Cystic Fibrosis-related Diabetes Patients Research Articles

Glycemic Variability and the Thickness of Retinal Layers in Cystic Fibrosis Patients with and without Cystic Fibrosis Related Diabetes

Purpose Patients with cystic fibrosis (CF) are at risk to develop CF related diabetes (CFRD) and subsequently even diabetic neuro- and/or vasculopathy. We sought to determine if there are typical signs of diabetes-related retinal alterations present in CF patients with preserved and impaired glycemic control. Methods During routine annual examination CF patients were offered an additional 7-day period of real time continuous glucose monitoring (rtCGM) and an ophthalmological examination including retinal optical coherence tomography (OCT). Patients were categorized according to the glycemic control, i.e. the results of an oral glucose tolerance test (OGTT) and rtCGM were taken into consideration. OCT data was analyzed by our previously published visual analysis software generating dedicated and spatially resolved deviation maps for visualization and quantification of differences in total retinal thickness and thickness of retinal nerve fiber layer (RNFL) as well as ganglion cell layer (GCL) in comparison to age-matched healthy controls and patients with either type 1 or type 2 diabetes mellitus. Results Results of the rtCGM and/or OGTT enabled discrimination between patients with normal glycemic control (CFNG; n = 6), with abnormal glycemic control (CFAG; n = 6) and overt CFRD (n = 4). OCT data indicates gradually increasing retinal thinning in all 3 groups, depending on the degree of glucose metabolism disorder compared to healthy controls. At the foveal region total retinal thickness and GCL thickness were significantly thinner in CFRD patients compared to CFNG patients (total retinal thickness: 260.4 µm (239.3–270.8) vs. 275.4 µm (254.3–289.5); GCL: 11.82 µm (11.16–15.25) vs. 17.30 µm (13.95–19.82); each p < 0.05). Conclusion Although we investigated a rather small number of patients, we obtained evidence that intraretinal neurodegenerative changes occur in each of our subgroups (CFNG, CFAG, CFRD). Beyond this, our results favor the detrimental role of additional diabetes, as the deviations from healthy controls were most pronounced in the CFRD group and are similar to those seen in patients suffering from type 1 or type 2 diabetes.

Predicting glycemic control status and high blood glucose levels through voice characteristic analysis in patients with cystic fibrosis-related diabetes (CFRD)

Cystic fibrosis-related diabetes (CFRD) is associated with reduced life expectancy in adults with cystic fibrosis (CF). Voice analysis may be a convenient method for diagnosing and monitoring CFRD. This study aims to determine the relationship between voice characteristics and markers of glucose and glycemic control and to identify if voice analysis can predict high blood glucose levels and glycemic control in adults with CFRD. We conducted a prospective cross-sectional study in adults with CF from March to December 2021. We recorded 3-second voice samples of a sustained /a/ vowel and analyzed voice characteristic using the Computerized Speech Lab with the Multi-Dimensional Voice Program. In female participants with CFRD, the noise-to-harmonic ratio was significantly lower in those with HbA1c ≥ 7. Furthermore, fundamental frequency variation was significantly lower in both male and female participants with CFRD who had a glucose level of 200 mg/dL or higher at the time of collection. This finding was also associated with a high level of point-of-care glucose. The human voice has potential as a non-invasive tool for measuring glucose levels and glycemic control status in CFRD patients in the future.

Cystic Fibrosis-Related Diabetes in Poland.

