Feasibility and accuracy of at-home glucose tolerance tests for cystic fibrosis related diabetes screening.

BACKGROUND: Adult people living with Cystic Fibrosis (CF) undergo annual screening for CF-related diabetes. These tests represent a burden and can lead to undesirable effects resulting in low adherence. The objectives of this study were to 1) compare gold-standard in-hospital oral glucose tolerance testing (OGTT) with at-home options, and 2) evaluate acceptability of at-home options. METHODS: A total of 34 adults living with CF undertook 3 types of OGTTs in standardized conditions within two weeks: 1) in a hospital using a 75 g glucose beverage, 2) at home with the same glucose beverage, and 3) at home using a standardized quantity of candy. Glucose levels were measured prior to the OGTT, after 1 and 2 hours. Concordance of glucose measurement, side effects and general appreciation were assessed across the three options. RESULTS: Mean blood glucose was comparable among the three tests. Glucose tolerance categorization (normal, impaired glucose tolerance, or diabetes) was concordant with the hospital reference test in 59 % of participants for the glucose beverage and 75 % for the candies. Side effects were mild with all types of OGTTs, and 94 % of participants preferred the home options. Among the at-home OGTTs, the glucose beverage was preferred to the candy option. CONCLUSIONS: Home-based OGTT could be an alternative to gold standard hospital-based OGTT testing, improving adherence to annual testing and reducing costs. However, the discrepancy between various OGTT testing methods could lead to diagnosis dilemma. This approach should be tested on a larger sample size.

Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF.

People living with cystic fibrosis (pwCF) homozygous for F508del present more severe phenotypes. PwCF with compound heterozygous genotypes F508del /A455E and F508del /L206W may have milder cystic fibrosis (CF) phenotypes. We compared F508del homozygotes and common compound heterozygotes (F508del and a second pathogenic variant) in adult patients. Nutritional, pulmonary function and glucose homeostasis indices data were collected from the prospective Montreal CF cohort. Two-hundred and three adults with CF having at least one F508del variant were included. Individuals were divided into subgroups: homozygous F508del/F508del (n=149); F508del/621+1G>T (n=17); F508del/711+1G>T (n=11); F508del/A455E (n=12); and F508del/L206W (n=14). Subgroups with the F508del/L206W and F508del/A455E had a lower proportion with pancreatic exocrine insufficiency (p<0.0001), a higher fat mass (p<0.0001), and lower glucose area under the curve (AUC) (p=0.027). The F508del/L206W subgroup had significantly higher insulin secretion (AUC; p=0.027) and body mass index (p<0.001). Pulmonary function (FEV1) was significantly higher for the F508del/L206W subgroup (p<0.0001). Over a median of 7.37 years, the risk of developing CFRD in 141 patients was similar between groups. PwCF with heterozygous F508del/L206W and F508del/A455E tended to have pancreatic exocrine sufficiency, better nutritional status, improved pulmonary function and better diabetogenic indices, but this does not translate into lower risk of CF-related Diabetes.

Managing Impending Nonsevere Hypoglycemia With Oral Carbohydrates in Type 1 Diabetes: The REVERSIBLE Trial.

OBJECTIVE: Current guidelines recommend initiating treatment for nonsevere (NS) hypoglycemia with 15 g carbohydrates (CHO) at 15-min intervals when blood glucose (BG) reaches <70 mg/dL (3.9 mmol/L). Despite this recommendation, NS hypoglycemia management remains challenging for individuals living with type 1 diabetes (T1D). We aimed to assess the efficacy of 15 g CHO at higher BG levels. RESEARCH DESIGN AND METHODS: A total of 29 individuals with T1D participated in an open-label crossover study. After an inpatient subcutaneous insulin-induced decrease in BG in the fasting state, 16 g CHO was administered orally at a plasma glucose (PG) of <70 (3.9), ≤80 (4.5), or ≤90 mg/dL (5.0 mmol/L). The primary outcome was time spent in hypoglycemia (<70 mg/dL) after initial CHO intake. RESULTS: When comparing the <70 (control) with the ≤80 and ≤90 mg/dL treatment groups, 100 vs. 86 (P = 0.1201) vs. 34% (P < 0.0001) of participants reached hypoglycemia, respectively. These hypoglycemic events lasted 26.0 ± 12.6 vs. 17.9 ± 14.7 (P = 0.026) vs. 7.1 ± 11.8 min (P = 0.002), with a PG nadir of 56.57 ± 9.91 vs. 63.60 ± 7.93 (P = 0.008) vs. 73.51 ± 9.37 mg/dL (P = 0.002), respectively. In the control group, 69% of participants required more than one treatment to reach or maintain normoglycemia (≥70 mg/dL), compared with 52% in the ≤80 mg/dL group and 31% in the ≤90 mg/dL group, with no significant rebound hyperglycemia (>180 mg/dL) within the first hour. CONCLUSIONS: For some impending NS hypoglycemia episodes, individuals with TID could benefit from CHO intake at a higher BG level.

