The role of the thymus in T cell self-tolerance of neuroendocrine principles and in development of neuroendocrine autoimmunity
Geenen, Vincent ; ; Lefebvre, Pierre et al
in Journal of Neuroimmunology (2001), 118Detailed reference viewed: 9 (2 ULg)
Obesity: causes and new treatments.
Lefebvre, Pierre ; Scheen, André
in Experimental & Clinical Endocrinology & Diabetes (2001), 109 Suppl 2
The prevalence of obesity increases rapidly in developed and developing countries. Obesity results from a cumulative positive energy balance and is favoured by both genetic and environmental factors ... [more ▼]
The prevalence of obesity increases rapidly in developed and developing countries. Obesity results from a cumulative positive energy balance and is favoured by both genetic and environmental factors. Preventing obesity requires a major investment in nutritional and lifestyle education, particularly in children and adolescents.--The pharmacological approach to obesity includes drugs that reduce food intake (noradrenergic and serotoninergic agents), drugs that increase energy expenditure and compounds that affect nutrient partitioning. In all instances, the benefit-to-risk ratio needs to be carefully assessed. In some patients (severe obesity or obesity accompanied by serious high-risk comorbid conditions), gastric surgery (gastric restriction or gastric bypass) should be considered. In our own experience, it is safe and effective. [less ▲]Detailed reference viewed: 41 (0 ULg)
Risk of Developiment and progression of retinopathy in Diabetes Control and Complications Trial Type 1 Diabetic Patients With Good or Poor Metabolic Control
; ; Albert, Adelin et al
in Diabete (Le) (2000)Detailed reference viewed: 12 (0 ULg)
Recommandations a propos du traitement de l'hypertension arterielle chez le patient diabetique.
Scheen, André ; Rorive, Marcelle ; et al
in Revue Médicale de Liège (2000), 55(5), 376-82
Diabetes mellitus is frequently associated with arterial hypertension and the combination of the two entities markedly increases the cardiovascular risk and accelerates the progression of microangiopathy ... [more ▼]
Diabetes mellitus is frequently associated with arterial hypertension and the combination of the two entities markedly increases the cardiovascular risk and accelerates the progression of microangiopathy (more particularly nephropathy) in both type 1 and type 2 diabetic patients. Numerous international guidelines have been published during the last few years to help the practitioner in targeting ideal arterial blood pressure levels (lower in diabetic than in non-diabetic patients) and in selecting first-choice antihypertensive agents. We will concisely summarize the main messages of these recommendations and insist upon the persistence of uncertainties, or even the existence of inconsistencies, more particularly regarding preferential indications of antihypertensive agents in diabetic patients. [less ▲]Detailed reference viewed: 58 (1 ULg)
Autonomic dysfunction evidenced by a squatting test in type 1 diabetic patients: effect of disease duration.
SCHEEN, André ; ; PHILIPS, Jean-Christophe et al
in Diabetologia (2000), 43(supp), 279Detailed reference viewed: 9 (0 ULg)
Assessment of postprandial hepatic glycogen synthesis from uridine diphosphoglucose kinetics in obese and lean non-diabetic subjects.
Paquot, Nicolas ; ; Scheen, André et al
in International Journal of Obesity & Related Metabolic Disorders (2000), 24(10), 1297-302
BACKGROUND: Obese patients are frequently characterized by insulin resistance and decreased insulin-mediated glycogen synthesis in skeletal muscle. Whether they also have impaired postprandial hepatic ... [more ▼]
BACKGROUND: Obese patients are frequently characterized by insulin resistance and decreased insulin-mediated glycogen synthesis in skeletal muscle. Whether they also have impaired postprandial hepatic glycogen synthesis remains unknown. AIM: To determine whether postprandial hepatic glycogen synthesis is decreased in obese patients compared to lean subjects. METHODS: Lean and obese subjects with impaired glucose tolerance were studied over 4h after ingestion of a glucose load. Hepatic uridine diphosphoglucose kinetics were assessed using 13C-galactose infusion, with monitoring of urinary acetaminophen-glucuronide isotopic enrichment to estimate hepatic glycogen kinetics. RESULTS: Estimated net hepatic glycogen synthesis amounted to 18.6 and 22.6% of the ingested load in lean and obese subjects, respectively. CONCLUSION: Postprandial hepatic glycogen metabolism is not impaired in non-diabetic obese subjects. [less ▲]Detailed reference viewed: 32 (1 ULg)
No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients.
