CONTEXT:Cystic fibrosis-related diabetes is primarily due to a defect in insulin secretion. Women with cystic fibrosis (CF) are at higher risk of developing CF-related diabetes.OBJECTIVE:The objective of the study was to examine sex differences in insulin and glucose homeostasis. We hypothesized that in CF, women would display lower insulin secretion than men.DESIGN:This was a study based on an ongoing observational CF cohort with a mean follow-up of 19.9 ± 5.2 months.SETTING:The study was conducted at the CF clinic of the Centre Hospitalier de l'Université de Montréal (Québec, Canada).PATIENTS:From 230 adults with CF (123 men, 107 women) of similar age and functional pulmonary status, 104 retested after the follow-up. Age-matched healthy individuals (25 men, 19 women) were included in the study.INTERVENTIONS:Participants underwent a 2-hour oral glucose tolerance test with 30-minute interval sample measurements.MAIN OUTCOME MEASURE:Plasma insulin and glucose levels were measured.RESULTS:Women with CF had higher overall insulin secretion as compared with men with CF (P ≤ .05) but similar to healthy women (P = .606). Men with CF had lower overall insulin secretion than healthy men (P = .020) and higher insulin sensitivity (P = .009) than women with CF. PATIENTS with CF displayed higher overall glucose excursions than healthy patients. Sex-related differences were still observed in the CF cohort after follow-up.CONCLUSIONS:Surprisingly, in CF, adult women presented higher insulin secretion than adult men at a comparable level with what is observed in healthy individuals. Potential implications of this sex dimorphism in CF remain to be established.

BackgroundRecent studies have identified hypertriglyceridemic cystic fibrosis patients (CF-TG). However, whether hypertriglyceridemia is associated with an altered metabolic profile remains unknown.ObjectiveTo characterize CF-TG and determine whether triglycerides (TG) levels are associated with metabolic alterations.Methods210 adult CF subjects from the Montreal Cystic Fibrosis Cohort without known diabetes were included in the analysis. All subjects underwent an OGTT to assess glucose tolerance, insulin secretion (insulin AUC) and insulin sensitivity (Stumvoll index). Fasting lipid profiles, pulmonary function (%FEV1) and BMI were determined. Hypertriglyceridemia (TG>1.7mmol/L) was observed in 20 CF patients. These subjects were matched for age, sex and glucose tolerance category with 20 CF patients (CF-normal-TG) and 20 healthy controls that had TG levels below 1.7mmol/L. Pearson correlations were performed in the complete study sample (n=210) to examine the associations between TG levels and other parameters.ResultsThe prevalence of hypertriglyceridemia was 9.5%. Compared to CF-normal-TG, CF-TG subjects displayed significantly higher %FEV1, insulin AUC (AUC0–120, AUC0–30, AUC30–120), cholesterol levels and a higher ratio of total cholesterol to HDL-cholesterol. Pearson analysis demonstrated that TG levels were associated with BMI, %FEV1, fasting insulin, insulin AUC0–120 and AUC30–120, Stumvoll index, cholesterol levels and the ratio of total cholesterol to HDL-cholesterol. All these correlations remained significant after correction for BMI except %FEV1.ConclusionTG levels are associated with a mild alteration of the metabolic profile. Whether these changes will increase the long-term risk of CF patients in developing cardiometabolic complications remains to be investigated.

BACKGROUND:The median life expectancy of cystic fibrosis (CF) patients has increased dramatically over the last few years and we now observe a subset of patients with a body mass index (BMI) exceeding 25 kg/m(2). The aim of this study was to characterize these individuals and to identify factors associated with higher BMI.METHODS:This is a cross sectional study including 187 adult CF subjects. Percent predicted forced expiratory volume in 1s (%FEV(1)), blood lipid profiles as well as fasting glucose and insulin levels were evaluated. Subjects also had an oral glucose tolerance test (OGTT) and the area under the curve (AUC) for glucose and insulin was calculated. CF subjects were then stratified according to the following BMI categories: underweight: BMI≤18.5 kg/m(2); normal weight: 18.5 kg/m(2)<BMI<25 kg/m(2); and overweight or obese: BMI≥25 kg/m(2).RESULTS:Overweight subjects were older and less likely to have enzyme supplementation compared to the other two groups. Furthermore, this group exhibits higher levels of fasting insulin, total and LDL-cholesterol as well as insulin AUC. Further analyses demonstrated that BMI correlated with %FEV(1), fasting insulin, insulin AUC, total cholesterol, LDL-cholesterol and the ratio of HDL-cholesterol to total cholesterol and that %FEV(1), insulin AUC and LDL-cholesterol were independent associated with BMI.DISCUSSION:Overweight CF subjects have higher fasting insulin and insulin AUC as well as total and LDL-cholesterol. Furthermore, we also demonstrated that LDL-cholesterol, insulin AUC are independently associated with BMI in a population of adult CF subjects.

