285 The use of dipeptidyl peptidase-4 inhibitors (DPP-4) in CF-related diabetes (CFRD)

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detected with CFLBMD did not require any specific treatments. Although guidelines recommended early and regular DEXA scans, this study showed that routine assessment in all CF adolescents may not be necessary or useful. Limiting its use to those with associated risk factors as well as the reduction of risk factors for CFLRMD may be more appropriate in the adolescent years. 282 Dental care and hygiene in adults with cystic fibrosis on bisphosphonate therapy attending the All Wales Adult CF Centre (AWACFC) A. Wilby1, H. James2, L. Speight1, H. Jarvis1, D. Lau1, R.I. Ketchell1, J. Duckers1. 1 University Hospital Llandough, All Wales Adult CF Centre, Penarth, United Kingdom; 2Cardiff University, School of Medicine, Cardiff, United Kingdom Background: CF related low bone mineral density (CFRLBMD) occurs in 20 percent of patients. CFRLBMD is commonly treated with bisphosphonates, which carry a risk of jaw osteonecrosis (BONJ). Patients with cystic fibrosis commonly have poor oral hygiene due to use of inhaled corticosteroids and consumption of a high sugar diet. Dental extraction and poor oral health further increase the risk of BONJ**. The British National Formulary (BNF) advises that patients should see a dentist prior to and during bisphosphonate therapy to improve dental hygiene. Aim: To ascertain how many adult patients attending the All Wales Adult CF Centre (AWACFC) saw a dentist prior to commencing bisphosphonate treatment and their self reported dental record. Method: Dental questionnaires were distributed over a six week period to patients on bisphosphonate therapy attending outpatient clinics at the AWACFC. Results: 19 questionnaires were returned (64% response rate). 68% did not see a dentist before starting bisphosphonates and of those who did see a dentist 79% had not discussed with their dentist the importance of good oral hygiene whilst taking bisphosphonates. 53% of patients had at least one filling, 53% had at least one tooth removed and 16% had a dental crown placement. 53% had never seen a dental practice hygienist. Conclusion: Over two thirds of the patients surveyed had not seen a dentist before commencing bisphosphonate therapy therefore not complying with the BNF recommendation. Over half had at least one tooth removed and over a half had never seen a dental hygienist and therefore further increasing the potential risk of BONJ. Healthcare professionals should recommend good dental hygiene practices for patients on bisphosphonates and encourage them to register with a dental practice. 283 Cystic fibrosis-related diabetes screening: are there easy measures to implement the guidelines? V. Terlizzi1, L. Lenzi2, I. Fusco1, L. Biagi1, A. Ingicco1, C. Braggion1. 1Tuscany Regional Cystic Fibrosis Centre, Meyer University Children’s Hospital, Florence, Italy; 2Tuscany Regional Centre of Pediatric Diabetes, Meyer University Children’s Hospital, Florence, Italy Objectives: The Cystic Fibrosis (CF) Foundation CFRD guidelines recommend screening to all individuals annually, starting at age 10, with an oral glucose tolerance test (OGTT). Nevertheless in 2015 the median percentage of non-diabetic individuals receiving OGTT is 29,1% in American patients with more than 18 years and 57,2% in patients with 10 to 17 years. We report the rates of the screening for CFRD using the OGTT in CF Center of Florence (Italy) in the years 2010–2015 and the measures taken to implement CFRD guidelines. Methods: The standard OGTT ( patient fasted for 8 hours, 1.75 g/kg body weight oral glucose up to a maximum of 75 g, 2-h test) was planned in individuals with more than 10 years. In the years 2010–2012 we obtained a fasting and after 2 hours blood sample by venipuncture, while in the range 2013–2015 the blood was drawn by capillary puncture of fingertip in order to make the exam easier and tested by plasma-calibrated glucometer. Furthermore in the range 2013–2015 we included the OGTT as a procedure to be performed at the annual general control in all non-diabetic individuals. We compared the rates of screening for CFRD in the two