Cystic fibrosis (CF) is the most common autosomal recessive inherited monogenic disease in Caucasians. As medical technology progresses and the quality of patient care improves, the survival time of patients with CF has increased, which results in more frequent comorbidities such as cystic fibrosis-related diabetes (CFRD). CFRD is the result of abnormal glucose metabolism characterized primarily by insulin deficiency, exacerbated periodically by insulin resistance. The aim of our study was to analyze the epidemiology of patients with CFRD in Poland on the basis of data collected from six CF treatment centers. Analyses were performed on 1157 CF patients who were treated at one of the six CF care centers. CFRD was diagnosed according to standard criteria. All data including demographics, types of CFTR mutations, CFRD duration, and microorganisms in the sputum were obtained from the patients’ medical history. Our study indicates that the prevalence of CFRD in Poland is 12.9%. CFRD was most often diagnosed between the ages of 11 and 20 (60% of patients), while 23% of patients were diagnosed between 21 and 30 years of age. Furthermore, we observed that approximately 3–5% of patients under the age of 10 had CFRD. We found out that the type of mutation did not affect the frequency of CFRD development. Factors that increased the risk of developing CFRD include underweight and chronic Pseudomonas aeruginosa infection. Due to the extended lifespan of CF patients, the number of CFRD patients is currently increasing. We believe that the results of our study may complement information from other studies or may be useful in planning health policy in Poland.

Continuous glucose monitoring indices predict poor FEV1 recovery following cystic fibrosis pulmonary exacerbations

BackgroundLittle is known about the effect of dysglycemia during cystic fibrosis pulmonary exacerbation (PEx) on recovery of FEV1 percentage predicted (ppFEV1) MethodsContinuous glucose monitoring (CGM) was commenced at the time of admission to hospital for PEx and continued for 6 weeks. The CGM indices, percentage of time glucose greater than 7.8 mmol/L (%T>7.8) and mean glucose were evaluated as predictors of absolute ppFEV1 change following treatment of PEx. ResultsOf the 20 participants who completed the study 13 (65%) had cystic fibrosis related diabetes (CFRD). The mean of both CGM indices were highest during the first week of pulmonary exacerbation and continued to decline over the first 4 weeks at which point they plateaued. Using multivariate regression models, factors which were predictive of maximum attained ppFEV1 change over 6 weeks were %T>7.8, mean glucose, HbA1c and preadmission ppFEV1 change from baseline. These relationships were independent of a diagnosis of CFRD, which was not associated with ppFEV1 recovery. In a longitudinal model of ppFEV1 change at weeks 1, 2 and 6, the CGM index %T>7.8 approached significance as a predictive variable. ConclusionsHyperglycemia during PEx in adult CF patients is associated with poorer ppFEV1 recovery. Conversely, there was no association observed between CFRD diagnosis and ppFEV1 improvement, suggesting that optimization of glycemic control in CFRD patients may positively influence recovery of lung function. Further clinical trials are required to evaluate the merits of intensive glycemic control in CFRD during PEx.

1481-P: Patients with Cystic Fibrosis–Related Diabetes Present with Specific Pancreatic Anomalies

Cystic fibrosis related diabetes (CFRD) is found in 20 to 50% of adults with cystic fibrosis (CF). Repeated oral glucose tolerance tests are used to screen for CFRD, but are not perfect indicators and can be tiresome for patients who already undergo many medical tests. We hypothesized that pancreatic imaging may differ between patients with and without CFRD and that the patients with the more “at-risk” pancreatic morphology could be followed more closely with the aim to detect diabetes early. We performed a non-matched case-control retrospective study comparing the abdominal ultrasounds (U.S.) and computed tomography (CT) (including abdominal slices of thoracic CT) of patients with CF with or without CFRD (“CFRD patients” and “CF patients”, respectively). Forty-four CFRD patients and 58 CF patients were included. Thirty-seven percent of the U.S. results were either uninterpretable or discordant with the CT results. Therefore, only the results of the CT were eventually analyzed. Seventy-one percent of CFRD patients presented with complete pancreatic involution (CPI), versus 57% of CF patients (p = 0.0016), and 98% of CFRD patients presented with at least partial pancreatic involution. Patients with CPI presented more frequently with exocrine pancreatic insufficiency than patients with a normal CT scan (95% versus 29%, p&amp;lt; 0.0001). Unexpectedly, 22% of CFRD patients presented with pancreatic calcifications, versus none of the CF patients (p = 0.0003). Patients with pancreatic calcifications did not differ from patients without, except that they were less likely to be homozygous for DeltaF508 mutation (22 versus 53%, p = 0.04). CPI is more often seen in CFRD patients than in CF patients, but is still a very frequent occurrence. A more distinctive feature is the presence of pancreatic calcifications. These might be used as a warning signal to look more closely for diabetes in patients with CF, and can be searched for on abdominal slices of routinely performed thoracic CT. Disclosure L. Alexandre-Heymann: None. M. Puerto: Other Relationship; Self; Ipsen Biopharmaceuticals. P. Burgel: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Chiesi USA, Inc., Vertex Pharmaceuticals. Consultant; Self; GlaxoSmithKline plc., Pfizer Inc., Teva Pharmaceutical Industries Ltd., Zambon. Speaker’s Bureau; Self; Novartis AG. E. Larger: None.