Paquot, Nicolas ; ; Lefebvre, Pierre et al
in Journal of Clinical Endocrinology and Metabolism (2000), 85(3), 1316-9
Inhibition of tumor necrosis factor (TNF)-alpha results in a marked increase in insulin sensitivity in obese rodents. We investigated the influence of a TNF antagonist [Ro 45-2081, a recombinant fusion ... [more ▼]
Inhibition of tumor necrosis factor (TNF)-alpha results in a marked increase in insulin sensitivity in obese rodents. We investigated the influence of a TNF antagonist [Ro 45-2081, a recombinant fusion protein that consists of the soluble TNF-receptor (p55) linked to the Fc portion of human IgG1] on insulin sensitivity of patients with android obesity. Seven patients (five women and two men; mean +/- SD age, 41 +/- 4 yr; body mass index, 36.1 +/- 4.7 kg/m2; waist to hip ratio, 0.99 +/- 0.11) were studied (three patients with normal glucose tolerance and four patients with impaired glucose tolerance or mild diabetes; all were hyperinsulinemic). Each patient underwent two consecutive euglycemic hyperinsulinemic glucose-clamp tests: 48 h after injection of placebo and 48 h after a single i.v. injection of 50 mg Ro 45-2081. In both tests, steady-state plasma glucose and insulin levels were similar. Insulin-mediated glucose disposal (2.23 +/- 0.74 vs. 2.38 +/- 0.99 mg/kg(-1) x min(-1)) and glucose metabolic clearance rate (2.28 +/- 0.85 vs. 2.48 +/- 1.03 mL/kg(-1) x min(-1)) were similar after placebo and after the drug. Indirect calorimetry showed no difference in substrate oxidation rates between the two experimental conditions. In conclusion, under the conditions of this study, no improvement in insulin sensitivity was observed in obese insulin-resistant patients following a single i.v. administration of a recombinant TNF receptor: Fc fusion protein. [less ▲]Detailed reference viewed: 4 (0 ULg)
Thymic insulin-related genes: role in T-lymphocyte development and self-tolerance of the insulin family
; Martens, Henri ; et al
in Pflügers Archiv : European Journal of Physiology (2000), 440Detailed reference viewed: 4 (0 ULg)
Antiobesity pharmacotherapy in the management of type 2 diabetes.
Scheen, André ; Lefebvre, Pierre
in Diabetes/Metabolism Research & Reviews (2000), 16(2), 114-24
Obesity is a well-known risk factor for the development of Type 2 diabetes mellitus. The management of the obese diabetic patient remains a challenge for the clinician but, in any case, weight reduction ... [more ▼]
Obesity is a well-known risk factor for the development of Type 2 diabetes mellitus. The management of the obese diabetic patient remains a challenge for the clinician but, in any case, weight reduction should be considered as a key objective. In this respect, several antiobesity drugs have demonstrated potential. However, while fenfluramine and dexfenfluramine have been shown to promote weight loss and to directly improve insulin sensitivity, being two mechanisms contributing to better blood glucose control in obese Type 2 diabetic patients, they were recently withdrawn due to safety problems. Sibutramine, a new selective norepinephrine and serotonin reuptake inhibitor, promotes weight loss by decreasing food intake, an effect which leads to a mild improvement (significant in patients losing > or =5% of initial body weight) of blood glucose control in obese diabetic patients. Similarly, orlistat, a selective gastrointestinal lipase inhibitor which increases faecal fat losses, enhances diet-induced weight reduction and improves both blood glucose control and vascular risk profile, especially dyslipidaemia, in obese Type 2 diabetic patients. Further studies are required to better identify good responders to pharmacotherapy and specify the role of antiobesity agents in the overall long-term management of obese subjects with Type 2 diabetes. Other novel pharmacological approaches deserve further consideration, for instance beta-3 agonists aiming to increase energy expenditure, drugs interfering with tumor necrosis factor-alpha (TNF-alpha) or free fatty acid release by the adipose tissue or agents that slow gastric emptying. However, until now, results regarding efficacy and/or safety have been disappointing or preliminary in humans. [less ▲]Detailed reference viewed: 22 (0 ULg)
Non-alcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss.
