Adèle Coriati

Agreement of bioelectric impedance analysis and dual-energy X-ray absorptiometry for body composition evaluation in adults with cystic fibrosis

Malnutrition in cystic fibrosis (CF) is associated with increased mortality and can lead to fat-free (FFM) and fat mass (FM) loss. Dual-energy X-ray absorptiometry (DXA) is used and validated to measure FFM and FM. DXAs high cost has led to the utilization of less costly techniques such as bioelectrical impedance analysis (BIA). The aim of this study was to determine the agreement of FFM, FM and %FM measurements taken with DXA and BIA in adults with CF. We measured FFM, FM and %FM in 34 adults with CF with a leg-to-leg BIA and an iDXA and determined agreement using Bland-Altman analysis. While DXA and BIA measurements were well correlated (r > 0.8), mean biases between both methods were between 8 and 11%. BIA underestimated FM and %FM and overestimated FFM. In a clinical research setting where these measurements are used to phenotype patients, BIA cannot replace DXA.

Characterization of patients with cystic fibrosis presenting an indeterminate glucose tolerance (INDET)

BACKGROUND CFRD is preceded and associated with a significantly increased morbidity and mortality. We aimed to characterize a large newly established glucose tolerance subgroup named INDET (indeterminate; 1-h oral glucose tolerance test (OGTT)>11.0 but 2h-OGTT<7.8 mmol/L) in adult patients with cystic fibrosis (CF). METHODS All CF participants (n=252, ≥18 yrs without CFRD) underwent a 2h-OGTT with glucose and insulin sample measurements every 30 min. They were then classified as having either normal, impaired, or INDET glucose tolerance, or de novo CFRD. Other clinical characteristics were collected such as the BMI and pulmonary function. RESULTS All groups were of similar age (P=0.629) and BMI (P=0.813). We found that the INDETs displayed decreased lung function comparable to de novo CFRD. OGTT-derived glucose or insulin secretion/sensitivity parameters cannot fully explain this observation. CONCLUSIONS Prospective studies are required to establish if the INDET-CF group can identify clinically relevant outcomes.

Glycated hemoglobin cannot yet be proposed as a screening tool for cystic fibrosis related diabetes

With improved life expectancy of cystic fibrosis (CF) patients, CF-related diabetes (CFRD) has become a major complication. The oral glucose tolerance test (OGTT) is the standard test to detect it. However, the use of OGTT is controversial, in addition to being a burden for patients and the treatment team. Research to find alternative ways of testing is ongoing. While some propose that glycated hemoglobin (HbA1c) may be an effective alternative, our past results suggest otherwise. A new analysis involving the OGTT and HbA1c values of 207 patients, between 2004 and 2015, proposes that the threshold of a lower value of HbA1c of ≥5.8%(39.9 mmol/mol) gives a sensitivity of 68.2% and a specificity of 60.5%. With such sensitivity to identify patients in need of an OGTT, 31.8% of CFRD diagnosis would be missed if the suggested HbA1c value of ≥5.8% was used as a screening tool to identify patients in need of OGTTs. Considering our results, we believe the HbA1c does not possess the characteristics of a suitable screening test for CFRD.

Could T cells be involved in lung deterioration and hyperglycemia in cystic fibrosis

Cystic fibrosis-related diabetes (CFRD) is the most frequent complication of cystic fibrosis (CF) and associated with increased mortality. Why patients have an accelerated loss of lung function before the diagnosis of CFRD remains poorly understood. We reported that patients with or without CFRD had increased glucose excursions when compared to healthy peers. Studies have demonstrated that patients with CF have increased glucose fluctuations and hyperglycemia and that this may affect the clinical course of CF and lead to lymphocyte dysfunction. T-helper 17 (Th17) lymphocytes produce and secrete the pro-inflammatory cytokine IL-17. The Th17 pathway is involved in CF lung inflammation, β-cell destruction in type 1 diabetes (T1D) and Th17 cells of patients with type 2 diabetes have increased production of IL-17 when compared to healthy peers. Also, regulatory T-cells (Tregs) have been shown to be dysfunctional and produce IL-17 in T1D. Furthermore, vitamin D can affect inflammation in CF, diabetes and the differentiation of lymphocytes. In this review, we discuss the potential roles of hyperglycemia on Th17 cells, Tregs and IL-17 as a potential cause for accelerated lung function decline before CFRD and how this could be modulated by vitamin D or by directly intervening in the IL-17A pathway.