Repaglinide versus insulin for newly diagnosed diabetes in patients with cystic fibrosis: a multicentre, open-label, randomised trial

Cystic fibrosis (CF)-related diabetes (CFRD) impacts significantly on mortality and quality of life. Impaired glucose metabolism and CFRD are associated with poor weight and height gain and impaired lung function in children and adolescents (1). In that study, height and weight were lower in CF patients with diabetes than those without, not only at diagnosis of CFRD, but also years before that. After CFRD diagnosis, height and weight declined even further in CFRD patients. In contrast, no reduction of BMI was observed. All analyzed lung function parameters showed a marked decline in CFRD patients starting 1 year prior to CFRD diagnosis (1).

Characteristics of cystic fibrosis-related diabetes: Data from two different sources the European cystic fibrosis society patient registry and German/Austrian diabetes prospective follow-up registry.

Standardized patient registries provide a unique basis to get insight into cystic fibrosis (CF)-related diabetes (CFRD), the most common comorbidity in CF. A total of 3853 CFRD patients from the European CF Society Patient Registry (ECFSPR) and 752 from the German/Austrian diabetes prospective follow-up (diabetes patienten verlaufsdokumentation [DPV]) were studied. To adjust for age and sex, multivariable regression was used (SAS 9.4). DPV subjects were younger (26.5 [20.2-32.6] vs 28.3 [21.7-36.0] years, P < 0.001) and more often female (59.6 vs 50.9%, P < 0.001). In both registries, F508del homozygotes were most frequent, with higher proportion in DPV (80.9 vs 57.8%, P = 0.003). After adjustment, lung-transplantation (LTX) was more common in ECFSPR (18.9 vs 4.9%, P < 0.001), although duration since LTX (4.8 ± 0.2 vs 5.5 ± 0.7 years, P = 0.33) did not differ. In DPV patients without LTX, a lower BMI (19.6 ± 0.1 vs 21.0 ± 0.1 kg/m2 , P < 0.001), higher proportion of underweight (41.2 vs 20.2%, P < 0.001) and a tendency towards worse lung function (%FEV1 : 42.3 ± 4.2 vs 48.3 ± 0.5%, P = 0.16) were observed. Between both registries, demographic and clinical differences of CFRD were present. Besides different kind of data sources, diverse treatment structures between countries may play a role. The results may further indicate a more serious illness in patients treated in specialized diabetes clinics, documenting their data in DPV.