Introduction: Cystic fibrosis (CF) is the most common lethal autosomal recessive disease among Caucasians, affecting one in 3600 births in Canada. CF is known as a disease of thinness due to malabsorption and malnutrition, and respiratory failure is the principal cause of CF mortality. The main objectives were to assess CF body composition and to investigate its association with pulmonary function.

Cystic fibrosis (CF)-related diabetes is an important complication of CF caused by a decrease in insulin secretion that is associated with weight loss, poor nutritional status and increased mortality. Leptin, a hormone secreted from white adipose tissue, has an important role in energy homoeostasis by inhibiting food intake and increasing energy expenditure. Leptin secretion can be increased by nutrient signals such as insulin.Aims. - Considering that leptin plays a role in energy homoeostasis and that CF is associated to poor weight gain and decreased insulin secretion, leptin levels in CF patients with different glucose tolerances were investigated and compared with those of healthy control subjects.Methods. Two-hour oral glucose tolerance tests (OGTT) were performed in 82 patients with CF and various glucose tolerances as well as in 17 healthy control subjects during which blood was withdrawn every 30 min to measure glucose and insulin. Fasting leptin, fibrinogen and fat mass were also measured, and body mass index (kg/m(2)) calculated for all participants. Early and late insulin secretion was separated by calculating the area under the curve from time 0 to 30 min and 30 to 120 min of the OGTT (AUC(0-30) and AUC(30-120)).Results. - Leptin levels were comparable between CF patients and healthy control subjects. Interestingly, correlations were observed between leptin levels and insulin (AUC(0-120) and AUC(30-120)) after adjusting for gender and fat mass (P < 0.05).Conclusion. - This study suggests a potential role of insulin in regulating leptin levels in adults with stable CF. (C) 2011 Elsevier Masson SAS. All rights reserved.

286 Dyslipidemia in the Montreal cystic fibrosis cohort L. Belson1,2,3, S. Ziai1,2,3, L. Coderre1,4, Y. Berthiaume4,5, R. Rabasa-Lhoret1,3,4. 1Institut de Recherches Cliniques de Montreal, Montreal, Canada; 2University of Montreal, Nutrition, Montreal, Canada; 3Montreal Diabetes Research Center, Montreal, Canada; 4University of Montreal, Medicine, Montreal, Canada; 5Cystic Fibrosis Clinic, Montreal, Canada

Introduction Contrairement a la population generale, les personnes atteintes de mucoviscidose (MV) ont, depuis leur plus jeune âge, pour principale recommandation nutritionnelle une diete riche en gras et en calories. Ceci est principalement du au fait que, malgre la prise importante d’enzymes pancreatiques (pres de 80 %), une malabsorption intestinale persiste. Les principaux objectifs de cette etude sont de caracteriser les profils lipidiques, d’analyser les causes et les complications eventuelles de ces anomalies chez des patients MV ainsi que mettre en evidence une eventuelle association avec les anomalies de la tolerance au glucose. Patients et methodes 204 sujets MV et 15 sujets non-MV ont ete inclus dans cette etude. Tous les sujets ont subi une hyperglycemie provoquee oralement (HGPO) afin de determiner leur tolerance au glucose. Les profils lipidiques incluant entre autres cholesterol total, HDL, LDL et triglycerides ont ete mesures a jeun. Une balance electronique a ete utilisee pour determiner la masse grasse, la masse maigre ainsi que l’indice de masse corporelle (IMC). Une hypertriglyceridemie (HPTG) a ete retrouvee chez 20 patients MV qui ont par la suite ete apparies avec 20 patients MV non-HPTG. Les criteres d’appariement etaient : sexe, âge, insuffisance pancreatique, genotype et statut de tolerance au glucose. Resultats La comparaison des trois groupes (MV-HPTG, MV-non HPTG et non-MV) a mis en evidence des differences sur la secretion et la resistance a l’insuline. Pour un statut glycemique comparable, les patients MV-HPTG avaient une sensibilite a l’insuline moindre entrainant une plus forte secretion d’insuline. L’IMC, la tension arterielle, l’inflammation et la capacite pulmonaire ne semblent pas differer entre les groupes MV-HPTG et MV-non HPTG. Les femmes ont une tendance a etre plus souvent atteintes d’HPTG que les hommes. Discussion L’HPTG chez les patients MV semble etre un phenomene isole et ne semble pas avoir les complications rencontrees dans la population generale.