Vaccination after developing long COVID: Impact on clinical presentation, viral persistence, and immune responses.

BACKGROUND: Vaccination protects against severe COVID-19 manifestations. For those with post-COVID-19 conditions (PCC) or long COVID, the impact of COVID-19 vaccination on the evolution of symptoms, immune responses, and viral persistence is unclear. METHODS: In this prospective observational cohort study, we evaluated the number of PCC symptoms, affected organ systems, and psychological well-being scores before and after patients with PCC received COVID-19 vaccination. We simultaneously evaluated biomarkers of systemic inflammation and levels of plasma cytokines/chemokines. We measured plasma and intracellular levels of SARS-CoV-2 antigens, and immunoreactivity to SARS-CoV-2 antigens in blood. RESULTS: COVID-19 vaccination was associated with decreases in number of PCC symptoms (pre-vaccination: 6.56 ± 3.1 vs post-vaccination: 3.92 ± 4.02; P <0.001) and affected organ systems (pre-vaccination: 3.19 ± 1.04 vs post-vaccination: 1.89 ± 1.12; P <0.001), and increases in World Health Organization (WHO)-5 Well-Being Index Scores (pre-vaccination: 42.67 ± 22.76 vs post-vaccination: 56.15 ± 22.83; P <0.001). Patients with PCC also had significantly decreased levels of several pro-inflammatory plasma cytokines/chemokines after COVID-19 vaccination including sCD40L, GRO-⍺, macrophage inflammatory protein (MIP)-1⍺, interleukin (IL)-12p40, G-colony stimulating factor (CSF), M-CSF, IL-1ß, and stem cell factor (SCF). PCC participants presented a certain level of immunoreactivity toward SARS-CoV-2, that was boosted with vaccination. SARS-CoV-2 S1 antigen persisted in the blood of PCC participants, mostly in non-classical monocytes, regardless of participants receiving vaccination. CONCLUSIONS: Our study shows higher pro-inflammatory responses associated with PCC symptoms and brings forward a possible role for vaccination in mitigating PCC symptoms by decreasing systemic inflammation. We also observed persistence of viral products independent of vaccination that could be involved in perpetuating inflammation through non-classical monocytes.

A glycosylated hemoglobin A1c above 6% (42 mmol/mol) is associated with a high risk of developing Cystic Fibrosis-Related Diabetes and a lower probability of weight gain in both adults and children with Cystic Fibrosis.

OBJECTIVES: The classical glycosylated hemoglobin A1c threshold of 6.5% is an insensitive screening test for cystic fibrosis-related diabetes (CFRD). We sought to identify CF-specific A1C thresholds associated with 1) risk of progression to CFRD and 2) changes in body mass index (BMI) and forced expiratory volume (FEV1). METHODS: We studied the cross sectional and longitudinal associations between A1c, BMI, and FEV1 in 2 cohorts of 223 children (followed for up to 8 years) and 289 adults (followed for a mean of 7.5 ± 4.3 years) with CF but without diabetes at baseline and undergoing regular assessments including Oral Glucose Tolerance Test (OGTT). RESULTS: For the onset of OGTT-defined CFRD optimal A1c threshold was 5.9% in adults (sensitivity: 67% and specificity: 71%) and 5.7% for children (sensitivity: 60% and specificity: 47%). Kaplan-Meier analysis of progression to CFRD according to baseline A1C showed increased the risk of developing CFRD for A1c ≥ 6.0% in adults (P = 0.002) and ≥ 5.5% in children (p = 0.012). Temporal changes in BMI and FEV1 according to baseline A1C in adults were assessed with a linear mixed-effect model, BMI significantly increased over time in subjects with a baseline A1c < 6%, but those with a A1C ≥ 6.0% gained significantly less weight over time (P = 0.05). There was no difference in FEV1 according to baseline A1c category. CONCLUSION: An A1C above 6% may be associated with a high risk of developing CFRD and a lower probability of weight gain in both adults and children with CF.

