Philippe Boudou

Exercise training-induced triglyceride lowering negatively correlates with DHEA levels in men with type 2 diabetes

OBJECTIVE: To investigate the effect of an exercise training program on lipid profile in correlation with DHEA level and body weight and body composition in type 2 diabetic men.DESIGN: Longitudinal, controlled clinical intervention study with exercise training consisting of an 8 week supervised program of aerobic exercise (75% VO2 peak, 45u2005min), twice a week and intermittent exercise, once a week, on a bicyle ergometer.SUBJECTS: Sixteen men (age 45.4±7.2u2005y (mean±s.d.), HbA1c 8.15±1.7%, body mass index (BMI) 29.6±4.6u2005kg/m2) were randomly divided into two groups: trained group (n=8) and control group (n=8).MEASUREMENTS: Lipid, apo- and lipoprotein and DHEA concentrations. Cross-sectional areas of subcutaneous and visceral adipose tissue and mid-thigh muscle by magnetic resonance imaging.RESULTS: Training decreased visceral (153.25±38.55 vs 84.20±21.30u2005cm2, P<0.001), subcutaneous (241.55±49.55 vs 198.00±39.99u2005cm2, P<0.001) adipose tissue area and triglyceride levels (2.59±1.90 vs 1.79±1.08u2005nmol/l, P<0.05) and increased mid-thigh muscle cross-sectional area (148.30±36.10 vs 184.35±35.85u2005cm2, P<0.001), and DHEA levels (11.00±3.10 vs 14.25±4.10u2005nmol/l, P<0.05) with no modification in body weight. Changes in triglycerides were negatively correlated with changes in DHEA (r=−0.81, P=0.03). This correlation was independent of changes in abdominal fat distribution.CONCLUSION: Training decreases abdominal fat depots, improves muscular mass and affects favourably triglyceride and DHEA levels. Changes in triglycerides and DHEA were inversely related.

Multitissue Insulin Resistance Despite Near-Normoglycemic Remission in Africans With Ketosis-Prone Diabetes

OBJECTIVE—To characterize insulin action in Africans with ketosis-prone diabetes (KPD) during remission. RESEARCH DESIGN AND METHODS—At Saint-Louis Hospital, Paris, France, 15 African patients with KPD with an average 10.5-month insulin-free near-normoglycemic remission period (mean A1C 6.2%) were compared with 17 control subjects matched for age, sex, BMI, and geographical origin. Insulin stimulation of glucose disposal, and insulin suppression of endogenous glucose production (EGP) and nonesterified fatty acids (NEFAs), was studied using a 200-min two-step (10 mU · m−2 body surface · min−1 and 80 mU · m−2 · min −1 insulin infusion rates) euglycemic clamp with [6,6-2H2]glucose as the tracer. Early-phase insulin secretion was determined during an oral glucose tolerance test. RESULTS—The total glucose disposal was reduced in patients compared with control subjects (7.5 ± 0.8 [mean ± SE] vs. 10.5 ± 0.9 mg · kg−1 · min−1; P = 0.018). EGP rate was higher in patients than control subjects at baseline (4.0 ± 0.3 vs. 3.0 ± 0.1 mg · kg−1 · min−1; P = 0.001) and after 200-min insulin infusion (10 mU · m−2 · min−1: 1.6 ± 0.2 vs. 0.6 ± 0.1, P = 0.004; 80 mU · m−2 · min−1: 0.3 ± 0.1 vs. 0 mg · kg−1 · min−1, P = 0.007). Basal plasma NEFA concentrations were also higher in patients (1,936.7 ± 161.4 vs. 1,230.0 ± 174.1 μmol/l; P = 0.002) and remained higher after 100-min 10 mU · m−2 · min−1 insulin infusion (706.6 ± 96.5 vs. 381.6 ± 55.9 μmol/l; P = 0.015). CONCLUSIONS—The triad hepatic, adipose tissue, and skeletal muscle insulin resistance is observed in patients with KPD during near-normoglycemic remission, suggesting that KPD is a form of type 2 diabetes.

