Inger Hee Mathiesen1, Mette Friberg Hitz2, Terese Lea Katzenstein3, Peter Oturai4, Marianne Skov5, Niklas Rye Jørgensen6, Peter Oestrup Jensen7, Christine Raaberg Mikkelsen3, Rikke Krogh-Madsen8, Tacjana Pressler9, Daniel Faurholt-Jepsen3. 1. Copenhagen Cystic Fibrosis Center, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK2100 Copenhagen, Denmark. Electronic address: ihm@dadlnet.dk. 2. Dept. of Medicine, Endocrine Division, Zealand University Hospital, Lykkebaekvej 1, DK4600 Koege, Denmark. 3. Copenhagen Cystic Fibrosis Center, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK2100 Copenhagen, Denmark. 4. Dept. of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Blegdamsvej 9, Copenhagen University Hospital, DK2100 Copenhagen, Denmark. 5. Copenhagen Cystic Fibrosis Center, Danish Pediatric Pulmonary Service, Copenhagen University Hospital, Juliane Maries Vej 6, DK2100 Copenhagen, Denmark. 6. Dept of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Valdemar Hansens Vej 13, 2600 Glostrup, Copenhagen, Denmark. 7. Dept. of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital, Ole Maaløes Vej, 26, DK2200 Copenhagen, Denmark; Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK2100 Copenhagen, Denmark. 8. The Centre of Inflammation and Metabolism (CIM), Centre for Physical Activity Research (CFAS), Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK2100 Copenhagen, Denmark. 9. Copenhagen Cystic Fibrosis Center, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK2100 Copenhagen, Denmark; Copenhagen Cystic Fibrosis Center, Danish Pediatric Pulmonary Service, Copenhagen University Hospital, Juliane Maries Vej 6, DK2100 Copenhagen, Denmark.
Abstract
BACKGROUND: Cystic fibrosis(CF) related diabetes(CFRD) and osteoporosis are prevalent in adult patients with CF. We aimed to evaluate if CFRD and markers of glucose metabolism and inflammation are associated with bone turnover in CF. METHODS: Cross sectional study at the adult section at the Copenhagen CF Center from January-October 2017. Fasting blood samples, including bone turnover markers(BTMs) and cytokines, Dual-x-ray absorptiometry scan and oral glucose tolerance test were performed. Lung-transplanted participants and patients in antiosteoporotic treatment were excluded from analyses. RESULTS: 102 patients were included of whom 19 had a prior CFRD diagnosis. CFRD patients had lower procollagen type 1 N-terminal propeptide(P1NP) and C-Terminal cross-linked Telopeptide(CTX) levels compared to CF patients without diabetes (median[IQR]) 49.5 μg/l [29.6,57.1] vs 56.9 μg/l [38.2,74.3], p = .03 and 0.2 μg/l [0.1,0.3] vs 0.4 μg/l [0.3,0.6], p < .01, respectively. Fasting plasma glucose(FPG) was negatively associated with the bone formation markers P1NP and osteocalcin and bone resorption marker CTX. In multivariate linear regression FPG remained a significant predictor of P1NP -1.07 [-1.09;-0.01] and CTX -1.13 [-1.21;-1.06]. Bone mineral density Z-score was not different between patients with and without CFRD but FPG was negatively associated with hip and femoral neck Z-score. There was no consistent association between inflammatory cytokines and BTMs. CONCLUSIONS: Bone turnover markers are reduced in CF patients with CFRD and negatively associated with glucose levels. Extra attention towards frequent hyperglycemia in CF patients should be taken when evaluating decreased BMD. Glycemia may be a future target for improving outcome in CFBD.
BACKGROUND:Cystic fibrosis(CF) related diabetes(CFRD) and osteoporosis are prevalent in adult patients with CF. We aimed to evaluate if CFRD and markers of glucose metabolism and inflammation are associated with bone turnover in CF. METHODS: Cross sectional study at the adult section at the Copenhagen CF Center from January-October 2017. Fasting blood samples, including bone turnover markers(BTMs) and cytokines, Dual-x-ray absorptiometry scan and oral glucose tolerance test were performed. Lung-transplanted participants and patients in antiosteoporotic treatment were excluded from analyses. RESULTS: 102 patients were included of whom 19 had a prior CFRD diagnosis. CFRD patients had lower procollagen type 1 N-terminal propeptide(P1NP) and C-Terminal cross-linked Telopeptide(CTX) levels compared to CFpatients without diabetes (median[IQR]) 49.5 μg/l [29.6,57.1] vs 56.9 μg/l [38.2,74.3], p = .03 and 0.2 μg/l [0.1,0.3] vs 0.4 μg/l [0.3,0.6], p < .01, respectively. Fasting plasma glucose(FPG) was negatively associated with the bone formation markers P1NP and osteocalcin and bone resorption marker CTX. In multivariate linear regression FPG remained a significant predictor of P1NP -1.07 [-1.09;-0.01] and CTX -1.13 [-1.21;-1.06]. Bone mineral density Z-score was not different between patients with and without CFRD but FPG was negatively associated with hip and femoral neck Z-score. There was no consistent association between inflammatory cytokines and BTMs. CONCLUSIONS: Bone turnover markers are reduced in CFpatients with CFRD and negatively associated with glucose levels. Extra attention towards frequent hyperglycemia in CFpatients should be taken when evaluating decreased BMD. Glycemia may be a future target for improving outcome in CFBD.