Canadian Cystic Fibrosis-related Diabetes Clinical Practice Survey: Analysis of Current Practices and Gaps in Clinical Care.

OBJECTIVES: Our aim in this study was to identify challenges and gaps in Canadian practices in screening, diagnosis, and treatment of cystic fibrosis-related diabetes (CFRD), with the goal of informing a Canadian-specific guideline for CFRD. METHODS: We conducted an online survey of health-care professionals (97 physicians and 44 allied health professionals) who care for people living with CF (pwCF) and/or CFRD (pwCFRD). RESULTS: Most pediatric centres followed <10 pwCFRD and adult centres followed >10 pwCFRD. Children with CFRD are usually followed at a separate diabetes clinic, whereas adults with CFRD may be followed by respirologists, nurse practitioners, or endocrinologists in a CF clinic or in a separate diabetes clinic. Less than 25% of pwCF had access to an endocrinologist with a special interest or expertise in CFRD. Many centres perform screening oral glucose tolerance testing with fasting and 2-hour time points. Respondents, especially those working with adults, also indicate use of additional tests for screening not currently recommended in CFRD guidelines. Pediatric practitioners tend to only use insulin to manage CFRD, whereas adult practitioners are more likely to use repaglinide as an alternative to insulin. CONCLUSIONS: Access to specialized CFRD care may be a challenge for pwCFRD in Canada. There appears to be wide heterogeneity of CFRD care organization, screening, and treatment among health-care providers caring for pwCF and/or pwCFRD across Canada. Practitioners working with adult pwCF are less likely to adhere to current clinical practice guidelines than practitioners working with children.

Acute soluble fibre supplementation has no impact on reducing post-prandial glucose excursions in adults with cystic fibrosis and glucose intolerance.

BACKGROUND: Cystic fibrosis (CF)-related diabetes (CFRD) is a common comorbidity in CF. In CFRD, fasting blood glucose level is often normal, but post-prandial glycaemia (PPG) is problematic. Elevated PPG has been associated to a higher risk of developing CFRD, a worst clinical state and a lower pulmonary function. Interventional studies in type 2 diabetes have demonstrated a beneficial impact of fibre supplement on PPG. METHODS: Our objective is to evaluate the efficiency of 2 doses of a soluble fibre supplement to lower PPG in CF patients with glucose intolerance (pre-diabetic or CFRD patients). This is a double-blinded crossover interventional study with three interventions: placebo or psyllium fibre (5.1g or 7.7g) of soluble fibre consumed before breakfast. A second meal (lunch) is also eaten four hours later to evaluate a second meal effect. Blood glucose and insulin were measured during the interventions. RESULTS: In 14 adult CF patients with impaired glucose tolerance (IGT; n=10) or CFRD (n=4), we observed no beneficial effect of fibre supplementation on PPG for both meals. However, all blood glucose levels were lower after the lunch compared to breakfast in spite of the higher carbohydrate content. CONCLUSION: An acute treatment with fibre supplementation had no effect on blood glucose control in patients with CF-IGT or CFRD.

Low vitamin K status in adults with cystic fibrosis is associated with reduced body mass index, insulin secretion, and increased pseudomonal colonization.