Markedly Delayed Insulin Secretion and a High Rate of Undetected Overt Diabetes Characterize Glucose Metabolism in Adult Patients with Cystic Fibrosis After Lung Transplantation

Cystic fibrosis-related diabetes (CFRD) is associated with adverse clinical outcomes and should be screened for by an annual oral glucose tolerance test (OGTT). Since pathophysiologic studies have mainly been performed in a pediatric/adolescent, nontransplanted collective, we aimed to assess parameters of insulin secretion and sensitivity in adult cystic fibrosis (CF) patients after lung transplantation (LT). Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index [BMI] 21.5 ± 3.3 kg/m2) and 8 control subjects matched by age (36.0 ± 6.6 years; P>.05), BMI (22.3 ± 1.5 kg/m2; P>.05), and gender (CON group) underwent a 3-hour OGTT with glucose, insulin, and C-peptide measurements. Parameters of insulin secretion and sensitivity as well as lipid profiles were assessed. In the CF group, 4 patients were diagnosed with overt diabetes (CFRD) compared to CF patients without diabetes (CF-noDM), of whom 6 had indeterminate glycemia with 1-h glucose values >200 mg/dL. The insulin peak after glucose load occurred after 30 minutes in CON, after 90 minutes in CF-noDM, and was missing in CFRD. Insulin sensitivity was comparable between the groups. Beta-cell glucose sensitivity was markedly reduced in CFRD (10.7 ± 5.8 pmol/min*m2*mM), higher in CF-noDM (39.9 ± 23.4 pmol/min*m2*mM), but still significantly lower compared to CON (108.3 ± 53.9 pmol/min*m2*mM; P = .0008). CFRD patients exhibited increased triglyceride levels and decreased high-density lipoprotein levels. Adult CF patients after LT have profound disturbances in glucose metabolism, with a high rate of undetected diabetes and markedly delayed insulin secretion. Curbed beta-cell glucose sensitivity rather than insulin resistance explains postprandial hyperglycemia and is accompanied by abnormalities in lipid metabolism. AUC = area under the curve; BMI = body mass index; CF = cystic fibrosis; CFRD = cystic fibrosis-related diabetes; CFTR = cystic fibrosis transmembrane-conductance regulator; CF-TX = cystic fibrosis patients who underwent lung transplantation; CGM = continuous glucose monitoring; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; INDET = indeterminate glycemia; LDL = low-density lipoprotein; LT = lung transplantation; OGIS = oral glucose sensitivity index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index.

Evaluation of Diagnosis and Management Plan of Diabetes Mellitus Related Cystic Fibrosis in Children

Background: Cystic fibrosis (CF) is a disease that occurs as a result of genetic mutations in cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR can be found in airways epithelial cells, intestine and cells with exocrine and exocrine function. CF is associated with variant complications, Cystic Fibrosis-Related Diabetes (CFRD) is considered as one of the most common complications of CF. Objective: In this review, we discussed the recent updates about Cystic Fibrosis-Related Diabetes (CFRD) diagnosis and management plan. Methods: PubMed database were used for articles selection. All relevant articles related to our review were chosen to cover the following topics: Cystic Fibrosis, Cystic Fibrosis Related Diabetes management, Cystic Fibrosis Related Diabetes diagnosis. We excluded other articles, which are not related to our objectives. Conclusion: CFRD can significantly worse the health condition of CF patients. However, with the recent advancement of management plans of CFRD, previous sex differences in mortality have disappeared and that the gap in mortality between CF patients with diabetes and CF patients without diabetes has considerably narrowed. Early diagnosis and early intervention also helped in improving the quality of CFRD patients and preventing the complications. This can be obtained by annual screening for DM among CF patients since 10 years of age using OGTT as recommended by ADA. The primary pathologic feature of CFRD is insulin insufficiency. It leads to increased breakdown of protein and fat. So, insulin replacement is the only recommended medical treatment and it has been shown to improve clinical outcomes. Oral diabetes agents are usually not recommended in CFRD.

