 vs. 28.2 +/- 0.7 mumol/kg.min; P < 0.005), and glucose oxidation (13.0 +/- 0.4 vs. 16.3 +/- 0.8 mumol/kg.min; P < 0.01) were increased after chronic magnesium supplementation. Endogenous glucose production, nonoxidative glucose disposal, lipid and protein oxidation, and insulin MCR were not affected. In conclusion, a 4-week magnesium supplementation improves insulin sensitivity and glucose oxidation in the course of a euglycemic-hyperinsulinemic glucose clamp in noninsulin-dependent diabetic patients. Long term studies are needed to determine whether magnesium supplementation is useful in the management of type II diabetes. [less ▲]Detailed reference viewed: 24 (0 ULg)
Reduction of the acute bioavailability of metformin by the alpha-glucosidase inhibitor acarbose in normal man.
Scheen, André ; ; et al
in European Journal of Clinical Investigation (1994), 24 Suppl 3
In a double-blind cross-over study, we investigated a possible influence of the alpha-glucosidase inhibitor acarbose on the bioavailability of the biguanide compound metformin. Each of the six healthy ... [more ▼]
In a double-blind cross-over study, we investigated a possible influence of the alpha-glucosidase inhibitor acarbose on the bioavailability of the biguanide compound metformin. Each of the six healthy young male volunteers was randomly allocated during two consecutive 7 day periods to either acarbose (days 1-3: 3 x 50 mg day-1; days 4-7: 3 x 100 mg day-1) or placebo. At day 7 and 14 of the study, the overnight-fasted subjects ingested 1000 mg metformin with the first bite of a standardized breakfast (500 kcal; 60 g carbohydrates) and together with either placebo or 100 mg acarbose. Acarbose significantly (P < 0.05) reduced the meal-induced increase in blood glucose and plasma insulin levels. Acarbose induced a significant (P < 0.05) reduction in early (90, 120, 180 min) serum levels, peak concentrations (Cmax: 1.22 +/- 0.14 vs. 1.87 +/- 0.60 mg l-1) and area under the curve of metformin (AUC 0-540 min: 423 +/- 55 vs. 652 +/- 55 mg min l-1), but did not diminish its 24 h urinary excretion. In conclusion, acarbose significantly reduces the acute bioavailability of metformin in normal subjects. [less ▲]Detailed reference viewed: 35 (0 ULg)
The use of acarbose in the prevention and treatment of hypoglycaemia.
Lefebvre, Pierre ; Scheen, André
in European Journal of Clinical Investigation (1994), 24 Suppl 3
This paper reviews the use of acarbose in the prevention and treatment of hypoglycaemia. In diet- or sulfonylurea-treated patients, acarbose may reduce the incidence of late postprandial hypoglycaemia. In ... [more ▼]
This paper reviews the use of acarbose in the prevention and treatment of hypoglycaemia. In diet- or sulfonylurea-treated patients, acarbose may reduce the incidence of late postprandial hypoglycaemia. In insulin-treated patients, acarbose treatment usually requires reduction of the insulin dose; one study has shown that 100 mg acarbose at night significantly reduces the incidence of mid-evening and nocturnal hypoglycaemia. Several studies have suggested acarbose to be a useful adjunct to the management of reactive hypoglycaemia in the non-diabetic patients. Long-term prospective studies are still needed to document this last indication of acarbose or other alpha-glycosidase inhibitors. [less ▲]Detailed reference viewed: 67 (0 ULg)
Availability of glucose ingested during muscle exercise performed under acipimox-induced lipolysis blockade.