Patients with cystic fibrosis (CF) are at high risk of fat-soluble vitamin deficiencies, even with supplementation. The contribution of a suboptimal vitamin K status to respiratory and endocrine pathophysiology in CF has been inadequately characterized. This is a cross-sectional study in adult CF patients (≥18 years old) from the Montreal Cystic Fibrosis Cohort. Vitamin K1 (VK1) was measured with high-performance liquid chromatography, using fasted serum samples collected during an oral glucose tolerance test (OGTT: 2 h with plasma glucose and insulin every 30 min) (n = 168). Patients were categorized according to VK1 status (suboptimal defined as <0.30 nmol/L). Suboptimal VK1 levels were observed in 66% of patients. Patients with a suboptimal VK1 status have a higher risk of colonization with Pseudomonas aeruginosa (p = 0.001), have lower body mass index (BMI) (p = 0.003), and were more likely to have exocrine pancreatic insufficiency (p = 0.002). Using an established threshold for VK1, we did show significantly reduced OGTT-derived measures of insulin secretion in patients with a VK1 status below 0.30 nmol/L (first- and second-phase area under the curve (AUC)INS/GLU (p = 0.002 and p = 0.006), AUCINS (p = 0.012) and AUCINS/GLU (p = 0.004)). Subclinical vitamin K deficiency is more common than other fat-soluble vitamin deficiencies in patients with CF. We demonstrate an association between a suboptimal VK1 status and measures of insulin secretion. We highlight the potential associations of mild vitamin K deficiency with pseudomonal colonization and lower BMI, although these need to be validated in prospective studies.

Cystic Fibrosis-Related Diabetes: Clinical approach and knowledge gaps.

Cystic Fibrosis-Related Diabetes (CFRD) is a unique type of diabetes mellitus that shares some features with both type 1 and type 2 diabetes. Yet, its distinguishing feature of acute pulmonary complications associated with hyperglycemia and the catabolic metabolism associated with a relative insulin deficiency poses challenges to the application of traditional definitions and treatments for diabetes mellitus. People with CF (pwCF) undergo rigorous annual screening starting at age 10, a process that is challenging for patients and limited by sensitivity, specificity, and reproducibility. As pwCF continue to live longer, over 50% are expected to develop CFRD over their lifetime, including up to 20% of adolescents. Increasing numbers of people with CFRD will make this disease increasingly relevant to diabetes practitioners. Evidence-guided practice in CFRD care is limited by small and short studies. Our current understanding of CFRD may change significantly with the recent introduction of CF Transmembrane Regulator (CFTR) modulator medications. This review will explore current challenges in the diagnosis and management of CFRD, specifically highlighting knowledge gaps in the pathophysiology of CFRD, optimal screening methods, priorities for research and provide guidance with regards to screening, diagnosis, and treatment.

Insulinogenic index and early phase insulin secretion predict increased risk of worsening glucose tolerance and of cystic fibrosis-related diabetes.

OBJECTIVE: Measures of stimulated insulin secretion are emerging as important predictors of diabetes mellitus in at-risk populations. We analyzed the utility of clinical estimates of insulin secretion in a prospective cohort at risk for cystic fibrosis-related diabetes (CFRD). METHODS: We divided the profiles of 189 people with CF (pwCF) followed longitudinally in the Montreal CF cohort (mean follow up 6.6 ± 1.2 years) according to quartiles of the insulinogenic index (IGI; (I30-I0)/(G30-G0)); area under the curve for insulin normalized for glucose (AUCins/glu), and HOMA-B at baseline to compare clinical characteristics and risk of CFRD according to quartiles for each measure. We also compared characteristics of 40 pwCF found to have de novo CFRD at baseline. RESULTS: At baseline, IGI and AUCins/glu were lower in subjects with de novo CFRD and those who later developed CFRD than those who never developed CFRD (p < 0.0001 for each). Subjects with the lowest quartiles of IGI, AUCins/glu, and AUCins/glu 0-30 had increased risk of developing CFRD by Kaplan-Meier analysis (p = 0.0244, p = 0.0024, and p = 0.0338, respectively). There was no significant difference in risk between quartiles of HOMA-B. Subjects in the lowest quartile of IGI showed a significant increase in 2-hour OGTT glucose and AUCglu between the initial and final study visits (p = 0.0027 and p = 0.0044, respectively). CONCLUSION: IGI is easily measured in a clinical setting and needs to be validated in prospective studies as a potential tool to improve risk stratification in CFRD with direct relevance to pathogenesis.

Marginal association of fasting blood glucose with the risk of cystic fibrosis-related diabetes.