Recently, our group published a paper in the Journal validating, in cystic fibrosis (CF) patients, surrogate insulin secretion indices against the gold standard method, the Intravenous Glucose Tolerance Test (IVGTT) [[1]Hammana I. Potvin S. Tardif A. Berthiaume Y. Coderre L. Rabasa-Lhoret R. Validation of insulin secretion indices in cystic fibrosis patients.J Cyst Fibros. Dec 2009; 8: 378-381Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. In this study, we compared dynamic measures of insulin secretion during the IVGTT and surrogate indices using data from an oral glucose tolerance test (OGTT) in healthy control subjects as well as CF patients with various glucose tolerances. We found that early insulin secretion indices derived from the OGTT such as the one proposed by Stumvoll et al. (1.283+1.829×Ins30 (pmol/L)−138.7×Glyc30 (mmol/L)+3.772×Ins0 (pmol/L)) [[2]Stumvoll M. Mitrakou A Pimenta W. Jenssen T. Yki-Järvinen H. Van Haeften T. et al.Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.Diab Care. Mar 2000; 23 49: 295-301Google Scholar] or the Insulin Secretion Rate (ISR, (Ins30−Ins0) (mU/L)/(Gly30−Gly0) (mg/dL)) [[3]Scheen A.J. Paquot N. Letiexhe M.R. Castillo M.J. Lefebvre P.J. How should insulin secretion be evaluated in practice?.Diabète Métab. Dec 1995; 21: 458-464PubMed Google Scholar] can evaluate early insulin secretion in CF subjects. However, when using these OGTT-derived indices in a large database of 204 CF subjects, it appears that in 7% of cases, essentially in patients with de novo diabetes, these formulas provide negative values. In CF patients, because of significant alteration in early insulin secretion [[4]Tofe S. Moreno J.C. Maiz L. Alonso M. Escobar H. Barrio R. Insulin-secretion abnormalities and clinical deterioration related to impaired glucose tolerance in cystic fibrosis.Eur J Endocrinol. Feb 2005; 152: 241-247Crossref PubMed Scopus (77) Google Scholar], some patients demonstrate in the first 30 min of the OGTT, a rapid glucose rise without a concomitant significant insulin increase. In this situation, these formulas will provide negative values which are obviously without physiological significance and including them into an analysis raises significant methodological problems. To overpass this limitation, we reanalyzed previously published data to determine if the Area Under the Curve (AUC) obtained during time 0 to 30 min (AUC0–30) of the OGTT is also a surrogate index of early insulin secretion in CF subjects [[1]Hammana I. Potvin S. Tardif A. Berthiaume Y. Coderre L. Rabasa-Lhoret R. Validation of insulin secretion indices in cystic fibrosis patients.J Cyst Fibros. Dec 2009; 8: 378-381Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. This measure correlates significantly with early insulin secretion quantified with the IVGTT (AUC0–10) (r=0.59, p=0.021 for healthy controls subjects, r=0.50, p=0.041 for CF subjects). Therefore, this easily calculated value (AUC0–30) obtained during the OGTT can be used as a proxy of insulin secretion in CF patients. Its accuracy at various stages of the disease should however be confirmed in futures studies.

La mucoviscidose (MV) est la plus fréquente maladie létale autosomique récessive chez les Caucasiens et est due à une mutation du gène CFTR. La mutation principale est une délétion d'un acide aminé en position 508 (F508). L'espérance de vie des patients MV s'est beaucoup améliorée et conséquememment de nouvelles complications telles que le diabète lié à la MV ont vu le jour (CFRD). Des études ont montré que les femmes et les sujets homozygotes pour la mutation ΔF508 ont un plus grand risque de développer le CFRD. Cependant, très peu d'études ont examiné l'effet du genre et du génotype sur la sécrétion d'insuline. Le but principal de cette étude était donc de comparer la sécrétion d'insuline entre les hommes et les femmes avec des génotypes différents. 196 sujets adultes non diabétiques ont été recrutés dans la clinique de MV du CHUM. Leurs génotypes ont été extraits de leurs dossiers médicaux. Tous les sujets ont subi une hyperglycémie provoquée oralement (HGPO) afin de déterminer leur tolérance au glucose : tolérance normale (NGT), intolérance (IGT) ou diabète. Des échantillons de sang ont été prélevés toutes les 30 min pendant 2 h pour mesurer les niveaux d'insuline. La sécrétion d'insuline et la sensibilité ont été évaluées à l'aide d'indices connus tels que le Stumvoll. À excursion glycémique comparable, les valeurs d'insuline varie entre les génotypes et entre les genres : les hétérozygotes et les femmes ont une sécrétion d'insuline plus élevée que les homozygotes et les hommes. Le suivi prospectif sur 2 ans indique que cette insulinémie élevée semble protéger de la dégradation de l'état glycémique des patients. Dans un groupe important de patients MV, sans diagnostic antérieur de diabète, on observe une association entre une sécrétion d'insuline plus élevée et l'état hétérozygote pour la mutation F508 et/ou le genre.