Evaluation of Diagnosis and Management Plan of Diabetes Mellitus Related Cystic Fibrosis in Children

Background: Cystic fibrosis (CF) is a disease that occurs as a result of genetic mutations in cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR can be found in airways epithelial cells, intestine and cells with exocrine and exocrine function. CF is associated with variant complications, Cystic Fibrosis-Related Diabetes (CFRD) is considered as one of the most common complications of CF. Objective: In this review, we discussed the recent updates about Cystic Fibrosis-Related Diabetes (CFRD) diagnosis and management plan. Methods: PubMed database were used for articles selection. All relevant articles related to our review were chosen to cover the following topics: Cystic Fibrosis, Cystic Fibrosis Related Diabetes management, Cystic Fibrosis Related Diabetes diagnosis. We excluded other articles, which are not related to our objectives. Conclusion: CFRD can significantly worse the health condition of CF patients. However, with the recent advancement of management plans of CFRD, previous sex differences in mortality have disappeared and that the gap in mortality between CF patients with diabetes and CF patients without diabetes has considerably narrowed. Early diagnosis and early intervention also helped in improving the quality of CFRD patients and preventing the complications. This can be obtained by annual screening for DM among CF patients since 10 years of age using OGTT as recommended by ADA. The primary pathologic feature of CFRD is insulin insufficiency. It leads to increased breakdown of protein and fat. So, insulin replacement is the only recommended medical treatment and it has been shown to improve clinical outcomes. Oral diabetes agents are usually not recommended in CFRD.

Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function.

Impaired glucose metabolism and cystic fibrosis (CF)-related diabetes (CFRD) are associated with insufficient weight gain and impaired lung function in children and adolescents with CF. We have asked whether imminent CFRD may be a cause of poor growth in children and adolescents. A retrospective case control study including 32 patients with CF with or without diabetes was conducted. Sixteen pairs, matched according to age, gender and exocrine pancreatic insufficiency, were analysed. Standard deviation scores (SDS) of height, growth, weight, body mass index (BMI), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and forced expiratory flow at 75% of expired FVC (FEF75) were recorded during a mean observation period of 13 years per patient. SDS of height and weight were reduced in CF patients with diabetes compared to those without, not only at the point of diagnosis (both p<0.05) but years before the evidence of diabetes. Afterwards there was a significant decline in height (p<0.001) and weight (p<0.01) SDS in CFRD patients and an increasing difference between the height and weight of CF patients with or without diabetes. In contrast, no significant reduction of BMI-SDS was observed in CFRD patients. All analysed lung function parameters showed a marked decline in CFRD patients starting 1 year prior to the diagnosis of diabetes. Deteriorating growth, reduced weight and impaired lung function are related to the development of CFRD and are obvious several years before the actual diagnosis of diabetes.

Cystic Fibrosis-Related Diabetes with strict glycaemic control is not associated with frequent intravenous antibiotics use for pulmonary infections

AimsPulmonary infections are more frequent in and associated with higher mortality in Cystic Fibrosis-Related Diabetes (CFRD) patients compared to CF patients without CFRD. Hyperglycaemia can lead to a higher vulnerability for infections. Aim of the study was to test whether the infection rate in well-controlled CFRD patients was similar to that in CF patients without CFRD. MethodsThis is a retrospective six-year cohort analysis on a consecutive series of 138 CF patients. They were categorized in two groups with CFRD or without CFRD. Pulmonary infection frequency was defined as the number of intravenous (IV) antibiotic treatments. Clinical factors associated with infection frequency were collected. ResultsCFRD was diagnosed in 54 (39%) CF patients of whom 44 (81%) achieved target value for glycaemic control (HbA1c 7.0% (⩽53mmol/mol)). Median frequency of IV antibiotics was 0 without CFRD and 3 episodes in patients with CFRD (rate ratio (RR) 2.9 (95% CI 1.6–5.2)). Multivariate analysis showed that frequency of IV antibiotics was significantly related to Pseudomonas aeruginosa colonization (RR 3.7) and lower lung function at baseline (RR 0.97) but not to CFRD by itself. ConclusionsIn this cohort with overall strict glycaemic control, the frequency of IV antibiotics use was related to chronic infection and impaired lung function at baseline, but not to CFRD by itself. Although this study in itself does not prove beneficial effect of strict glycaemic control, it does emphasize the potential role of glycaemic control on infection frequency in CF patients.

