The DERMIS Study: Evaluation of Insulin Pump Infusion Sites in Type 1 Diabetes

Background: Continuous subcutaneous insulin infusion (CSII) for type 1 diabetes is increasing in use. Pump site failures are common, yet little is known about the skin changes from pump use. Using noninvasive optical coherence tomography (OCT), OCT angiography (OCTA), and skin biopsies, we evaluated the skin changes of chronic insulin infusion.Methods: OCT operating at 1310nm central wavelength with a bandwidth of 100 nm was performed immediately before skin punch biopsies were collected at three sites: a “current site”, a “recovery site” used 3 days prior to biopsy, and a “control” site never used for any insulin infusion or injection.Findings: OCT and OCTA identified characteristics of increased inflammation and vessel density at pump sites compared to control sites. Histological analysis of pump sites showed differences in skin architecture including fibrosis, inflammation including increased tissue eosinophils and fat necrosis. Immunohistochemical staining showed differences between infusion sites and the control sites for staining of insulin-like-growth factor-1 and transforming growth factor β-3.Interpretation: These findings support allergic sensitization as a potentially common reaction at CSII sites. The leading candidates include insulin preservatives, plastic materials, or adhesive glue used in device manufacturing. The inflammatory response caused by these common allergic responses may result in tissue changes responsible for the infusion site failures seen frequently in clinical practice.Funding: Funding was provided by the Leona M. and Harry B. Helmsley Charitable Trust.Declaration of Interests: AK, MMS, RW, JDB, XD, DK, JL and IBH report support for the present manuscript from Leona M. and Harry B. Helmsley Charitable Trust paid to their institution. RW reports grants from National Institutes of Health, Carl Zeiss Meditec Inc, Colgate-Palmolive Company and Estee Lauder Inc outside of the submitted work; consulting fees from Cyberdontics Inc, Carl Zeiss Meditec Inc outside of the submitted work; patents planned, issued or pending (US8,750,586, US8,180,134, US9,282,905, US9,759,544, US 10,354,378, US10,529,06) outside of the submitted work; and received equipment from Carl Zeiss Meditec Inc to his institution and a gift support from Washington Research Foundation to his institution outside of the submitted work. IBH reports grants and contracts from Insulet, Medtronic and Dexcom outside of the submitted work; consulting fees from Abbott Diabetes Care, Roche, Big Foot, Lifescan and Hagar outside of the submitted work; and honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Section editor: UpToDate outside of the submitted work.Ethics Approval: The University of Washington Human Subjects Division reviewed and approved the study. Because of the COVID-19 pandemic, minor modifications to the protocol became necessary, including remote visits for consenting and screening.