Establishment and Characterization of a Human Adrenocortical Carcinoma Xenograft Model

Adrenocortical carcinomas are rare malignant tumors. They have a poor prognosis, as they are often diagnosed late and are usually resistant to chemotherapy. The lack of a suitable animal model for these tumors has been a major obstacle to the evaluation of new therapeutic agents. The aim of this study was to establish and characterize xenografts of the human adrenocortical carcinoma NCI H295R cell line as a model of adrenocortical carcinoma for future therapeutic trials. This cell line was sc injected (6 3 10 6 cells) into nude mice (n 5 20). Solid tumors were locally measurable after 45 days at 90% of the inoculation sites. The xenografts were similar histologically to the original adrenocortical carcinoma from which the cell line was derived. The xenografts precisely reproduced the dysregulation of the insulin-like growth factor (IGF) system [overexpression of the IGF-II and IGF-binding protein-2 (IGFBP-2) genes] typical of adrenocortical carcinoma. Similarly to adrenocortical carcinomas, human IGFBP-2 (but not IGF-II) was secreted in mouse plasma. We analyzed steroid production (cortisol, 17-hydroxypregnenolone, 17hydroxyprogesterone, dehydroepiandrosterone, D 4 -androstenedione, 11-deoxycortisol, corticosterone, and testosterone). Xenografts produced all three class of steroids, with the preferential production of androgens of the D 4 pathway. The H295R xenograft model is a good model of human adrenocortical carcinoma, as it mimics dysregulation of the IGF system usually found in these tumors. It also produces IGFBP-2 and steroids that can be used as tumor markers. This model may therefore be useful for evaluating therapeutic agents. (Endocrinology 141: 3165‐3171, 2000)

One-year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes

Recombinant methionyl human leptin (metreleptin) therapy was shown to improve hyperglycaemia, dyslipidaemia and insulin sensitivity in patients with lipodystrophic syndromes, but its effects on insulin secretion remain controversial. We used dynamic intravenous (i.v.) clamp procedures to measure insulin secretion, adjusted to insulin sensitivity, at baseline and after 1u2009year of metreleptin therapy, in 16 consecutive patients with lipodystrophy, diabetes and leptin deficiency. Patients, with a mean [± standard error of the mean (s.e.m.)] age of 39.2 (±4)u2009years, presented with familial partial lipodystrophy (nu2009=u200911, 10 women) or congenital generalized lipodystrophy (nu2009=u20095, four women). Their mean (± s.e.m.) BMI (23.9u2009±u20090.7u2009kg/m2), glycated haemoglobin levels (8.5u2009±u20090.4%) and serum triglycerides levels (4.6u2009±u20090.9u2009mmol/l) significantly decreased within 1 month of metreleptin therapy, then remained stable. Insulin sensitivity (from hyperglycaemic or euglycaemic‐hyperinsulinaemic clamps, nu2009=u20094 and nu2009=u200912, respectively), insulin secretion during graded glucose infusion (nu2009=u200912), and acute insulin response to i.v. glucose adjusted to insulin sensitivity (disposition index, nu2009=u200912), significantly increased after 1u2009year of metreleptin therapy. The increase in disposition index was related to a decrease in percentage of total and trunk body fat. Metreleptin therapy improves not only insulin sensitivity, but also insulin secretion in patients with diabetes attributable to genetic lipodystrophies.

Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population

BackgroundThere is little data on the metabolic effects of adipokines in sub-Saharan African populations. This study aimed to explore the potential relationship of leptin and adiponectin, with obesity, plasma lipids and insulin resistance in a Cameroonian population.MethodsWe enrolled 167 men and 309 women aged ≥18xa0years from the general population in Cameroon. Data were collected on waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), body fat (BF%), fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). Pearson’s correlation and multiple stepwise linear regression analyses were used to determine correlates of leptin and adiponectin serum levels.ResultsThe prevalence of obesity was higher in women compared to men (pu2009<u20090.0001), and Central obesity which is more prevalent particularly in women (WCu2009=u200942.4xa0%, WHRu2009=u200942.3xa0%), is almost for 90xa0% comparable to %BF (42.7xa0%).Adiponectin negatively with BMI (ru2009=u2009−0.294, pu2009<u20090.0001), WC (ru2009=u2009−0.294, pu2009<u20090.0001), %BF (ru2009=u2009−0.122, pu2009=u20090.028), WHR (ru2009=u2009−0.143, pu2009=u20090.009), triglycerides (ru2009=u2009−0.141, pu2009=u20090.011), HOMA-IR (ru2009=u2009−0.145, pu2009=u20090.027) and insulin (ru2009=u2009−0.130, pu2009=u20090.048). Leptin positively correlated with BMI (ru2009=u20090.628), WC (ru2009=u20090.530), BF% (ru2009=u20090.720), (all pu2009<u20090.0001); with DBP (ru2009=u20090.112, pu2009=u20090.043), total cholesterol (ru2009=u20090.324, pu2009<u20090.0001), LDL-cholesterol (ru2009=u20090.298, pu2009<u20090.0001), insulin (ru2009=u20090.320, pu2009<u20090.001 and HOMA-IR (ru2009=u20090.272, pu2009<u20090.0001).In multiple stepwise regression analysis, adiponectin was negatively associated with WC (βu2009=u2009−0.38, pu2009=u20090.001) and BF% (βu2009=u20090.33, pu2009<u20090.0001), while leptin was positively associated with BF% (βu2009=u20090.60, pu2009<u20090.0001), total cholesterol (βu2009=u20090.11, pu2009=u20090.02) and HOMA-IR (βu2009=u20090.11, pu2009=u20090.02). When controlled for gender, HOMA-IR was found significantly associated to adiponectin (βu2009=u20090.13, pu2009=u20090.046), but not BF%, while the association previously found between leptin and HOMA-IR disappeared; BMI and WC were significantly associated with leptin (βu2009=u20090.18, pu2009=u20090.04 & βu2009=u20090.19, pu2009=u20090.02 respectively).ConclusionThis study, which includes a population who was not receiving potentially confounding medications, confirms the associations previously observed of adiponectin with reduced adiposity especially central adiposity and improved insulin sensitivity. Confirmatory associations were also observed between leptin and obesity, blood lipids and insulin resistance for the first time in an African population. Gender was significant covariate interacting with insulin sensitivity/insulin resistance and obesity indexes associations in this population.

Osteoprotegerin in relation to insulin resistance and blood lipids in sub-Saharan African women with and without abdominal obesity

BackgroundOsteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily that inhibits bone resorption, has been suggested as a potential marker of cardiovascular risk. This study aimed to assess the relationship between insulin resistance, lipid profile and OPG levels in obese and non-obese sub-Saharan African women.MethodsSixty obese (44) and non-obese (16) volunteer women aged 18 to 40xa0years were recruited in this cross-sectional study. Their clinical (age, height, weight, waist circumference, systolic and diastolic blood pressures) and biochemical parameters (fasting blood glucose, total cholesterol, high density lipoprotein-cholesterol (HDL-C)) were measured using standard methods. Insulin levels were measured using an electrochemiluminescence immunoassay, while OPG levels were measured using the ELISA technique. Low density lipoprotein-cholesterol (LDL-C), body mass index (BMI) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) were calculated using standard methods. Abdominal obesity was defined as a waist circumferenceu2009≥u200980xa0cm.ResultsOPG levels were higher in obese than in normal subjects, though the difference was not significant (pu2009=u20090.9). BMI, waist circumference, percent body fat and systolic blood pressure were significantly higher in obese than in non-obese subjects (pu2009<u20090.05). In these subjects, only age significantly correlated with OPG levels (ru2009=u20090.831, pu2009=u20090.003), while none of the anthropometric nor metabolic parameter did, even after adjustment for age. In obese subjects, OPG levels fairly correlated with HDL-C (ru2009=u20090.298, pu2009=u20090.058), and significantly correlated with HOMA-IR (ru2009=u2009−0.438, pu2009=u20090.018). After adjustment for age, OPG levels remained negatively correlated to HOMA-IR (ru2009=u2009−0.516, pu2009=u20090.020) and LDL-C (ru2009=u2009−0.535, pu2009=u20090.015) and positively correlated to HDL-C (ru2009=u20090.615, pu2009=u20090.004). In multiple linear regression analysis, age was a main determinant of OPG levels in non-obese (βu2009=u20090.647, pu2009=u20090.006) and obese (βu2009=u20090.356, pu2009=u20090.044) women. HDL-C was also associated to OPG levels in obese women (βu2009=u20090.535, pu2009=u20090.009).ConclusionThe positive correlation of OPG with HDL-C and HOMA-IR, and its negative correlation with LDL-C suggest that it may be a marker of insulin sensitivity/resistance and atherogenic risk in obese African women.

