Info-congres. Les lecons de la "United Kingdom Prospective Diabetes Study".
Scheen, André ; Lefebvre, Pierre
in Revue Médicale de Liège (1998), 53(9), 576-8
The United Kingdom Prospective Diabetes Study (UKPDS) is the largest study ever performed in the field of diabetes. It has been carried on in more than 5000 patients with newly diagnosed type 2 diabetes ... [more ▼]
The United Kingdom Prospective Diabetes Study (UKPDS) is the largest study ever performed in the field of diabetes. It has been carried on in more than 5000 patients with newly diagnosed type 2 diabetes and followed during almost 15 years. The main goals of the study were to investigate the effects of improving blood glucose and/or blood pressure control on diabetic complications, and to compare the advantages and inconvenients of the most important pharmacological approaches. The results of the UKPDS have been presented at the last Congress of the European Association for the Study of Diabetes (EASD) in Barcelona, September 10-11, 1998. They essentially showed that improving blood glucose or arterial blood pressure control allows to significantly reduce the incidence of complications associated to diabetes. Best results were observed in individuals in whom treatments of both hyperglycemia and hypertension were intensified. For each risk factor, no threshold has been found so that every reduction in blood glucose or arterial pressure is accompanied by a nearly linear diminution in the incidence of diabetic complications. The type of pharmacological treatment appears to have a less prominent influence, even if metformin appears to exert the most favourable effects in the group of obese patients with type 2 diabetes. [less ▲]Detailed reference viewed: 17 (0 ULg)
Pharma clinics. Comment je traite ... un patient diabetique avec obesite severe.
Scheen, André ; ; Luyckx, Françoise et al
in Revue Médicale de Liège (1998), 53(7), 386-9
Obesity plays a crucial role in type 2 diabetes pathophysiology and a major weight loss markedly improves glycaemic control. The common failure of classical treatments leads to the use of more aggressive ... [more ▼]
Obesity plays a crucial role in type 2 diabetes pathophysiology and a major weight loss markedly improves glycaemic control. The common failure of classical treatments leads to the use of more aggressive weight-reduction approaches, such as very-low-calorie diets (VLCDs), anti-obesity drugs or even bariatric surgery. VLCDs are very successful in the short-term but rather disappointing in the long-term. Anti-obesity compounds only induce a modest mean weight reduction, even if some patients appear to be better responders. Interestingly, serotoninergic agents increase insulin sensitivity and glycaemic control, independently of weight loss. Bariatric surgery provides the most impressive results. In well-selected subjects, gastroplasty (either vertical ring gastroplasty or adjustable silicone gastric banding) generally induces a considerable weight loss which results in a remarkable and sustained glycaemic control improvement and allows the reduction, or even the suppression, of any antidiabetic treatment. This ultimate solution should not be neglected after failure of medical approaches, provided that the indication is correct, the surgical procedure is performed in a specialized centre and the followup is well organized by a multidisciplinary team. [less ▲]Detailed reference viewed: 11 (0 ULg)
Influence of the A-->G (-3826) uncoupling protein-1 gene (UCP1) variant on the dynamics of body weight before and after gastroplasty in morbidly obese subjects.
Luyckx, Françoise ; Scheen, André ; et al
in International Journal of Obesity & Related Metabolic Disorders (1998), 22(12), 1244-5Detailed reference viewed: 13 (1 ULg)
Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty.