three-year periods. We defined OGTT as pathological in presence of CFRD or Impaired Glucose Tolerance (IGT). Results: in 2010–2012 the OGTT was carried out by 25.6–26.8% of individuals [2010: 40/149 (26,8%), pathological in 5/40 (12,5%); 2011: 43/ 168 (25,6%), pathological in 6/43 (13,9%); 2012: 41/156 (26,3%), pathological in 5/41 (12,1%)]. In 2013–2015 the percentage was 46,9–53% [2013: 77/166 (46,4%), pathological in 17/77 (22%); 2014: 84/165 (50,9%), pathological in 22/84 (26%); 2015: 96/181 (53%), pathological in 25/96 (26%)]. Conclusions: The adopted measures to implement the CFRD diagnosis guideline led to an increase in the number of OGTT practiced and diagnosis carried in our center. A guideline must provide advice and tools on how the recommendations can be put into practice in order to improve the applicability. 284 Experiences with a novel pancreatic enzyme medication in Europe tested in a Scandinavian CF-center M. Nilsson1, C.R. Hansen1. 1Skåne University Hospital, Childrens Hospital, Lund, Sweden Objectives: To test a enteric-coated, bicarbonate-buffered pancreatic enzyme (Pertzye®) to children with cystic fibrosis, since many patients need proton pump inhibitor (PPI) in combination with pancreatic enzyme therapy (PERT). Methods: Children with verified cystic fibrosis mutations and pancreatic insufficiency with positive fecal elastase-1 that not had a satisfied weight for height and/or gastrointestinal symptoms (GI) that did not have a satisfying result with Creon®. All patients had PERT with Creon® since this was the only avalable PERT in Sweden. GI-symptoms and BMI z-score were selected as parameters. Results: Total of eight children (6 girls and 2 boys), and median age of 9,7 (5,2–17,8) when started on Pertzye. Five was on PPI in combination with Creon. The starting dose was 80% of Creon-dose and then titrated to the best GI result. Three did not want to continue because of abdominal pain. The other five have a lower dose of lipase than the former dose of Creon, 54,400 lipase vs 65,000 lipase per mainmeal (16%). BMI z-score was almost the same after one year with Pertzye (−0,79 vs −0,88). Conclusion: It was a very small study with only eight patients of total 62 children at the center. Three children could not continue beacuse of abdominal pain, two boys and one girl, but five children had fewer gastrointestinal symtoms with a lower dose. BMI z-score was the same after one year treatment. Pertzye could be worth testing on patients with very high dosis of Creon and/or have GI symptoms not solved with Creon. 285 The use of dipeptidyl peptidase-4 inhibitors (DPP-4) in CF-related diabetes (CFRD) H. Sunsoa1, J. Barrett1, C. Roden1, T. Osborne1, E. Glennon1, R. Rashid1, J.L. Whitehouse1, E.F. Nash1. 1West Midlands Adult CF Centre, Birmingham, United Kingdom Introduction: Treatment of CF-related diabetes (CFRD) typically involves the use of subcutaneous insulin, however in a proportion of patients alternative approaches are considered. Dipeptidyl peptidase-4 (DPP-4) inhibitors are generally used in people with type 2 diabetes, either alone or in combination with insulin. Little is known about the efficacy of DPP-4s in CFRD. The aim of this study was therefore to explore the efficacy of DPP-4s (without concomitant insulin) in our large regional adult CF centre. Methods: We analysed the following parameters in patients receiving DPP4s from 2013 to 2016 before and after receiving treatment: FEV1, weight, BMI, 7-day CGMS & HbA1C. Results: 400 patients were attending our centre during the study period, with 208 (52%) having CFRD. 30 patients received a DPP-4: 17 patients received DPP-4 with insulin, 13 patients received DPP-4 alone (9 male, mean age 31 yrs, 7 F508del homozygous,100% pancreatic insufficient). Rationale for DPP-4 included: CFRD (n = 5), abnormal blood glucose/ impaired glucose tolerance (n = 8). 11 patients received Sitagliptin 100 mgs daily, 2 received Linagliptin 5 mgs daily. Comparing pre vs. post-DPP-4 values, time spent with glucose above 8 mmol/L on CGMS decreased from