Association of the leptin-to-adiponectin ratio with metabolic syndrome in a sub-Saharan African population

BackgroundWorldwide there is an increased prevalence of metabolic syndrome mainly due to life-style modifications, and Africans are not saved of this situation. Many markers have been studied to predict the risk of this syndrome but the most used are leptin and adiponectin. Data on these metabolic markers are scare in Africa and this study aimed to assess the association between the leptin-to-adiponectin ratio (LAR) with metabolic syndrome in a Cameroonian population.MethodsThis was a cross-sectional study that included 476 adults among a general population of Cameroon. Data collected concerned the body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). To assess correlations we used Spearman’s analyses and association of the studied variables with metabolic syndrome were done using binary logistic regression analysis.ResultsThe leptin to adiponectin ratio was significantly and positively correlated with the body mass index (rxa0=xa00.669, pxa0<xa00.0001), waist circumference (rxa0=xa00.595, pxa0<xa00.0001), triglycerides (rxa0=xa00.190, pxa0=xa00.001), insulin levels (rxa0=xa00.333, pxa0<xa00.0001) and HOMA-IR (rxa0=xa00.306, pxa0<xa00.0001). Binary logistic regression analysis revealed that leptin, adiponectin and LAR were significantly associated with metabolic syndrome with respective unadjusted OR of 1.429, 0.468 and 1.502. After adjustment, for age and sex, the associations remained significative; LAR was also found to be significantly associated with metabolic syndrome (ORxa0=xa01.573, p value =0.000) as well as lower levels of adiponectin (ORxa0=xa00.359, p value =0.000) and higher levels of leptin (ORxa0=xa01.469, p value =0.001).ConclusionThis study revealed that LAR is significantly associated with metabolic syndrome in sub-Saharan African population, independently to age and sex.

SEIN7 Optimisation des prelevements en senologie

Objectifs Presenter les nouvelles techniques d’analyse utilisees par le pathologiste en senologie. Optimiser la technique de prelevement en fonction de la pathologie. Rappeler les techniques de conditionnement des prelevements (fixation, congelation…) en fonction de la pathologie recherchee. Materiels et methodes En radiologie, les options de prelevements prennent en compte : le systeme de biopsie (cytoponction, microbiopsie ou macrobiopsie avec aspiration), la methode de guidage (echographique, stereotaxie et IRM) et le conditionnement (AFA, congelation, etalement sur lame). En pathologie, l’analyse inclut notamment l’etude cytologique, histologique, l′immunohistochimie (recepteurs hormonaux et HER2…) et la biologie moleculaire. Les prelevements peuvent egalement etre conserves en tumorotheque. Resultats Les questions posees au pathologiste varient en fonction de la nature probable de la lesion. Si une chimiotherapie neoadjuvante est envisagee, l’analyse anatomopathologique des tumeurs doit etre realisee avant la mise en route du traitement. Elle constituera l’unique examen de reference, ces traitements en modifiant l’aspect histologique. La confirmation histologique de la nature adenofibromateuse d’une lesion ne necessite qu’une analyse plus sommaire. Conclusion Le radiologue doit adapter ses techniques de prelevements a la nature probable de la lesion afin d’optimiser l’etude anatomopathologique avant traitement.

Optimisation des prelevements en senologie

Objectifs Presenter les nouvelles techniques d’analyse utilisees par le pathologiste en senologie. Optimiser la technique de prelevement en fonction de la pathologie. Rappeler les techniques de conditionnement des prelevements (fixation, congelation …) en fonction de la pathologie recherchee. Materiels et methodes En radiologie, les options de prelevements prennent en compte : le systeme de biopsie (cytoponction, microbiopsie ou macrobiopsie avec aspiration), la methode de guidage (echo-graphique, stereotaxie et IRM) et le conditionnement (AFA, congelation, etalement sur lame). En pathologie, l’analyse inclut notamment l’etude cytologique, histologique, l’immunohistochimie (recepteurs hormonaux et HER2 …) et la biologie moleculaire. Les prelevements peuvent egalement etre conserves en tumorotheque. Resultats Les questions posees au pathologiste varient en fonction de la nature probable de la lesion. Si une chimiotherapie neoadjuvante est envisagee, l’analyse anatomo-pathologique des tumeurs doit etre realisee avant la mise en route du traitement. Elle constituera l’unique examen de reference, ces traitements en modifiant l’aspect histologiue. La confirmation histologique de la nature adenofibromateuse d’une lesion ne necessite qu’une analyse plus sommaire. Conclusion Le radiologue doit adapter ses techniques de prelevements a la nature probable de la lesion afin d’optimiser l’etude anatomo-pathologique avant traitement.