Luyckx, Françoise ; Desaive, Claude ; Thiry, Albert et al
in International Journal of Obesity & Related Metabolic Disorders (1998), 22(3), 222-6
OBJECTIVE: To examine the factors associated with liver steatosis in severely obese subjects and to test the potential reversibility of fatty liver after weight loss. DESIGN: Retrospective clinical study ... [more ▼]
OBJECTIVE: To examine the factors associated with liver steatosis in severely obese subjects and to test the potential reversibility of fatty liver after weight loss. DESIGN: Retrospective clinical study. SUBJECT: 528 obese patients before bariatric surgery and 69 obese subjects of the initial cohort evaluated before and 27+/-15 months after gastroplasty. MEASUREMENTS: Fatty deposition (scored as mild, moderate or severe) and inflammatory changes were evaluated in liver biopsies; clinical (body mass index (BMI), age, gender, duration of obesity) and biological (glucose, triglycerides, liver enzymes) parameters were related to histological findings. RESULTS: 74% of the 528 biopsies showed fatty change, estimated as mild in 41% of cases, moderate in 32% and severe in 27%. The prevalence of steatosis was significantly higher in men than in women (91% vs 70%, P = 0.001) and in patients with impaired glucose tolerance or type 2 diabetes compared with nondiabetics (89% vs 69% P = 0.001). The severity of the steatosis was associated with BMI (P = 0.002) but not with the duration of obesity or the age of the patient. When compared with patients without fatty change, those with liver steatosis had significantly higher fasting plasma glucose (5.5 mmol/l vs 5.1 mmol/l, P = 0.007) and triglycerides (1.8 mmol/l vs 1.3 mmol/l, P = 0.002). Mean serum liver enzyme activities (alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl-transpeptidase (gammaGT) were significantly (P < 0.001) increased in patients with fatty change but remained within laboratory reference values. In the 69 patients who have been evaluated after a marked weight reduction (-32+/-19kg), 45% of the biopsies were considered as normal (vs 13% before, P < 0.001) while pure fatty change was still observed in 38% of the patients (vs 83% before, P = 0.001). However, the severity of the steatosis was significantly (P < 0.001) reduced (mild: 62% vs 21%; moderate: 23% vs 37%; severe: 15% vs 42%). In addition, a significant increase of hepatitis was observed in 26% of the biopsies (vs 14% before, P < 0.05). CONCLUSIONS: Liver steatosis in obese subjects is associated with men, diabetic status, BMI, higher fasting glucose and hypertriglyceridaemia. Postgastroplasty weight loss reduces liver steatosis, but seems to increase the incidence of inflammatory lobular hepatitis. [less ▲]Detailed reference viewed: 27 (4 ULg)
Are fasting and postload insulin good markers of cardiovascular risk factors?
Saint-Remy, Annie ; Scheen, André ; LEFEBVRE, Pierre et al
Conference (1997, December 11)Detailed reference viewed: 18 (0 ULg)
Characterization of the IGF system and analysis of the possible molecular mechanisms leading to IGF-II overexpression in a mesothelioma.
; Delacroix, Laurence ; et al
in Hormone & Metabolic Research (1997), 29(11), 549-55
The expression of members of the IGF system in a mesothelioma from a patient suffering from hypoglycemia, in term placenta and HT29 colon adenocarcinoma cells were compared. Very high levels of IGF-II ... [more ▼]
The expression of members of the IGF system in a mesothelioma from a patient suffering from hypoglycemia, in term placenta and HT29 colon adenocarcinoma cells were compared. Very high levels of IGF-II mRNA and protein were detected in the mesothelioma. Moreover, half of the IGF-II protein took the high-molecular-weight form. We also analyzed the parental imprinting status and the promoter usage of the IGF-II gene. Our results showed loss of imprinting (LOI) in the mesothelioma while the imprinting was maintained in HT29 cells, expressing moderate levels of the transcript. Promoter P4 was active in the three tissues we analyzed, whereas IGF-II mRNA transcription from promoter P3 was only detected in the mesothelioma and the placenta, expressing comparably high levels of the transcript. IGF-II gene structure was identical in the analyzed tissues and cells. The type-I receptor mRNA expression was very low in the tumor. IGFBP-2, -4 and -5 mRNAs were detected in the mesothelioma, while IGFBP-2, -3 and -5 transcripts were detected in the placenta. IGFBP-1 and -6 transcripts were not detected. [less ▲]Detailed reference viewed: 14 (0 ULg)
Acute Functional Iron Deficiency in Obese Subjects During a Very-Low-Energy All-Protein Diet
Beguin, Yves ; ; Weber, Georges et al
in American Journal of Clinical Nutrition (1997), 66(1), 75-9
We examined whether a very-low-energy all-protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients consumed for 2 wk a VLED containing 70 ... [more ▼]