OBJECTIVES: Cystic fibrosis-related diabetes (CFRD) may be diagnosed by fasting blood glucose ≥ 7.0 mmol/L and/or glucose ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). We compared the role of fasting and stimulated glucose for diagnosis of CFRD. METHODS: We performed a cross-sectional review of the prevalence of fasting glycemic abnormalities and Kaplan-Meier survival analysis of risk of progression to CFRD according to baseline fasting glucose in the prospective Montreal Cystic Fibrosis Cohort. RESULTS: Isolated fasting hyperglycemia was detected in only 8% of participants at study onset. Eighty percent of subjects had isolated post-challenge hyperglycemia on their first OGTT meeting criteria for CFRD. Kaplan Meier survival analysis demonstrated that impaired fasting glucose (IFG) alone is not a risk factor for CFRD. Subjects with combined IFG and impaired glucose tolerance at baseline (IGT) had the highest risk of progression to CFRD. CONCLUSION: Post-prandial elevations in blood glucose are more common at diagnosis of CFRD. While IGT is a significant risk factor for CFRD, IFG alone is uncommon and does not increase the risk of CFRD. Patients with both IGT and IFG have the highest risk of CFRD.

Prevalence of Post-Glucose Challenge Hypoglycemia in Adult Patients With Cystic Fibrosis and Relevance to the Risk of Cystic Fibrosis-Related Diabetes.

OBJECTIVES: The clinical relevance of fasting and postprandial hypoglycemia in patients with cystic fibrosis (CF) is poorly characterized. Our aim in this study was to characterize the prevalence of hypoglycemia in adult patients during oral glucose tolerance test (OGTT) screening and determine its impact on the risk of developing CF-related diabetes (CFRD). METHODS: We analyzed 2 cohorts of pancreatic insufficient patients with CF exposed to comparable treatment recommendations in France (Lyon CF cohort [DIAMUCO]) and Canada (Montréal CF cohort [MCFC]). Patients were classified into 3 groups based on hypoglycemia absence or presence as well as its severity at baseline. We defined the groups as follows: level 2 hypoglycemia (L2H; plasma glucose [PG]<3.0 mmol/L), level 1 hypoglycemia (L1H; PG 3.0 to <4.0 mmol/L) and no hypoglycemia (NH) during an OGTT. RESULTS: A total of 153 MCFC and 114 DIAMUCO subjects were included in the study. In total, 22% of the patients experienced hypoglycemia, with 5% having it on 2 or more OGTTs. The L1H and L2H groups tended to have a lower 2-hour glucose and higher early-phase insulin secretion (insulin area under the curve at 0 to 30 minutes) compared with NH patients. In both cohorts, a greater proportion of men and patients with normal glucose tolerance had hypoglycemia. Over a 5-year period, there were no cases of CFRD in the L2H group, whereas 4 subjects in the L1H group and 36 in the NH group developed CFRD. CONCLUSIONS: Patients with hypoglycemia were at lower risk of developing CFRD, but at higher risk of early-phase insulin secretion and unsuppressed insulin secretion. This could potentially lead to further hypoglycemia after the 2-hour OGTT, suggesting high clinical relevance.

Combined Indeterminate and Impaired Glucose Tolerance Is a Novel Group at High Risk of Cystic Fibrosis-Related Diabetes.

BACKGROUND: Indeterminate glycemia (INDET) and impaired glucose tolerance (IGT) are independently associated with cystic fibrosis-related diabetes (CFRD) risk. We determined whether patients meeting both criteria have increased risk of diabetes in 2 separate adult cohorts. METHODS: The Montreal Cystic Fibrosis Cohort (MCFC; n = 293 baseline and 198 for prospective analysis excluding subjects identified with incident CFRD at baseline) and the Lyon cystic fibrosis cohort [Determination of the Predictive Factors in the Reversibility or the Aggravation in the Disorders of the Glucose Metabolism in Cystic Fibrosis Patients (DIAMUCO); n = 144/105] are prospective observational cohorts. RESULTS: In the MCFC and DIAMUCO cohorts, mean age was 25.5 ±â€…7.7 and 25.0 ±â€…8.6 years; body mass index, 21.7 ±â€…3.0 and 20.2 ±â€…2.2 kg/m2; percentage of forced expiratory volume expired in 1 sec, 73.2 ±â€…22.1 and 62.5 ±â€…21.9; and follow-up, 6.9 ±â€…3.8 and 2.4 ±â€…1.2 years, respectively. In the MCFC cohort, the IGT only and combined INDET and IGT (INDET + IGT) groups had greater risk of CFRD (P = 0.0109). In the DIAMUCO cohort, there was lower diabetes-free survival in the INDET + IGT group (P = 0.0105). In both cohorts, CFRD risk ranged from 17% in normal glucose tolerance patients up to 42% to 56% in patients with INDET + IGT. CONCLUSION: Patients who meet combined criteria have a higher risk of developing diabetes probably justifying closer follow-up.