Luyckx, Françoise ; Lefebvre, Pierre ; Scheen, André
in Diabètes & Métabolism (2000), 26(2), 98-106
Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance, and is now considered as one of the commonest liver diseases in western countries. It is frequently associated with ... [more ▼]
Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance, and is now considered as one of the commonest liver diseases in western countries. It is frequently associated with severe obesity, especially abdominal adiposity, and is intimately related to various clinical and biological markers of the insulin resistance syndrome. Especially, both the prevalence and the severity of liver steatosis are related to male sex, body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. A substantial weight loss following gastroplasty is accompanied by a marked reduction in the prevalence and the severity of the various biological abnormalities of the metabolic syndrome and, concomitantly, by an important regression of liver steatosis in most obese patients. However, in some patients, this rapid and drastic weight loss may result in a mild increase in inflammatory lesions (hepatitis), despite the regression of steatosis, which might result from the rapid mobilization of fatty acids or cytokines from adipose tissue, especially visceral fat. The intimate relationship between NASH and obesity leads to the concept that NASH may be considered as another disease of affluence, as is the insulin resistance syndrome and perhaps being part of it. [less ▲]Detailed reference viewed: 33 (2 ULg)
Developpement et utilisation d'un systeme de telemedecine pour le suivi medical des patients diabetiques.
; ; et al
in Journées Annuelles de Diabetologie de l'Hôtel-Dieu (2000)Detailed reference viewed: 42 (0 ULg)
Relationship between incipiens nephropathy and cardiac autonomic neuropathy in type 1 diabetes
; Scheen, André ; et al
in Diabetes (2000), 49(sup. 1), 379-380Detailed reference viewed: 19 (0 ULg)
Le controle glycemique chez le patient diabetique. Recommandations apres les etudes DCCT et UKPDI.
Paquot, Nicolas ; Scheen, André ; Lefebvre, Pierre
in Revue Médicale de Liège (2000), 55(5), 372-5
Diabetes mellitus is a chronic disorder characterized by microvascular and cardiovascular complications that substantially increase the morbidity and mortality associated with the disease. Several studies ... [more ▼]
Diabetes mellitus is a chronic disorder characterized by microvascular and cardiovascular complications that substantially increase the morbidity and mortality associated with the disease. Several studies showed the association between the complications of diabetes and elevated blood glucose levels. Clinical trials have also demonstrated that treatment that lowers blood glucose reduces the risks of diabetic complications (mainly microvascular complications). The control of diabetes is assessed by frequent measurements of HbA1c. A reasonable goal in type 1 diabetes is a value of HbA1c < or = 7.2%. In type 2 diabetes, the optimal goal is a value of HbA1c < or = 6.5%, but a value < or = 8% seems to be an acceptable goal in these patients. [less ▲]Detailed reference viewed: 25 (0 ULg)
Thymic insulin-related polypeptides in diabetes-prone Bio-Breeding rats
; Winkler, Rose ; Martens, Henri et al
in Diabetologia (1999), 42 (Suppl. 1)Detailed reference viewed: 22 (1 ULg)
Parallel reversibility of biological markers of the metabolic syndrome and liver steatosis after gastroplasty-induced weight loss in severe obesity.
Luyckx, Françoise ; Scheen, André ; Desaive, Claude et al
in Journal of Clinical Endocrinology and Metabolism (1999), 84(11), 4293Detailed reference viewed: 5 (2 ULg)
Glucose metabolism and the postprandial state.
Lefebvre, Pierre ; Scheen, André
in European Journal of Clinical Investigation (1999), 29 Suppl 2
Disturbances of postprandial glucose metabolism are now thought to contribute to cardiovascular disease. Postprandial glucose excursions can be affected by a number of factors, such as the types of ... [more ▼]
Disturbances of postprandial glucose metabolism are now thought to contribute to cardiovascular disease. Postprandial glucose excursions can be affected by a number of factors, such as the types of carbohydrates ingested and the way they are metabolized. In Type 2 diabetes, factors that contribute to excessive postprandial glucose excursions include disruption of insulin secretion, insufficient inhibition of hepatic glucose production and defective glucose storage in muscle. A number of measures may attenuate excessive postprandial blood glucose excursions. These include a diet high in 'low glycaemic index' foods and treatment with drugs that improve or restore the hormonal response (e.g. the sulphonylureas and the newer beta-cell mediated insulinotropic drugs such as repaglinide), that improve insulin sensitivity or that delay gastric emptying. [less ▲]Detailed reference viewed: 19 (0 ULg)
Severe/extreme obesity: a medical disease requiring a surgical treatment?
