Abnormal glucose metabolism in cystic fibrosis☆,☆☆,★,★★,♢

Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in patients with cystic fibrosis (CF). Prevalence of CFRD increases with age and is greater with severe mutations. Other risk factors associated with CFRD are female sex, pancreatic insufficiency, liver disease, need for gastrostomy tube feedings, history of bronchopulmonary aspergillosis, and poor pulmonary function. CFRD is related to worse clinical outcomes and increased mortality. Early diagnosis and treatment have been shown to improve clinical outcomes. Screening for CFRD is recommended with an annual oral glucose tolerance test (OGTT) starting at age 10 years. Diagnosis of CFRD is made by standard American Diabetes Association (ADA) criteria during baseline health. CFRD can also be diagnosed in individuals with CF during acute illness, while on enteral feeds, and after transplant. In this review we will discuss the epidemiology of CFRD and provide an overview of the advantages and pitfalls of current screening and diagnostic tests for CFRD.

Deterioration of anthropometric and lung function parameters was shown to precede the onset of cystic fibrosis-related diabetes (CFRD) in adults. In children, studies have been conducted in small cohorts with relatively short observation period. Study objectives were to document the longitudinal trends of anthropometric, pulmonary, nutritional and metabolic parameters from cystic fibrosis (CF) diagnosis to the ascertainment of abnormal glucose tolerance and identify parameters associated with the incidence of such abnormalities in a pediatric CF cohort.

Retrospective cohort study of 281 children with CF. Longitudinal trends of anthropometric, lung function, nutritional and metabolic data were generated from CF diagnosis to the ascertainment of abnormal glucose tolerance defined as the presence of either impaired glucose tolerance (IGT), unconfirmed CFRD or CFRD. Cox models and Kaplan–Meier curves were used to identify factors associated with developing abnormal glucose tolerance.

Forty-five percent of cohort had normal glucose tolerance (NGT), 27% IGT, 10% unconfirmed CFRD and 18% CFRD. Children who developed CFRD displayed lower height z-scores from a very early age. Conversely, HbA1c levels began to rise closer to CFRD ascertainment. Height z-scores (HR: 0.45; CI 95% [0.29–0.69]) and HbA1c (HR: 2.43; CI 95% [1.86–3.18]) in years preceding ascertainment were associated with the risk of developing CFRD.

Children who developed CFRD display distinctive trends for height z-scores from a very early age, whereas HbA1c appears as a marker of established glucose metabolism derangements.

La survenue d’une grossesse chez une patiente atteinte de mucoviscidose est une éventualité de plus en plus fréquente compte tenu des avancées thérapeutiques et de l’augmentation de la proportion de patientes en âge de procréer. Les premières publications étaient très pessimistes sur le devenir d’une patiente enceinte lorsqu’elle en est atteinte. Elles ont rapporté une diminution des capacités respiratoires et de la survie maternelle à la suite de la grossesse, ainsi qu’une augmentation importante de la morbidité fœtale. Actuellement, les études récentes sont plutôt encourageantes. L’objectif de cette mise au point est d’évaluer, à travers une revue de la littérature récente, les conséquences de la grossesse sur les différents aspects de la maladie et inversement le retentissement de la mucoviscidose sur le déroulement de la grossesse ce afin d’apporter un conseil médical approprié à ces patientes et d’adapter leur prise en charge obstétricale.

As a result of improvements in life expectancy and therapies, increasing numbers of patients with cystic fibrosis become pregnant. The first studies were pessimistic and report adverse outcomes on the fetus and the mother. In the recent publications, long-term outcome for women with cystic fibrosis does not appear to be negatively impacted by pregnancy. Furthermore, the number of women successfully completing pregnancy continues to rise. The aim of this review is to assess the outcome of pregnancy in women with cystic fibrosis and the impact of pregnancy on the disease. It is hoped it will improve the counseling for pregnant women with cystic fibrosis and their obstetrical management.

