Impact of sex on insulin secretion in cystic fibrosis.

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.

Hypertriglyceridemia is associated with insulin levels in adult cystic fibrosis patients.

BACKGROUND: Recent studies have identified hypertriglyceridemic cystic fibrosis patients (CF-TG). However, whether hypertriglyceridemia is associated with an altered metabolic profile remains unknown. OBJECTIVE: To characterize CF-TG and determine whether triglycerides (TG) levels are associated with metabolic alterations. METHODS: 210 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. RESULTS: The 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. CONCLUSION: TG 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.

LDL-cholesterol and insulin are independently associated with body mass index in adult cystic fibrosis patients.

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)