; Pirnay, Freddy ; Jandrain, Bernard et al
in European Journal of Applied Physiology and Occupational Physiology (1994), 68(5), 406-12
This study investigated the percentage of carbohydrate utilization than can be accounted for by glucose ingested during exercise performed after the ingestion of the potent lipolysis inhibitor Acipimox ... [more ▼]
This study investigated the percentage of carbohydrate utilization than can be accounted for by glucose ingested during exercise performed after the ingestion of the potent lipolysis inhibitor Acipimox. Six healthy male volunteers exercised for 3 h on a treadmill at about 45% of their maximal oxygen uptake, 75 min after having ingested 250 mg of Acipimox. After 15-min adaptation to exercise, they ingested either glucose dissolved in water, 50 g at time 0 min and 25 g at time 60 and 120 min (glucose, G) or sweetened water (control, C). Naturally labelled [13C]glucose was used to follow the conversion of the ingested glucose to expired-air CO2. Acipimox inhibited lipolysis in a similar manner in both experimental conditions. This was reflected by an almost complete suppression of the exercise-induced increase in plasma free fatty acid and glycerol and by an almost constant rate of lipid oxidation. Total carbohydrate oxidation evaluated by indirect calorimetry, was similar in both experimental conditions [C, 182, (SEM 21); G, 194 (SEM 16) g.3 h-1], as was lipid oxidation [C, 57 (SEM 6); G, 61 (SEM 3) g.3 h-1]. Exogenous glucose oxidation during exercise G, calculated by the changes in 13C:12C ratio of expired air CO2, averaged 66 (SEM 5) g.3 h-1 (19% of the total energy requirement). Consequently, endogenous carbohydrate utilization was significantly smaller after glucose than after placebo ingestion: 128 (SEM 18) versus 182 (SEM 21) g.3 h-1, respectively (P < 0.05). Symptoms of intense fatigue and leg cramps observed with intake of sweet placebo were absent with glucose ingestion.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]Detailed reference viewed: 35 (1 ULg)
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: 44 (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: 37 (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: 116 (1 ULg)
Les choix stratégiques actuels dans la prévention du processus diabétogène auto-immun
Geenen, Vincent ; Martens, Henri ; et al
in Médecine et Hygiène (1994), 52
Le diabète insulino-dépendant (DID) est de plus en plus admis comme résultant d'une rupture de la tolérance immunitaire vis-à-vis de la cellule ß pancréatique. La compréhension des mécanismes centraux et ... [more ▼]
Le diabète insulino-dépendant (DID) est de plus en plus admis comme résultant d'une rupture de la tolérance immunitaire vis-à-vis de la cellule ß pancréatique. La compréhension des mécanismes centraux et périphériques de la tolérance vis-à-vis de la cellule ß doit logiquement aboutir à une prévention non toxique et efficace du DID. Deux choix stratégiques sont proposés à l'heure actuelle. D'une part, la tolérance périphérique à l'insuline en tant que cible du processus auto-immun pourrait être restaurée via l'administration d'insuline à faibles doses par voie sous-cutanée ou orale. D'autre part, le facteur de croissance apparenté à l'insuline de type 2 (IGF2) pourrait réinduire la tolérance centrale de l'insuline et, secondairement, de la cellule ß insulino-sécrétrice. [less ▲]Detailed reference viewed: 25 (1 ULg)
Thymic neuroendocrine self peptides and T-cell selection
Geenen, Vincent ; Martens, Henri ; et al
in Heinen, Ernst; Defresne, Marie-Paule; Boniver, Jacques (Eds.) et al In Vivo Immunology - Regulatory Processes during Lymphopoiesis and Immunopoiesis (1994)Detailed reference viewed: 6 (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: 44 (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: 65 (2 ULg)
Evidence that insulin-like growth factor 2 (IGF2) is the dominant thymic peptide of the insulin superfamily
Geenen, Vincent ; ; et al
in Thymus (1993), 21(2), 115-127
Central T-cell tolerance of neurondocrine functions has been proposed to be primarily induced by the thymic repertoire of neuroendocrine self antigens. The present study aimed at characterizing the human ... [more ▼]
Central T-cell tolerance of neurondocrine functions has been proposed to be primarily induced by the thymic repertoire of neuroendocrine self antigens. The present study aimed at characterizing the human thymic insulin-related self antigen able to represent the pancreatic islet ß cell function in face of the developing T cells. Immunofluorescence studies were performed on human and rat thymic sections, as wess as on the rat IT-45R1 thymic epithelial cell line using several antibodies to epitopes of the insulin peptide family. These studies identify beyond any doubt that IGF2 is the dominant thymic peptide of the insulin family. The sequence of an insulin-derived autoantigen is proposed. This autoantigen is a nonamer and has a hydrophobic residue leucine at position 9. In human species, this autoantigen would primarily be tolerogenic for the pancreatic ß-cell endocrine function during fetal development. [less ▲]Detailed reference viewed: 78 (3 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: 18 (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: 30 (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: 27 (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: 35 (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: 35 (1 ULg)