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18.2 (7–27)% (median (IQR) to 10.2 (2–16)% ( p = 0.03) and HbA1C decreased from 45 (41–46) mmol/mol to 41 (38–45) mmol/mol ( p = 0.01). FEV1 and BMI did not significantly change. There were no significant side effects. Conclusion: This study demonstrates that DPP-4s can be effective in improving glycaemic control in CFRD. Benefits include: a single daily tablet, minimal risk of hypoglycaemia, reduced monitoring of blood glucose levels and no impact on weight. Sitagliptin is metabolism by the liver, so is generally avoided in patients with significant CF liver disease but Linagliptin is considered safe in these patients. In our experience, DPP-4s are particularly useful in patients with moderate glucose excursions (>8 mmol/L) and with barriers to insulin treatment. 286 Evaluation of HbA1c and OGTT-results after a first abnormal OGTT D. Declercq1, S. Van Daele1, F. De Baets1, S. Van Aken1, S. Van Biervliet1. 1 Ghent University Hospital, Gent, Belgium Objectives: CFRD is a life threatening comorbidity and increases with age. Because of fluctuating glycemic response in CF, there is still debate on the screening method and cutoff for treatment initiation. Methods: From 182 patients followed at the Ghent CF Centre OGTT and HbA1c results between 2006 and 2016 were retrospectively analysed. An OGTT is performed annually in all clinical stable CF patients above 10 years of age. HbA1c is measured at the same time. Results are given as median and quartiles between brackets. Results: 67 patients (67 EPI; 35 male) with an abnormal OGTT at 2 h (>140 mg/dL) had a median age 16,9 years (12,5; 25,4). Insulin therapy was started when the patient had typical clinical symptoms and/or adverse effects of hyperglycemia. Only 14 (20.8%) patients started insulin therapy, of which 7 had a 2 h glycemia >2 g/L, however, a delay of 0,6 y (0,01; 3) after a first abnormal OGTT was observed. Of the remaining 53 untreated patients, 8 had a 2h-glycemia >2 g/L (B) (median glycemia 2,21 g/L (2,05; 2,49), HbA1c 5,7% (5,5; 5,7). The remaining 45 patients (2h-glycemia 1,4– 2 g/L (A)) (24 male) had a median 2h-glycemia 1,6 g/L (1,47; 1,72), HbA1c 5,7% (5,5; 5,8). No statistical significant difference was found for the repeated OGTT and HbA1c measurements. In Table 1 annual follow-up is presented. Conclusion: Over a 5 year follow-up a slight increase in number of patients with an Hba1c>6% is seen independently of the OGTT result. A further in depth study adding CGM is ongoing. 287 Lactase activity in small intestinal biopsies in cystic fibrosis (CF) children E. Roslavtseva1, O.I. Simonova1, M. Lokhmatov1, A. Tupylenko1, A. Ignatova1, Y. Gorinova1. 1Scientific Center for Children’s Health, Moscow, Russian Federation Objectives: Dyspeptic symptoms are frequent in CF children with exocrine pancreatic insufficiency despite optimal pancreatic substitution. Our aim was to determine the frequency of lactase deficiency and its possible association with clinical and endoscopic symptoms in children with CF. Methods: In 31 children with CF, severe pancreatic insufficiency (elastase1 < 50) aged 11 months – 14 years, not limited to dairy products, lactase

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activity was determined by semiquantitative «Lactose Intolerance quick test» by «Biohit Oyj», Finland, in biopsies of jejunum mucosa obtained during gastroscopy. The test is based on the ability of the bioptate to break down lactose to glucose and galactose. Assessment of results is made through a 20-minute comparison of the color reaction. Results: Reduction of lactase activity in the intestinal biopsies was detected in 14 of 31 (45.2%) children: severe in 9 (29%), moderate in 5 (16.1%) cases. However, we did not get the correlation (r < ± 0,3) between lactase activity and endoscopic changes in the esophagus, stomach, duodenum and jejunum, and the frequency of diarrhea, abdominal pain and bloating. There were no significant differences in the nutritional status (BAZ, WHO AnthroPlus) of children with normal lactase activity and hypolactasia. Conclusion: The data on the frequency of lactase deficiency in CF differ significantly [1,2]. Low lactase activity in the biopsies were detected more frequently than in the age-old study [1], but the clinical significance of this fact was undefined. Taking into account the data on the significance of intestinal inflammation in the genesis of malabsorption in CF [3], it requires further study comparing the diagnostic value of different methods of lactase deficiency diagnosis.