Glycated Hemoglobin as a First-line Screening Test for Cystic Fibrosis‒Related Diabetes and Impaired Glucose Tolerance in Children With Cystic Fibrosis: A Validation Study.

OBJECTIVES: Our aims in this study were to document the screening rate for cystic fibrosis‒related diabetes (CFRD) in children followed at a cystic fibrosis (CF) clinic in Canada and to evaluate the accuracy of various glycated hemoglobin (A1C) cutoffs to screen for CFRD and impaired glucose tolerance (IGT) in a pediatric CF population. METHODS: The CFRD screening rate was calculated over a follow-up period of up to 8 years among children who attended the CF clinic between 1993 and 2018. Test performance of A1C at various thresholds ranging from 5.5% to 6.2% was compared with the oral glucose tolerance test (OGTT) as the reference method. Children with CF aged ≥10 years with an OGTT performed within 120 days of A1C measurement were included in the analysis. RESULTS: The overall CFRD screening rate was 53.0%. A total of 256 children were included for the A1C performance analysis, of whom 8.6% had an OGTT-confirmed CFRD diagnosis. An A1C threshold of 5.8% demonstrated an optimal balance between sensitivity (90.9%) and specificity (60.7%) for CFRD screening, leading to a potential reduction of 56.3% of the annual required OGTTs. A1C demonstrated poor accuracy for identifying children with IGT. CONCLUSIONS: An A1C threshold ≥5.8% allows for identification of children requiring further CFRD investigations, which may reduce the clinical burden of children with CF without compromising the ability of early CFRD diagnosis.

Peak glucose during an oral glucose tolerance test is associated with future diabetes risk in adults with cystic fibrosis.

AIMS/HYPOTHESIS: Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis (CF) and its presence is associated with adverse effects on nutritional status and pulmonary function. Early diagnosis could minimise CFRD morbidity, yet current methods of an OGTT at 0 and 2 h yield unreliable results. Our aim was to determine which indices from a 2 h OGTT with sampling every 30 min might improve prediction of CFRD. METHODS: Cross-sectional analysis at baseline (n = 293) and observational prospective analysis (n = 185; mean follow-up of 7.5 ± 4.2 years) of the Montreal Cystic Fibrosis Cohort were performed. Blood glucose and insulinaemia OGTT variables were studied in relation to lung function (forced expiratory volume in 1 s [FEV1]), BMI and risk of developing CFRD. RESULTS: At baseline, maximum OGTT glucose (Gmax) was negatively associated with FEV1 (p = 0.003). Other OGTT values, including classical 2 h glucose, were not. A higher Gmax was associated with lower insulin secretory capacity, delayed insulin peak timing and greater pancreatic insufficiency (p < 0.01). Gmax was positively associated with the risk of developing CFRD (p = 0.0029); no individual with a Gmax < 8 mmol/l developed CFRD over the following decade. No OGTT variable correlated to the rate of change in BMI or FEV1. CONCLUSIONS/INTERPRETATION: In adults with CF, Gmax is strongly associated with the risk of developing CFRD; Gmax < 8 mmol/l could identify those at very low risk of future CFRD. Gmax is higher in individuals with pancreatic insufficiency and is associated with poorer insulin secretory capacity and pulmonary function.

Impact of 1h oral glucose tolerance test on the clinical status of adult cystic fibrosis patients over a 4-year period.