Screening for Cystic Fibrosis-related diabetes is recommended in patients with CF <10 years old when there are concerns about growth and lung function. The Oral Glucose Tolerance Test (OGTT) is recommended but has not been validated in this cohort. We sought to determine whether the 2-h OGTT, the gold standard diagnostic test for CFRD, detects clinical decline in children with CF <10 years old.

We analysed blood glucose(BG) levels collected every 30 min during OGTT in 27 children with CF < 10 years old, comparing the 2-hour BG (BG_120min), peak BG (BG_max) and Area Under the Curve(AUC) for glucose and the association with lung function and nutritional status. We also compared the OGTT results with results from Continuous Glucose Monitoring (CGM) performed in 11 participants.

The BG_max was higher than the BG_120min in 25/27 (93%) participants. There was a significant inverse correlation between BG_max and weight z-score (r_s = −0.56, p = .002) and between BG_max and FEV₁ (r_s = −0.54, p = .014) that was not present for BG_120min. A significant inverse correlation was also identified between fasting insulin level and elevated glucose on CGM, defined as AUC >7.8 mmol/L (r_{s =} − 0.69, p = .027) or as % time > 7.8 (r_s = − 0.76, p = .011).

Children with CF < 10 years of age with higher BG_max on OGTT have lower lung function and weight z- scores that may not be identified using the 2 h OGTT BG_120min. CGM also identifies glucose excursions in young children with CF.

Cystic Fibrosis Related Diabetes Mellitus (CFRD) drives excess pulmonary morbidity and mortality in patients with cystic fibrosis (CF). The recommended treatment is insulin therapy. Insulin therapy in CF should be customized to the specific patient. CF patients typically require intensive insulin regimens such as multiple daily injections or insulin pump therapy, but frequently require lower doses than in type 1 diabetes mellitus. Patients with CF may also need insulin to cover intravenous or enteral feedings. Pre-diabetic glycaemic abnormalities are also associated with clinical decline in cystic fibrosis prior to the diagnosis of CFRD, however, whether and how this should be treated is not fully determined. There is also interest, but inadequate data regarding other treatments besides insulin (i.e., oral medications) for treatment of pre-diabetes or CFRD. CFTR potentiator and corrector therapy has yet to demonstrate an effect on the rate of CFRD, but may improve insulin secretion. There is great opportunity for further research to better understand when and how best to treat glycaemic abnormalities in cystic fibrosis.

Aging cystic fibrosis (CF) patients are at high risk of developing CF-related diabetes (CFRD). Decrease in insulin secretion over time is the main hypothesis to explain this increasing prevalence but mechanisms are still not well elucidated. The objective is to assess evolution of glucose tolerance and insulin secretion/sensitivity in aging CF patients.

This is a retro-prospective observational analysis in the older adult CF patients from the Montreal Cystic Fibrosis Cohort (n = 46; at least 35 years old at follow-up) and followed for at least 4 years. Baseline and follow-up (last visit to date) 2-h oral glucose tolerance test (OGTT with glucose and insulin measurements every 30 min) were performed. Pulmonary function test (FEV₁) and anthropometric data were measured the same day. Insulin sensitivity was measured by the Stumvoll index.

After a mean follow-up of 9.9 ± 2.6 years, mean age at follow-up was 43.5 ± 8.1 years old. An increase of body weight (+2.6 ± 6.5 kg, p = 0.01) and a decrease in pulmonary function (FEV₁; 73.4 ± 21.2% to 64.5 ± 22.4%, p ≤ 0.001) were observed. Overall, insulin secretion is maintained at follow-up but all OGTT glucose values increased (for all values, p ≤ 0.028). At follow-up, 28.3% of patients had a normal glucose tolerance while 71.7% had abnormal glucose tolerance (AGT). AGT patients decreased their insulin sensitivity over time (p = 0.029) while it remained the same in NGT patients (p = 0.917).

In older CF patients, the progression of impaired glucose tolerance is occurring with stable insulin secretion but reduced insulin sensitivity.