Staphylococcus aureus and Pseudomonas aeruginosa co-infection is associated with cystic fibrosis-related diabetes and poor clinical outcomes.

Cystic fibrosis-related diabetes (CFRD) patients suffer from accelerated rates of pulmonary decline compared to cystic fibrosis (CF) patients with normal glucose tolerance (NGT). However, the mechanisms underlying this difference are unknown. While CFRD is associated with increased respiratory infections, a link between infection and enhanced pulmonary dysfunction remains unclear. The development of glucose intolerance is spectral, resulting in impaired glucose tolerance (IGT) prior to the diagnosis of CFRD. Inclusion of IGT patients within the NGT group may diminish the ability to identify correlations with CFRD. With this in mind, this study aimed to determine if the association between CFRD and respiratory infections is correlated with pulmonary decline. Respiratory cultures from 234 CF patients with confirmed diagnosis of NGT or CFRD were analyzed to measure rates of infection, focusing on the two most prevalent bacteria in CF, Staphylococcus aureus and Pseudomonas aeruginosa. Infection status was correlated with pulmonary function and confounding clinical variables including age, gender, blood glucose levels, and CF transmembrane conductance regulator (CFTR) phenotype were considered in multivariate analyses. CFRD patients, particularly those with extremely high blood glucose levels, were more likely than NGT patients to be co-infected with S. aureus and P. aeruginosa, compared to infection with only one pathogen. Co-infection was associated with decreased lung function and increased frequency of pulmonary exacerbations, even after adjustment for confounding variables. Alterations in the microbial community composition, as opposed to the presence of a single pathogen, may account for greater pulmonary decline in CFRD patients.

Advanced glycation end products are elevated in cystic fibrosis-related diabetes and correlate with worse lung function

BackgroundThe onset of cystic fibrosis-related diabetes (CFRD) exacerbates lung function decline and increases mortality. One pathway that may worsen the lung dysfunction associated with CFRD is that of the receptor for advanced glycation end products (RAGE) and its ligands. MethodsHuman plasma was obtained from age-matched healthy, CF and CFRD patients. Plasma RAGE ligands (i.e. advanced glycation end products, S100A12, and high-mobility group protein B1) and soluble RAGE (sRAGE) levels were measured. ResultsCFRD patients had elevated plasma levels of AGEs and S100A12. Soluble RAGE, a RAGE ligand decoy receptor, was not significantly different between groups. Plasma AGE levels and S100A12 levels had significantly negative correlations with FEV1. ConclusionsAGEs are significantly elevated in CFRD and correlate negatively with FEV1. CFRD patients did not have significant increases in the decoy sRAGE, suggesting there may be heightened binding and activation of RAGE in CFRD exacerbating activation of proinflammatory pathways.

Diabetic retinopathy in patients who do not meet the diagnostic criteria for cystic fibrosis related diabetes

The UK Cystic Fibrosis (CF) Trust guidelines state that the diagnosis of CF related diabetes (CFRD) should only be made after an oral glucose tolerance test in the diabetic range and hyperglycaemia on serial monitoring. We report three patients with CF who were known to have abnormal glucose tolerance but did not meet the diagnostic criteria for CFRD. As the patients were commenced on insulin they were referred for annual diabetic complication screening and all were diagnosed with diabetic retinopathy. As these patients developed complications without being diagnosed with the causative disease, it questions the current diagnostic criteria for CFRD. This patient group also disproves the hypothesis that CFRD patients without fasting hyperglycaemia do not develop microvascular complications and suggests that, in some patients, such complications may develop earlier than previously thought. Copyright © 2015 John Wiley & Sons.