OBJECTIVE: To report the clinical profile associated with G60 and I60 over a 4-year prospective observational period in 2 large cohorts of adult patients with CF. METHODS: 319 patients were included (210 Canadian and 119 French) and classified according to their inclusion G60 (≥ or < 11.1 mmol/L) and the median inclusion I60 (≥ or < 24 mU/I). Forced expiratory volume in 1 second (FEV1), body mass index (BMI) were collected on OGTT days. Linear mixed regression models were used to assess the effect of G60 and I60. RESULTS: High G60 was not associated to a lower FEV1 at inclusion and the follow-up decline was not higher in the high G60 group (Coefficient [95% CI]: -3.4 [-7.4;0.6], p = 0.0995.). There was no significant association between BMI and G60. Patients with high I60 tended to have a higher mean BMI (+0.5 kg/m2 [0.0 to 1.1], p = 0.05) but no interaction over time was observed. CONCLUSIONS: High G60 is not associated with a lower lung function at inclusion nor its decline over a 4-year follow-up. High I60 is slightly associated to a higher weight at inclusion, but not with BMI evolution over time in adult patients.

Influence of pre-diabetic and pancreatic exocrine states on pulmonary and nutritional status in adults with Cystic Fibrosis.

BACKGROUND: In 1992, a landmark study demonstrated clinical deterioration in respiratory function and nutritional status prior to the onset of cystic fibrosis-related diabetes (CFRD). We re-evaluated this outcome. METHODS: The Montreal Cystic Fibrosis Cohort is a prospective CFRD screening study. We performed a 6-year retrospective analysis of nutritional parameters and FEV1 (%) in subjects who developed incident CFRD and in controls who maintained normoglycemia (NG). In the former group, data was collected over 6 years prior to diabetes onset. RESULTS: Subjects (n = 86) had a mean age of 31.7 ± 8.1 years, BMI of 23.0 ± 4.0 kg/m2, and FEV1% of 70.1 ± 24.2%. Eighty-one percent had pancreatic insufficiency (PI). Patients were grouped as follows: NG+PS (pancreatic sufficient) (n = 16), NG+PI (pancreatic insufficient) (n = 21), CFRD+PS (n = 3) and CFRD+PI (n = 46). At their most recent screen NG+PS subjects had significantly greater BMI, as compared to NG+PI and CFRD+PI groups (26.2 ± 3.6 kg/m2 vs 22.6 ± 4.2 kg/m2 vs 22.1 ± 3.5 kg/m2, p = 0.0016). FEV1 was significantly greater in the NG+PS group (91.5 ± 16.8% vs 67.8 ± 25.3% vs 63.5 ± 22.2%, p = 0.0002). The rates of change in weight, BMI, fat mass (%), and FEV1 prior to the most recent visit (NG+PS, NG+PI groups) or to the diagnosis of de novo CFRD were similar between groups. CONCLUSION: In a contemporary context, CFRD onset is not preceded by deterioration in BMI, fat mass, or pulmonary function. Low BMI and FEV1 are more closely associated with PI than a pre-diabetic state.

Dyslipidemia is not associated with the development of glucose intolerance or diabetes in cystic fibrosis.

BACKGROUND: A high-fat, high-calorie diet is recommended in patients with cystic fibrosis (CF) as it improves nutritional status, respiratory health and longevity. In the general population, this diet is associated with the risk of diabetes. It is unknown whether dyslipidemic changes might contribute to the development of CF-related diabetes (CFRD). OBJECTIVE: This study aimed to (i) characterize dyslipidemia and (ii) examine the association between dyslipidemia and development of glucose intolerance. METHODS: Prospective observational study with serial assessments of pulmonary function, glucose tolerance, and lipid profile. Due to intrinsically low total, HDL and LDL cholesterol in patients with CF, subjects were characterized as having dyslipidemia if they had i) HDL in the lowest quartile and/or ii) hypertriglyceridemia (≥1.7 mmol/L). RESULTS: A total of 256 patients with CF were included (age: 25.5 ±â€¯7.7 years; BMI: 21.7 ±â€¯3.0 kg/m2; FEV1%: 73.2 ±â€¯22.1%; pancreatic insufficiency: 87%). Amongst these patients, 22.7% had low HDL, 9.0% had hypertriglyceridemia and 3.9% had mixed dyslipidemia. There were no differences in HbA1c (p = 0.583) or estimated insulin resistance [HOMA-IR (p = 0.206) or Stumvoll index (p = 0.397)]. Patients with hypertriglyceridemia had higher fat mass (p = 0.038) and fewer had pancreatic insufficiency. Lipid profiles were similar between subjects with CF and subjects with de novo CFRD. There was no effect of low HDL or hypertriglyceridemia on the development of CFRD over 10 years (p = 0.683). CONCLUSION: In adult patients with CF, dyslipidemia is not associated with the risk of developing hyperglycemia or CFRD.