Screening for Cystic Fibrosis-Related Diabetes: Matching Pathophysiology and Addressing Current Challenges

Nearly 50% of adult patients with cystic fibrosis (CF) have diabetes. The occurrence of CF-related diabetes (CFRD) is preceded and is associated with deterioration of lung function and nutritional status. Microvascular complications can occur, but the main cause of death is respiratory failure rather than cardiovascular causes as in type 1 or type 2 diabetes. Because other methods such as glycated hemoglobin (A1C) levels are less sensitive in patients with CF, the recommended screening test is the oral glucose tolerance test (OGTT) with a 75 g glucose dose. However, OGTT is poorly suited for patients with CF, who are already facing a high disease-care burden, and appropriate CF-glucose cut-off for diagnosis and prognosis are also questioned. Thus, alternative screening methods are compared to the classical test (2-hour OGTT), including shorter OGTTs and continuous glucose monitoring. Moreover, many challenges complicate the screening for diabetes such as the complex medical care time for a patient, which is reflected by low adherence to screening tests. The best screening test should take into account the particularities of CFRD and the complexity of the CF medical care.

Diagnosis of cystic fibrosis-related glucose abnormalities: Can we shorten the standard oral glucose tolerance test?

Adult patients with cystic fibrosis (APCF) are at high risk of developing impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) and thus an annual screening with a 2-h oral glucose tolerance test (OGTT) is recommended. This population would greatly benefit from a simplified and harmless alternative to the standard OGTT. Thus, we aimed to compare the diagnostic values of HbA1c and glycemias at interval time points during the 2-h OGTT for IGT and CFRD detection in APCF. To do so, we conducted a cross-sectional analysis of 194 APCF with normal fasting plasma glucose values (≤ 7.0 mmol · L(-1)) who underwent a 2-h OGTT. Receivers operating characteristic area under the curves (ROC-AUC) were analyzed to assess the diagnostic value of HbA1c and intermediate OGTT glycemias using 2-h OGTT glycemia as reference. For both IGT and CFRD diagnoses, ROC-AUC values obtained from glycemia at 90 min were significantly higher than HbA1c and remaining intermediate glycemias (p < 0.001). The best 90-min OGTT cut-off values for these diagnoses were >9.3 mmol · L(-1) (IGT) and ≥ 11.5 mmol · L(-1) (CFRD). A 90-min OGTT glycemia might be a simplified alternative to 2-h OGTT glycemia for earlier glucose tolerance abnormalities diagnosis in APCF. This finding should be confirmed in other APCF cohorts and its predictive value should be established prospectively.

Combined Exercise Training Improves Glycemic Control in Adult With Cystic Fibrosis.

Purpose Glucose abnormality and diabetes are the most common comorbidities in cystic fibrosis (CF). Combined (aerobic and resistance) exercise program in type 2 patients with diabetes demonstrated an improvement of glycemic control. The aim of the study was to determine whether a combined exercise program is beneficial to improve plasma glucose at 2 h of the oral glucose tolerance test in CF. Method Eighteen adults with CF with glucose abnormality were recruited (Clinicaltrial.gov: NTC02127957), and 17 were randomly assigned to a control or exercise group for 12 wk. V˙O2max, oral glucose tolerance test, muscular endurance and strength, and quality of life were measured pre- and postintervention. Results Fourteen participants completed the protocol. Patients in the exercise group improved significantly their 2-h plasma glucose values (−2.34 ± 1.26 mmol·L−1, P < 0.007, confidence interval = 99.22%) and presented a reduction of 17.2% (P < 0.05) in total glucose excursion. No significant change for other parameters was observed. Conclusion A combined exercise program improves glycemic control in CF.

Variation of glucose tolerance in adult patients with cystic fibrosis: What is the potential contribution of insulin sensitivity?