We examined whether a very-low-energy all-protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients consumed for 2 wk a VLED containing 70 g protein after a 1-wk period during which total daily energy intake was progressively reduced to 1.26 MJ. Serum iron fell sharply by approximately equal to 50% (P < 0.0001), and despite a small decrease in total-iron-binding capacity, transferrin saturation decreased from 30 +/- 11% to 18 +/- 5% (P < 0.0001). Serum ferritin did not change significantly but serum soluble transferrin receptor (sTfR), an indicator of iron deficiency, increased progressively from 4630 +/- 1110 to 6070 +/- 1390 micrograms/L (P < 0.0001). Changes in sTfR correlated inversely with prior changes in serum iron. Changes in iron metabolism did not translate into changes in erythropoiesis or red cell indexes, but the white blood cell count decreased from 7.3 +/- 1.6 to 6.2 +/- 1.9 x 10(9)/L (P < 0.002). There was no evidence of deficiency for the other trace elements and minerals tested. Daily supplementation with 200 mg Fe in 18 other subjects only partially corrected these observations despite some increase in iron stores. These results indicate that during a 2-wk VLED serum iron is significantly depressed, inducing functional tissue iron deficiency too short in duration to produce alterations in red blood cell indexes. These changes are not mediated by absolute iron deficiency, inflammation, or protein malnutrition but could be related to alterations in the iron storage and release behavior of the reticuloendothelial cell during energy deprivation alone. [less ▲]Detailed reference viewed: 61 (11 ULg)
Molecular dissection of the insulin-like growth factor axis in the human thymus
Geenen, Vincent ; ; et al
in Diabetologia (1997), 40Detailed reference viewed: 11 (0 ULg)
Characterization of the insulin-like growth (IGF) axis in the human thymus
; ; Martens, Henri et al
in The Endocrine Society (Ed.) Proceedings of the 77th Annual Meeting of the Endocrine Society (1997)Detailed reference viewed: 6 (0 ULg)
Expression of insulin-related peptides in the human thymus
Geenen, Vincent ; Lefebvre, Pierre
in International Diabetes Monitor (1997), 9Detailed reference viewed: 5 (0 ULg)
Glucose turnover in humans in the basal state and after intravenous glucose: a comparison of two models.
; ; et al
in American Journal of Physiology (1997), 273(2 Pt 1), 284-96
This study investigated the ability of two models to represent glucose kinetics in the basal steady state and during an intravenous glucose tolerance test (IVGTT). Six young nonobese male subjects were ... [more ▼]
This study investigated the ability of two models to represent glucose kinetics in the basal steady state and during an intravenous glucose tolerance test (IVGTT). Six young nonobese male subjects were studied after an overnight fast. Two bolus injections of [U-13C]glucose were given 150 min apart, the first without and the second together with concomitant injection of unlabeled glucose. [3-3H]glucose was constantly infused throughout the study and served to provide an independent means for evaluation of system responses. A linear time-invariant three-compartmental model and the two-compartment time-variant model proposed by Caumo and Cobelli were used to interpret measured time courses of [U-13C]glucose and to reconstruct endogenous glucose production and glucose removal. The ability of the two models to describe the glucose tracer time course was comparable. Simulation studies showed that the two-compartmental time-variant system better predicted measured [3-3H]glucose concentration profiles than did the three-compartmental time-invariant model. However, endogenous glucose production and the integral of excess glucose removal over basal during the IVGTT derived from the two models were almost identical. [less ▲]Detailed reference viewed: 14 (0 ULg)
Reactivite bronchique chez les patients diabetiques.
Piéron, Maurice ; Scheen, André ; Corhay, Jean-Louis et al
in Revue des Maladies Respiratoires (1997), 14(5), 379-85
The data of the literature concerning bronchial reactivity in diabetic patients are controversial. Therefore, we studied the influence of the presence of a diabetic cardiac autonomic neuropathy (CAN) on ... [more ▼]
The data of the literature concerning bronchial reactivity in diabetic patients are controversial. Therefore, we studied the influence of the presence of a diabetic cardiac autonomic neuropathy (CAN) on the ventilatory parameters measured during a methacholine-induced bronchoconstriction test. Ten insulin-dependent diabetic patients without CAN, ten insulin-dependent diabetic patients with CAN and ten healthy volunteers, all non-smokers and free of respiratory symptoms, have undergone a functional respiratory check-up before the methacholine test. The presence of CAN was classically studied by the decrease in heart rate changes during three standardized tests (deep breathing at 6 cycles/min, Valsalva manoeuver, orthostatism) which all mainly explore the parasympathetic function. The bronchial response to methacholine was similar in the healthy subjects and in the diabetic patients without CAN. However, the fall in forced expiratory volume in 1 second induced by the highest dose of methacholine was significantly less marked in the diabetic subjects with CAN than in the two other groups. These results suggest that the diabetic autonomic neuropathy also involves the vagal innervation of the respiratory tract. [less ▲]Detailed reference viewed: 21 (0 ULg)
Comment j'explore ... le syndrome d'insulinoresistance grace a ses marqueurs biologiques.
Luyckx, Françoise ; Scheen, André ; Gielen, Jean-Louis et al
in Revue Médicale de Liège (1997), 52(10), 686-91Detailed reference viewed: 29 (1 ULg)
Le recepteur beta 3-adrenergique: un role dans la predisposition genetique a l'obesite et au diabete?
