Advanced glycation end products are elevated in cystic fibrosis-related diabetes and correlate with worse lung function  William R. Hunt, Beth R. Helfman, Nael A. McCarty, Jason M. Hansen  Journal of Cystic Fibrosis  Volume 15, Issue 5, Pages 681-688 (September 2016) DOI: 10.1016/j.jcf.2015.12.011 Copyright © 2015 European Cystic Fibrosis Society Terms and Conditions

Fig. 1 Plasma levels for ligands to the receptor for advance glycation end products (RAGE). (A) Advanced glycation end products (AGEs) levels. AGEs were significantly elevated in CFRD compared to normoglycemic CF patients. There were no significant differences in AGE levels between healthy controls and CF patients. (B) S100A12 levels. Plasma S100A12 levels, also identified as extracellular newly identified RAGE-binding protein (enRAGE), were not significantly different between CFRD and CF groups. However, when compared to healthy controls, CFRD patients had significantly elevated plasma levels of S100A12. (C) High-mobility group protein B1 (HMGB-1) levels. There were significantly lower levels of plasma HMGB-1 in CFRD patients compared to CF, but there were no other differences between other groups. Boxes represent the 25th to 75th percentiles; median values are represented by the solid line within the box, whiskers represent the 10th and 90th percentile; and the single points represent outliers. *p<0.05. Journal of Cystic Fibrosis 2016 15, 681-688DOI: (10.1016/j.jcf.2015.12.011) Copyright © 2015 European Cystic Fibrosis Society Terms and Conditions

Fig. 2 Soluble receptor for advance glycation end products (sRAGE) levels. There were no significant differences in plasma levels of total sRAGE, a decoy receptor inhibiting intracellular RAGE signaling, between cohorts. Boxes represent the 25th to 75th percentiles; median values are represented by the solid line within the box, whiskers represent the 10th and 90th percentile; and the single points represent outliers. Journal of Cystic Fibrosis 2016 15, 681-688DOI: (10.1016/j.jcf.2015.12.011) Copyright © 2015 European Cystic Fibrosis Society Terms and Conditions

Fig. 3 Correlations with percent predicted forced expiratory volume in one second (FEV1%). Nonlinear regressions with FEV1 (%) as the dependent variable compared to clinical data and receptor of advanced glycation end products (RAGE) ligands. The range of FEV1 (%) is expressed as a fraction of 1. Graphs represent correlations between FEV1 (%) and (A) hemoglobin A1c percent (HgbA1c), (B) subject age (in years), (C) body mass index (BMI), (D) plasma advance glycation end product (AGE) levels, (E) plasma S100A12 levels and (F) total plasma soluble RAGE (sRAGE) levels. An individual dot represents a single subject; normoglycemic CF subjects are represented by black dots and CFRD subjects are represented by cyan dots; the black line represents the line of best fit; the blue lines represent the 95% confidence band; and the red lines represent the 95% prediction band. r=correlation coefficient. Journal of Cystic Fibrosis 2016 15, 681-688DOI: (10.1016/j.jcf.2015.12.011) Copyright © 2015 European Cystic Fibrosis Society Terms and Conditions

Fig. 4 Correlations with hemoglobin A1c (HgbA1c). Nonlinear regressions with HgbA1c as the dependent variable compared to systemic levels of receptor of advanced glycation end products (RAGE) ligands. Graphs represent correlations between HgbA1c and: (A) plasma advance glycation end product (AGE) levels, (B) total plasma soluble RAGE (sRAGE) levels and (C) plasma S100A12 levels. An individual dot represents a single subject; normoglycemic CF subjects are represented by black dots and CFRD subjects are represented by cyan dots; the black line represents the line of best fit; the blue lines represent the 95% confidence band; and the red lines represent the 95% prediction band. r=correlation coefficient. Journal of Cystic Fibrosis 2016 15, 681-688DOI: (10.1016/j.jcf.2015.12.011) Copyright © 2015 European Cystic Fibrosis Society Terms and Conditions