Background: CSII is used with increased frequency; however, there are no studies evaluating human skin histology related to its use. Objectives: 1) to investigate the skin histology and metabolite changes at CSII sites and 2) associate possible changes with clinical characteristics in a cohort of patients with T1D.

Methods: We conducted a cross-sectional study which included individuals with T1D using CSII. Skin and blood samples in addition to clinical data were collected. Histological, immunohistochemical (IHC) , and metabolomic analyses were performed using skin biopsies from three sites: 1) current 2) recent and 3) never used site (control) for CSII.

Results: A total of 30 participants were enrolled in the study (age 48.3 ± 17.9 years, female 66.7%, diabetes duration 30.4 ± 16.0 years, insulin pump use 15.7 ± 11.7 years, BMI 25.3 ± 3.4 kg/m2, HbA1c 6.66 ± 0.79%, mean glucose from CGM 150.7 ± 26.4 mg/dL, coefficient of variation 31.2 ± 4.4%, insulin dose 0.53 ± 0.17 IU/kg) . Histologic data showed a significant increase in inflammation, fibrin, fat necrosis, vascularity, eosinophils, and IHC staining of IGF-1 and TGFβ3 at both CSII sites compared to control sites (all p<0.001) . Targeted tissue analysis demonstrated an increase in critical metabolites at current sites compared to control, including histamine (p=0.013) , uracil (p<0.001) , and a trend in UDP-GlcNAc (p=0.063) . Inflammation is positively correlated with insulin dose (p=0.005) , in addition to mean glucose (p<0.01) and coefficient of variation (p<0.01) from the CGM.

Conclusion: Biologic changes were observed in skin histology and metabolites at CSII sites that may be associated with inflammation, oxidative stress response, protein synthesis and wound healing. These could have a clinical impact on insulin availability and diabetes control.


J. D. Baran: n/a. D. Khakpour: None. A. Kalus: None. M. Shinohara: Other Relationship; Aztex, Cabaletta Bio, Elorac. X. Dong: None. D. S. Hippe: Research Support; Canon America Medical Systems, GE Healthcare Systems, Philips Healthcare. I. B. Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic.


Leona M. and Harry B. Helmsley Charitable Trust

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