References [1] Antonowicz I, Reddy V, Khaw K-T, Schwachmann H. Pediartics 1968; 42 (3): 492–500. [2] Modiano G, Ciminelli B, Pignatti PE. Eur J Human Genetics 2007; 15: 225–93. [3] Gonska T. J Pediatr Gastroenterol Nutr 2016; 62 (4): 518–9. 288 Losartan-associated sprue-like enteropathy in a post-lung transplant cystic fibrosis patient A.P. Sawant1, G. Spoletini1, C. Etherington1, A.C. Ford2, P. Whitaker1, I. Clifton1, D. Peckham1,2. 1The Leeds Regional Adult Cystic Fibrosis Centre, St James’s University Hospital, Leeds, United Kingdom; 2Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom Background: Drug-induced enteropathy is a recognised cause of seronegative villous atrophy and has been described in patients receiving azathioprine, mycophenolate, and methotrexate. More recently, oral angiotensin-2-receptor blockers, such as olmesartan and irbesartan have been implicated. We report a case of losartan-induced villous atrophy in a post double lung transplant patient with cystic fibrosis (CF). Case presentation: A 42 year-old man with a history of CF, pancreatic insufficiency, double lung transplant and hypertension presented with a two month history of persistent abdominal pain, bloating, watery stools and weight loss. Initial investigations included abdominal x-ray, computed tomography, stool microscopy and culture and coeliac serology. As all the results proved negative, an upper endoscopy with distal duodenal biopsies was undertaken. Histology revealed partial villous atrophy consistent with a drug-induced enteropathy. On discontinuation of losartan his symptoms rapidly disappeared and repeat biopsy showed histological improvement. Conclusion: Oral angiotensin-2-receptor antagonists can be associated with a reversible sprue-like enteropathy. Although this is relatively rare, identifying the correct diagnosis remains essential as discontinuation of the responsible drug results in dramatic clinical and histological improvement.

Table 1: (abstract: 286) Annual follow-up after first abnormal OGTT Cutoff (g/L) A:1,4– 2; B: >2; Total n <1,4 g/L 1,4–2 g/L >2 g/L HbA1c <5,5% 5,5–6% >6%

OGTT;T0 n = 45; n = 8; n = 53 0; 0 45(100%); 0 0; 8(100%) n = 45; n = 8; n = 53 12(27%); 0 30(67%); 8(100%) 3(6%); 0

OGTT;T + 1 yr n = 40; n = 5; n = 45

OGTT;T + 2 yr n = 38; n = 4; n = 42

OGTT;T + 3 yr n = 31; n = 2; n = 33

OGTT;T + 4 yr n = 24; n = 3; n = 27

OGTT;T + 5 yr n = 21; n = 2; n = 23

26(65%); 2(40%) 8(20%); 3(60%) 6(15%); 0 n = 42; n = 5; n = 47

25(66%); 2(50%) 11(29%); 2(50%) 2(5%); 0 n = 39; n = 3; n = 42

22(71%); 0 5(16%); 1(50%) 4(13%); 1(50%) n = 32; n = 3; n = 35

15(63%); 2(67%) 7(29%); 1(33%) 2(8%); 0 n = 27; n = 2; n = 29

9(43%); 0 6(28,5%); 2(100%) 6(28,5%); 0 n = 26; n = 3; n = 29

15(36%); 1(20%) 24(57%); 4(80%) 3(7%); 0

11(28%); 0 24(62%); 2(67%) 4(10%); 1(33%)

7(22%); 0 22(69%); 3(100%) 3(9%); 0

8(30%); 0 16(59%); 2(100%) 3(11%); 0

8(31%); 0 14(54%); 2(67%) 4(15%); 1(33%)