Scheen, André ; Luyckx, Françoise ; Desaive, Claude et al
in Acta Clinica Belgica (1999), 54(3), 154-61
Obesity poses a serious health hazard and its treatment is often disappointing. Surgical approaches have been proposed for treating severe obesity (body mass index or BMI > or = 35 kg/m2) with ... [more ▼]
Obesity poses a serious health hazard and its treatment is often disappointing. Surgical approaches have been proposed for treating severe obesity (body mass index or BMI > or = 35 kg/m2) with comorbidities or extreme obesity (BMI > or = 40 kg/m2). Before accepting bariatric surgery as alternative treatment, the four following prerequisites should be met: 1. the medical condition is serious enough; 2. it can not be treated satisfactorily with classical means; 3. the surgical treatment is effective in improving the clinical situation; and 4. bariatric surgery is safe enough, so that the benefits clearly outweigh the risks. On the basis of the literature and our own experience, it appears that gastric reduction surgery may be considered as a valuable alternative for treating severe/extreme obesity, despite the possible occurrence of perioperative and, more frequently, late complications, provided that it is performed by an experienced and multidisciplinary team in well-selected patients. [less ▲]Detailed reference viewed: 23 (0 ULg)
Minimal influence of the time interval between injection of regular insulin and food intake on blood glucose control of type 1 diabetic patients on a basal-bolus insulin scheme.
Scheen, André ; Letiexhe, Michel ; Lefebvre, Pierre
in Diabètes & Métabolism (1999), 25(2), 157-62
The present study aimed at investigating the influence of the time interval between injection of regular insulin and meal ingestion on postprandial glucose changes and overall blood glucose control in ... [more ▼]
The present study aimed at investigating the influence of the time interval between injection of regular insulin and meal ingestion on postprandial glucose changes and overall blood glucose control in patients with type 1 diabetes on intensive insulin therapy. Fifteen C-peptide negative subjects were submitted, in a randomized order, to two 6-week treatment periods in which regular insulin was injected either 5 minutes or 30 minutes before each of the three main meals, in combination with a bedtime NPH insulin injection. The changes in plasma glucose excursions following a breakfast test (Cmax, Tmax, Cmin, Tmin, AUC0-240 min) were similar in the two experimental protocols. Furthermore, no significant changes were observed in daily insulin dosages nor in glucose profiles obtained using home blood glucose monitoring. Only a tendency to a greater 90-minutes postprandial increase in blood glucose levels was observed when regular insulin was injected 5 minutes rather than 30 minutes before meal. Glycated haemoglobin levels were similar after each treatment period (7.6 +/- 0.2% versus 7.5 +/- 0.2%; NS) and no differences in the incidence or severity of hypoglycaemic episodes were noticed between the two insulin schemes. In conclusion, in type 1 diabetic patients who are rather well controlled with a basal-bolus insulin scheme, the injection of regular insulin 30 minutes before each main meal provides no significant advantage as compared to the injection of regular insulin 5 minutes before meal. [less ▲]Detailed reference viewed: 27 (1 ULg)
Troglitazone: antihyperglycemic activity and potential role in the treatment of type 2 diabetes.
Scheen, André ; Lefebvre, Pierre
in Diabetes Care (1999), 22(9), 1568-77
Insulin resistance is a major component of type 2 diabetes; therefore, an insulin sensitizer agent like the thiazolidinedione compound troglitazone is considered a very promising drug. Troglitazone exerts ... [more ▼]
Insulin resistance is a major component of type 2 diabetes; therefore, an insulin sensitizer agent like the thiazolidinedione compound troglitazone is considered a very promising drug. Troglitazone exerts an antihyperglycemic activity in a dose-dependent manner between 200 and 600 mg/day in type 2 diabetic patients treated with diet alone, sulfonylureas, or insulin. Additive antihyperglycemic effect may also be obtained by combining troglitazone and metformin. The antihyperglycemic effect of troglitazone as monotherapy is rather modest (reduction of HbA1c by 0.5-1.0%), but it appears to be somewhat greater when it is combined with other antidiabetic drugs. No double-blind studies have directly compared the activity of troglitazone with that of sulfonylureas or metformin. Troglitazone has been shown to exert additional beneficial effects on serum lipid profile and arterial blood pressure. It may be considered as a valuable alternative in insulin-resistant (obese and hyperinsulinemic) diabetic patients who appear to be the best responders to the drug. However, the efficacy of troglitazone is challenged by its safety profile, and the risk of hepatotoxicity still remains a major concern in clinical practice. [less ▲]Detailed reference viewed: 19 (0 ULg)