Luyckx, Françoise ; Scheen, André ; Gielen, Jean-Louis et al
in Revue Médicale de Liège (1997), 52(11), 703-8Detailed reference viewed: 76 (0 ULg)
Determination rapide par immunodosage de l'hemoglobine glyquee sur sang capillaire comparee a une methode d'affinite pour le boronate et capture d'ions sur sang veineux.
Bozet, Marie-Claire ; Gerard, Pascale ; Scheen, André et al
in Annales de Biologie Clinique (1997), 55(2), 139-44
Measurement of glycosylated haemoglobin has become an essential tool in the management of diabetic patients. A recently developed device allows the rapid immuno-assay of HbA1c in 1 microliter capillary ... [more ▼]
Measurement of glycosylated haemoglobin has become an essential tool in the management of diabetic patients. A recently developed device allows the rapid immuno-assay of HbA1c in 1 microliter capillary blood obtained by a finger prick. In 100 ambulatory diabetic patients, we compared the results obtained with this method to those obtained in venous blood using a standard affinity chromatography laboratory method. Although both methods correlated (r = 0.88, p < 0.001), the mean +/- SD levels respectively obtained differed slightly (7.6 +/- 1.5 vs 79 +/- 1.4% p < 0.001). The 95% confidence interval of the difference was [-0.41. -0.14]. Considering a cut-off HbA1c value of 8%, as indicative of the need for treatment adjustment, 33 patients with the capillary blood immuno-assay method and 42 with the venous-blood affinity chromatography method were above that limit (Mc Nemar test, p < 0.05). In conclusion, the rapid assay of HbA1c in capillary blood can be useful for the management of some diabetic patients but the results are not readily exchangeable with those obtained from other standardized laboratory methods. Consequently, specific ranges and clinical decision limits must be determined. [less ▲]Detailed reference viewed: 183 (0 ULg)
Plasma leptin levels, insulin secretion, clearance and action on glucose metabolism in anorexia nervosa.
Letiexhe, Michel ; Scheen, André ; Lefebvre, Pierre
in Eating and Weight Disorders [=EWD] (1997), 2(2), 79-86
From a metabolic point of view, anorexia nervosa may be viewed as a mirror image of obesity. We compared insulin secretion, clearance and action on glucose metabolism during an intravenous glucose ... [more ▼]
From a metabolic point of view, anorexia nervosa may be viewed as a mirror image of obesity. We compared insulin secretion, clearance and action on glucose metabolism during an intravenous glucose tolerance test in nine women with anorexia nervosa and in nine age-matched normal-weight controls. Insulin secretion (ISR) was derived by deconvolution of plasma C-peptide levels, insulin clearance (MCR(I)) was obtained by dividing the area under the curve (AUC(0-180 min)) of ISR by the corresponding AUC of plasma insulin levels, insulin sensitivity (S(I)) and glucose effectiveness index (S(G)) were calculated by Bergman's minimal model. The anorectic women had markedly lower BMI values (13.7+/-0.6 vs 23.2+/-0.8 kg/m2, p<0.0001) and serum basal leptin levels (2.8+/-0.6 vs 8.9+/-1.8 ng/mL, p=0.005) than control women. The anorectic women exhibited clear-cut lower fasting and post-glucose plasma insulin levels but similar corresponding plasma C-peptide concentrations when compared to controls. Consequently, ISR was similar in both groups while MCR(I) was significantly increased in anorexia nervosa (MCR(I): 3320+/-881 vs 822+/-79 mL x min(-1) x m(-2), p<0.02). The index S(I) tended to be higher in anorectic women than in normal-weight subjects, but without reaching the level of statistical significance because of a high between-subject variability (20.2+/-5.7 vs 12.5+/-2.2 10(-5) x min(-1)/pmol x L(-1), NS). The index S(G) was similar in both groups (0.022+/-0.004 vs 0.018+/-0.002 min(-1), NS). In conclusion, low plasma insulin levels observed in women with anorexia nervosa result from high MCR(I) rather than from depressed insulin secretion. Insulin sensitivity is not systematically increased and glucose effectiveness is unchanged in anorectic women when compared to normal-weight controls. [less ▲]Detailed reference viewed: 46 (0 ULg)
Thymic insulin-like growth factors (IGFs) in man and in an animal model of autoimmune IDDM
Geenen, Vincent ; ; et al
in Diabetologia (1996), 39Detailed reference viewed: 6 (0 ULg)
Exhaustion of blood glucose response and enhancement of insulin response after repeated glucagon injections in type-2 diabetes: potentiation by progressive hyperglycemia.