174 Frequency of diabetic keto-acidosis in children with cystic fibrosis related diabetes

Objectives To evaluate the frequency of diabetic keto-acidosis (DKA) in cystic fibrosis related diabetes (CFRD) population and to identify associated risk factors. Methods A retrospective database review of all CF patients with diabetes mellitus (DM) from 1992 to 2014. Data collected included demographics, sweat chloride, sputum culture, evidence of compliance, DM diagnosis parameters, insulin dose and weight profile prior to the diagnosis of DM. CFRD was diagnosed as per American Diabetes Association guidelines. Results Of 392 children with CF, 47 (12%) had DM: CFRD (n = 44), type 1(n = 2, 1 had DKA) and type 2 (n = 1). Only 2/44 patients with CFRD had DKA. Each patient had evidence of poor compliance with CF and DM managements and presented with pulmonary exacerbation and DKA. Both patients had higher HbA1c and insulin dose when compared to the CFRD group (Table). Pseudomonas (56%) and Aspergillus (23%) isolation was higher in CFRD patients when compared to non-CFRD patients. 47% CFRD patients had significant weight loss in 3 months preceding diagnosis – mean 7.4% (range 2–22). TableComparison of the 2 DKA patients with CFRD groupData are expressed as mean(SD) (range).CFRD group (n = 42)CFRD DKA Case 1CFRD DKA Case 2Age at CFRD diagnosis (years)13.8(2) (10–17)1311Sweat Chloride (mmol/L)107(17) (74–165)10385OGTT results (mmol/L) at 0 hrs6.4(2.5) (4–17)Presented in DKA6.5 at 2 hrs12.5(4.8) (4–26)11.8Pulmonary exacerbation at diagnosisNoneYesYesHbA1c (%)7.1(2.5) (5–16.8)10.614Insulin dose (IU/kg/day)0.6(0.8) (0–2.2)3.83.4Number of episodes of DKA03 in total, 1st at diagnosis2 since diagnosisFactors associatedN/APoor compliance high insulin dose & HbA1c (both) Conclusion DKA in CFRD is uncommon (5%) when reviewed over 22 years. Poor compliance with CF therapy and poor diabetic control (high insulin dosage and HbA1c) were common factors. An index of suspicion for keto-acidosis is indicated when those patients present with pulmonary exacerbations. Oral glucose tolerance test is indicated in patients with persistent weight loss and/or new sputum microbiology.

EPS06.1 Stenotrophomonas maltophilia is increased in patients with cystic fibrosis-related diabetes and displays enhanced growth under physiologically-relevant levels of glucose

The CF lung facilitates the cohabitation of diverse microbial organisms. These communities diversify as a result of interactions with both the environment and each other. Cystic fibrosis-related diabetes (CFRD) is an increasingly recognised and complex issue in the management of CF patients. There has been little research into the effect that this change in the host has on the associated microbiome. Objectives The main objective of this study was to determine the bacterial community structure in patients with CFRD. Methods and Results Clinically significant dysglycemia was confirmed using continuous glucose monitoring showing interstitial glucose readings of 7.8 mmol/L for more than 4.5% of the time. Amplicon-sequencing using Illumina Miseq of the 16S rRNA gene was performed on DNA extracted from sputum samples taken during outpatient visits. Analysis was performed using uSearch/Qiime pipeline and R package. Sequencing of 19 diabetic and 22 non-diabetic patients revealed a diverse microbial population. In CFRD patients, a significantly higher level of S. maltophilia was detected and confirmed using qPCR. In vitro studies were performed using physiologically relevant levels of glucose (0–10 µM). S. maltophilia displays a significant increase in growth in glucose rich environments suggesting that this bacterium is adept at exploiting this niche. The importance of glucose control in CFRD cannot be underestimated as it has potential to predispose the growth of resistant organisms. Increased understanding of these complex interactions between the microbiome and host may ultimately lead to altered CF patient management. We acknowledge the Leverhulme Trust for funding.