Overweight, obesity and significant weight gain in adult patients with cystic fibrosis association with lung function and cardiometabolic risk factors.

BACKGROUND: For patients with cystic fibrosis (CF), maintaining a normal BMI is associated with better pulmonary function (FEV1) and survival. Given therapy improvements, some patients are now overweight, obese or present rapid weight gain. However, the impact of being overweight on clinical outcomes (e.g. FEV1 & metabolic complications) remains unknown. METHODS: Baseline data from 290 adult CF patients and observational follow-up (3.5 years; n = 158) were collected. BMI categories: underweight (UW < 18.5 kg/m2), normal (NW 18.5-26.9 kg/m2), and overweight/obese (OW ≥ 27 kg/m2). Follow-up data (weight change over time): weight loss (WL>10%), stable (WS), and weight gain (WG>10%). BMI categories and follow-up data were compared to FEV1 and cardiometabolic parameters: glucose tolerance, estimated insulin resistance (IR), blood pressure (BP), and lipid profile. RESULTS: For BMI categories, 35 patients (12.1%) were UW, 235 (81.0%) NW, and 20 (6.9%) OW. Compared to UW and NW patients, OW patients are older (p < 0.001), had less pancreatic insufficiency (p = 0.009), a higher systolic BP (p = 0.004), higher LDL (p < 0.001), and higher IR (p < 0.001). Compared to UW patients, OW patients had a better FEV1 (p < 0.001). For weight change, WL was observed in 7 patients (4.4%), WS in 134 (84.8%) and WG in 17 patients (10.8%). Compared to WL and WS patients, WG patients had a 5% increase in FEV1 accompanied by higher IR (p = 0.017) and triglycerides (p < 0.001). No differences were observed for glucose tolerance for neither BMI nor weight change. CONCLUSION: A higher weight or weight gain over time are associated with a better FEV1 but also some unfavorable cardiometabolic trends.

Hepatic enzyme ALT as a marker of glucose abnormality in men with cystic fibrosis.

AIM: Cystic fibrosis (CF) patients are at high risk of developing CF-related diabetes (CFRD). In non-CF patients, liver disease, specifically steatosis and non-alcoholic fatty liver disease (NAFLD), is strongly associated with type 2 diabetes. We compared glycemic status and metabolic profiles in CF patients according to a biomarker of hepatic injury, alanine aminotransferase (ALT). METHODS: We conducted a cross-sectional study among 273 adult CF patients recruited from the Montreal CF Cohort. A 2-hour oral glucose tolerance test (OGTT) was performed to collect glucose and insulin measures every 30 minutes. Fasting ALT levels and anthropometric measures were also obtained. Patients were categorized into 2 groups based on ALT cut-off of 25 U/L. RESULTS: Patients in the high ALT group were mostly men (83%), had higher mean weight and BMI (p<0.001) and showed elevated glucose levels throughout OGTT (p≤0.01). When stratified by sex, only men with high ALT showed significantly higher weight (p<0.001), higher glycemic values at 60, 90 and 120 minutes of OGTT (p≤0.01), higher frequency of de novo CFRD (20.5% vs 8.2%, p = 0.04) as well as lower insulin sensitivity than men with normal ALT (p = 0.03). ALT levels were strongly associated with HOMA-IR in CFRD patients (p = 0.001, r2 = 0.28). CONCLUSIONS: Adult CF men with higher ALT show an increased frequency of dysglycemia and de novo CFRD, lower insulin sensitivity and higher eight. Our data suggests that ALT levels could be an interesting tool to guide targeted diabetes screening, particularly among CF men. Prospective studies are needed to confirm these observations.