; Scheen, André ; et al
in Annales d'Endocrinologie (1996), 57(5), 395-402
AIMS: To investigate the hyperglycemic and insulinemic response to repeated glucagon injections in Type-2 (non-insulin-dependent) diabetic patients. METHODS: In overnight fasted Type-2 diabetic patients ... [more ▼]
AIMS: To investigate the hyperglycemic and insulinemic response to repeated glucagon injections in Type-2 (non-insulin-dependent) diabetic patients. METHODS: In overnight fasted Type-2 diabetic patients, three i.v. glucagon (1 mg) injections were given as a bolus at two-hour intervals. In the hour preceding each glucagon injection, 6 patients received saline and they were tested at near-baseline blood glucose levels, while 8 patients received a glucose-controlled glucose infusion and they were tested at increasing blood glucose levels (7.5 +/- 0.2, 12.9 +/- 0.5 and 18.7 +/- 0.7 mmol/l). Blood samples were collected at 0, 3, 5, 10, 15, 30 and 60 min after each glucagon injection. RESULTS: In the patients tested at near-baseline blood glucose levels, the blood glucose rise induced by glucagon was smaller after repeated injections. By contrast, the B-cell response to glucagon was well preserved. In the patients tested at increasing blood glucose levels, the blood glucose response to glucagon was abolished after repeated injections. By contrast, the B-cell response was significantly potentiated. The respective areas under the curve of plasma insulin levels in response to glucagon were 563 +/- 72, 1047 +/- 154 and 1844 +/- 305 m U x 30 min/l (p < 0.001). CONCLUSION: In Type-2 (non-insulin-dependent) diabetic patients, repeated glucagon injections, even when administered in a short (4 h) period of time, do not exhaust the B-cell. Endogenous insulin secretion is even potentiated at increasing blood glucose levels. By contrast, the hyperglycemic response to glucagon is significantly abolished, particularly at high blood glucose levels. [less ▲]Detailed reference viewed: 12 (0 ULg)
The degree/rapidity of the metabolic deterioration following interruption of a continuous subcutaneous insulin infusion is influenced by the prevailing blood glucose Level.
; Scheen, André ; Lefebvre, Pierre
in Journal of Clinical Endocrinology and Metabolism (1996), 81(5), 1975-8
This study aims at investigating the influence of the prevailing blood glucose level on the metabolic deterioration that follows a nocturnal interruption of a continuous sc insulin infusion (CSII ... [more ▼]
This study aims at investigating the influence of the prevailing blood glucose level on the metabolic deterioration that follows a nocturnal interruption of a continuous sc insulin infusion (CSII). Fifteen CSII-treated, C-peptide negative, diabetic patients have been studied CSII was interrupted from 2300 h to 0500 h. Blood was collected hourly from 2200 h to 0600 h. According to blood glucose (BG) levels at 2300 h, patients were classified as hypoglycemic (BG between 1.5 and 2.5 mmol/L, n = 5), normoglycemic (BG between 4.0 and 8.0 mmol/L, n = 5), or hyperglycemic (BG between 9.0 and 15.0 mmol/L, n = 5). At 2300 h, BG (mean +/- SEM) was 1.9 +/- 0.1, 6.2 +/- 0.7 and 11.2 +/- 1.0 mmol/L, respectively. After 6 h of CSII interruption, BG increased to 13.5 +/- 1.3, 14.1 +/- 1.2, and 19.4 +/- 1.2 mmol/L, respectively. At 2300 h, plasma 3-OH-butyrate levels were similar in the three groups (around 150 micromol/L). At 0500 h, significantly higher values were obtained for hyperglycemic (1460 +/- 127 micromol/L) than for normoglycemic (868 +/- 150 micromol/L) or hypoglycemic (837 +/- 80 micromol/L) patients. Enhanced lipolysis in initially hyperglycemic patients may contribute to accelerated ketogenesis and metabolic degradation. In conclusion, the metabolic deterioration that follows CSII interruption is influenced by the initial metabolic situation. Hypoglycemic patients deteriorate more rapidly, and hyperglycemic patients suffer a more important degradation. The latter are prone to rapid ketoacidosis if accidental CSII interruption occurs. [less ▲]Detailed reference viewed: 9 (1 ULg)