Françoise Luyckx

Liver abnormalities in severely obese subjects: Effect of drastic weight loss after gastroplasty

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 (γGT) 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±19 kg), 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.

NONALCOHOLIC STEATOHEPATITIS AND INSULIN RESISTANCE : INTERFACE BETWEEN GASTROENTEROLOGISTS AND ENDOCRINOLOGISTS

Abstract Nonalcoholic steatohepatitis (NASH), along with other forms of nonalcoholic fatty liver disease, is an increasingly common clinico-pathological syndrome. It is frequently associated with obesity, especially visceral fat, and type 2 diabetes, and is intimately related to markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance. The pathophysiology of NASH involves two steps : 1) insulin resistance, which causes steatosis; 2) and oxidative stress, which produces lipid peroxidation and activates inflammatory cytokines. The identification of subjects who may progress from fatty liver to NASH, and from NASH to fibrosis/cirrhosis is an important clinical challenge as well as the finding of appropriate therapy that could prevent such deleterious process. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by an important regression of liver steatosis in most patients, although mild inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome and perhaps being part of it.

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.

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

Severe/extreme obesity: a medical disease requiring a surgical treatment?

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.

L'hyperglycemie provoquee par voie orale. Etude de la secretion, de la clairance et de l'action de l'insuline, et du retrocontrole par les hormones de la contre-regulation

Resume L’hyperglycemie provoquee par voie orale (HGPO) a ete tres utilisee pour diagnostiquer un diabete sucre, un diabete gestationnel, une diminution de la tolerance au glucose, voire une hypoglycemie reactionnelle. Les mesures concomitantes de l’insulinemie (eventuellement du peptide-C) et de la glycemie permettent de deriver des indices d’insulinosecretion et d’insulinosensibilite tres utiles pour mieux comprendre les perturbations du metabolisme du glucose et, en particulier, suivre l’histoire naturelle d’un diabete de type 2. La clairance de l’insuline peut etre approchee par une etude du rapport molaire peptide-C/insuline, mais il est preferable d’etudier ce parametre en etat d’equilibre plutot que lors d’un test dynamique comme l’HGPO. Enfin, la determination simultanee des hormones de la contre-regulation permet de mettre en evidence des anomalies de reponse en hormone de croissance pouvant contribuer au diagnostic et au suivi de l’acromegalie. Ainsi, l’HGPO garde des potentialites importantes pour la recherche dans le domaine du metabolisme et de l’endocrinologie.

Persistent low levels of serum hCG due to heterophilic mouse antibodies: an unrecognized pitfall in the diagnosis of trophoblastic disease.

Abstract Phantom hCG refers to persistent mild elevations of hCG, leading physicians to unnecessary treatments whereas neither a true hCG nor a trophoblastic disease is present. We report the case of a 23-year-old woman with persistent low levels of serum hCG detected one month after miscarriage. As choriocarcinoma was suspected, a chemotherapy trial of methotrexate was prescribed, without any hCG reduction. Subsequently, laparoscopy ruled out a trophoblastic residue and the patient was referred to the Endocrine Unit for further investigations. While low levels of hCG were still detected in serum, no hCG was detected in the urine. In addition, when serum was processed in a HBT tube for revealing heterophilic antibodies, hCG was no longer detected. Such finding indicated the presence of phantom hCG due to heterophilic mouse antibodies interaction. This case raises the need of clinico-biological discussion to avoid inappropriate therapeutic decisions. Based on this case experience and after review of the literature, we suggest that current gynecological protocols for the diagnosis and treatment of trophoblastic disease should consider the inclusion of urinary hCG and/or a test for serum heterophilic antibodies when appropriate.

L’hyperglycémie provoquée par voie orale (HGPO) revisitée 1re partie : Tolérance au glucose, diabète gestationnel et hypoglycémie réactive

L’hyperglycemie provoquee par voie orale (HGPO) a ete tres utilisee pour diagnostiquer un diabete sucre, un diabete gestationnel, une diminution de la tolerance au glucose, voire une hypoglycemie reactionnelle. Cependant, depuis une dizaine d’annees, certains ont propose de limiter l’utilisation de ce test dynamique au profit de la mesure soit de la glycemie a jeun, soit de l’hemoglobine glyquee. Neanmoins, pratiquement toutes les grandes etudes recentes font reference a l’HGPO comme test de reference. Dans ce premier article, nous focaliserons notre attention sur l’interet potentiel de l’HGPO comme epreuve diagnostique et pronostique capable d’evaluer la regulation glycemique. Dans un second article, nous decrirons comment utiliser l’HGPO pour deriver des indices evaluant quantitativement l’insulinosecretion et/ou l’insulinosensibilite.

Analysis of the discriminant ability of shorter versions of the French ADAM questionnaire

Objective. To investigate whether shorter versions of the ADAM test, a screening questionnaire for andropause, provide better diagnostic value than the original tool. Methods. Five thousand and twenty-eight volunteer men aged 50–70 years attending a screening campaign for andropause, provided a fasting blood sample and completed the French ADAM test. Logistic regression analysis identified items that best predict andropause defined as serum free testosterone level below 70 ng/l. ROC curves assessed the diagnostic value of modified versions of the ADAM test, obtained by elimination of the less relevant predictors of andropause. Results. Only four items of the ADAM questionnaire may account for the diagnosis of andropause. These items concerned loss of height, decrease in libido and in enjoyment of life and deterioration in work performance. Item 9 was borderline significant. The area under the ROC curve for the short versions varied slightly from 0.555 to 0.560. As expected, model 6 has a greater specificity (56.02%) than the original tool while the efficiency increased slightly (54.85%). Conclusion. The modified versions of the ADAM test do not provide better diagnostic value than the original tool.