176 Elevation of 90 minutes plasma glucose during oral glucose tolerance testing predicts development of cystic fibrosis related diabetes and lung function decline

Objectives Recent studies have shown the effect of cystic fibrosis related diabetes (CFRD) on nutritional status and lung function of patients with CF. The aim of our study was to determine the prevalence of CFRD in Slovenian children with CF and the influence of hyperglycemia on their lung function and nutritional status. Methods Data from all Slovenian children with CF were collected. A diagnosis of CFRD was made based on oral glucose tolerance testing (OGTT) and continuous glucose monitoring. The highest level of blood glucose (BG) and the time during the OGTT were evaluated. Nutritional status and lung function of patients with CFRD were determined and compared to CF patients without CFRD. Results A total of 70 patients with a median age of 10.97 (0.9–22.3) years are managed in our Center. Twelve were diagnosed with CFRD (10 girls and 2 boys; median age 15.97 (9.21–18.59) years. The prevalence of CFRD was 17.1%. In 9 the BG levels >11.1 mmol/l at 90 ; during the OGTT were observed. The median value ob glycosylated hemoglobin (HbA1c) at diagnosis was 6.15 (5.6–6.8)%. The median FEV1 was 62% of predicted value and BMI 18.2 (12.4–21.7) kg/m 2 which is the 21 st percentile for age and gender. In patients with CFRD the median FEV1 was 24% lower compared with the rest of our CF patients while there was no significant difference in their BMI. Conclusions The prevalence of CFRD in our Center is comparable to the published data of CF patients of the same age group. Most of the CFRD patients had the highest BG level at 90 ; during OGTT. CFRD was associated with decline in lung function while it had no significant impact on nutritional status of our patients.

Diabetes-related Mortality in Adults with Cystic Fibrosis. Role of Genotype and Sex

Diabetes is associated with increased mortality in cystic fibrosis. Aggressive screening and early institution of insulin treatment significantly reduced this risk over the period of 1992-2008. To determine if progressive improvement in cystic fibrosis-related diabetes (CFRD) mortality has continued since 2008, and examine associations with CFTR genotypes linked to pancreatic insufficiency and to sex. Chart review was performed on 664 patients followed from 2008 to 2012. Overall mortality for patients with CFRD was 1.8 per 100 person-years, compared with 0.5 in patients with CF without diabetes (P = 0.0002); neither rate changed significantly from mortality reported for 2003-2008. Genotype impacted both mortality and diabetes risk: adults with severe CFTR genotypes experienced greater mortality at every age older than 32 years than those with mild genotypes (P = 0.002), and the risk of developing CFRD was also greatly increased in those with severe genotypes (prevalence 60% in adult patients with severe vs. 14% in adults with mild mutations). CFRD had a direct influence on mortality because it was associated with increased risk of death within each genotype category (20 vs. 2%, P = 0.007 for mild; 12 vs. 4%, P = 0.012 for severe). There was also a sex difference in adults with severe CFTR genotypes; both mortality and CFRD prevalence were higher at every age in females than males. Despite substantial improvement over time, mortality for CFRD patients greater than 30 years remains higher than for patients with CF without diabetes.

Use of Dipeptidyl Peptidase-4 Inhibitors in a Subset of Patients with Cystic Fibrosis Related Diabetes

Cystic Fibrosis Related Diabetes (CFRD) is the most common comorbidity in patients with Cystic Fibrosis (CF) and its incidence is rising. CFRD is associated with a decline in clinical status and six-fold increased mortality in patients with CF, the outcomes of which can be improved with early diagnosis and proper treatment. While current treatment guidelines recommend the use of insulin monotherapy to treat CFRD and do not recommend oral agents, these guidelines were published before the use of dipeptidyl peptidase-4 inhibitors (DPP-4). We present two cases of CFRD patients who were successfully managed with DPP-4 inhibitors both inpatient as well as outpatient.