BACKGROUND Reduced insulin secretion is a key factor to explain high prevalence of glucose intolerance in patients with cystic fibrosis (CF). However, the role of insulin sensitivity remains unclear. The aim of this study is to investigate the association of insulin secretion and sensitivity with the evolution of glucose tolerance. METHODS A total of 152 patients without known diabetes from the Montreal CF cohort underwent two 2-h oral glucose tolerance tests (OGTT) at baseline and again after 21.2±5.5months. Pulmonary function and anthropometric measurements were also collected at each visit. At both visits, based on their OGTT results, patients were categorized in glucose tolerance groups (normal glucose tolerance, impaired glucose tolerance or CF-related diabetes) and stratified in 3 groups according to the variation of their glucose tolerance: stable, improved or deteriorated. RESULTS At baseline, patients in the deteriorated group had a better sensitivity to insulin than those in the improved group (P=0.029). At follow-up glucose tolerance remained stable in 55.3%, improved in 14.5% and deteriorated in 30.3% of patients. During follow-up, insulin secretion remained stable in all 3 groups. While insulin sensitivity remained stable in patients without changes in glucose tolerance it worsened in patients who deteriorated glucose tolerance (P<0.001) and improved in patients who improved their glucose tolerance (P=0.003). CONCLUSION In a context of significantly reduced insulin secretion, variations of insulin sensitivity are associated with variations of glucose tolerance in adult patients with CF.

Association between serum YKL-40 level and dysglycemia in cystic fibrosis.

BACKGROUND YKL-40, a chitinase-like protein, is a biomarker for type 1 and type 2 diabetes prognosis. We hypothesized that YKL-40 protein levels are elevated in CF patients with dysglycemia. METHODS Seventeen healthy control subjects and 66 CF patients were prospectively recruited and subjected to an oral glucose tolerance test. In all participants, fasting serum YKL-40 was compared between control and CF patients and between normal glucose-tolerant patients (NG-CF) and CF patients with dysglycemia (DG-CF). A Botnia clamp procedure was performed on a subset of patients for each group to determine the impact of acute increases of either glucose or insulin on YKL-40 concentration. RESULTS CF patients had higher serum YKL-40 values than the controls (113 [49;288] vs. 38 [30;50] ng/ml, p<0.001). YKL-40 concentrations in CF patients were mainly increased in the DG-CF group, who had significantly higher values: 213 [93;383] vs. 67 [27;97] ng/ml in the NG-CF group, p<0.001). No significant modulation of YKL-40 concentration was observed in serum of CF (NG or DG-CF) or non-CF patients, after acute exposure to glucose or insulin. CONCLUSIONS Higher serum YKL-40 levels in CF patients are significantly associated with dysglycemia. The increase in YKL-40 is potentially associated with an inflammatory response resulting from chronic glucose intolerance or CF disease evolution.

Glucose Fluctuations are Not Modulated by the Proportion of Calories from Macronutrients or Spontaneous Total Energy Expenditure in Adults with Cystic Fibrosis

OBJECTIVES To determine the modifiable factors affecting glucose variability in people with cystic fibrosis (CF). CF-related diabetes (CFRD) is the most common complication of CF, and its presence increases morbidity and mortality in patients. Patients with CF (with and without CFRD) have potentially harmful glucose fluctuations and glucose excursions when compared to healthy adults. Carbohydrate intake and exercise have been shown to affect glycemia. Therefore, our hypothesis was that the proportion of energy from carbohydrates and total energy expenditure (TEE) would influence glucose fluctuations in adults with CF. METHODS A cross-sectional study involved 36 patients with CF, in whom continuous glucose monitoring systems were installed. Glucose fluctuations were then quantified using 3 indexes: mean amplitude of glucose excursions, standard deviation and coefficient of variation. Patients filled out a 3-day food diary to quantify energy intake and the proportions of calories from carbohydrates, fats and proteins, and they wore Sensewear Armbands to estimate spontaneous TEE and footsteps walked. Glucose tolerance status was determined using oral glucose tolerance tests. RESULTS Patients with CF with normal and impaired glucose tolerance had fewer glucose fluctuations than patients with CFRD (p<0.05). However, linear regression models used to determine whether nutrition or energy expenditure affects glucose fluctuations demonstrated that energy, the proportion of carbohydrates, of fat and of protein, TEE or the number of footsteps walked did not affect glucose fluctuation indexes (p>0.05). CONCLUSIONS TEE and the proportion of energy from carbohydrates did not affect glucose fluctuations in adults with CF.