The Four-week Study of Skin Sites Used for Diabetes Devices in Children and Adolescents.

An increasing proportion of patients with diabetes mellitus type 1 (T1D) is using diabetes devices in order to achieve better glycemic control, improved quality of life and more flexible lifestyle (1-4). Continuos subcutaneous insulin infusion (CSII) or insulin pumps are infusing small doses of insulin by a catheter fastened to the skin by an infusion set. Modern systems with automated insulin delivery (AID) as the precursor to the completely automated artificial pancreas, give algorithm-based corrections on basis of the interstitial fluid glucose measurement from the continuos glucose monitor (CGM). The first studies on these new more automated closed loop systems show improvements in Time in Range (TIR) but still with room for improvement. (5). The absorption of insulin is a very important measure that potentially could vary a lot in relation to both age, sex, timing, exercise, blood flow and a whole range of other aspects, but especially also according to the tissue that insulin is infused into. The skin site used for the infusion set is therefore increasingly important, and this could therefore account for at least some of the glycemic variability seen even in patients using these highly automated systems.

Ultrasound have shown promising results to investigate the subcutaneous areas by means of both density and vascularity. Regarding the density of tissue, hyper- and hypo- echogenicity are important measures. An- other newly study have also shed light on the subcutis and the findings of lipohypertrophy or pre-clinical lipohypertrophy by ultrasound (6). A study from our team similarly found proportions of hyperechogenicity among 60%-75% of all insulin pump users, with as well neovascularization in about 10% of the users (7). The hyper echogenicity is an ultrasonic sign of increased density of the tissue, and whether this is inflammation, lipohypertrophy, or fibrosis is unknown, but since this is seen in most areas used for insulin pumps, the con- sequences of the unspecific increased tissue density on the absorption of insulin is highly relevant.

The risk factors for developing hyperechogenicity besides infusion of insulin is unknown, but the occurrence of eczema and subtle changes in dermis are suspected to be associated with an increased risk of subcutaneous reactions. The subtle nonvisible changes in the skin could be level of natural moisturizing factor (NMF), lipids, cytokines and microbiome. Simultaneously investigation of the skin barrier and subcutis have not been investigated previously, why investigating the interaction between the two is important.

To maximize the effect of insulin pumps, there is therefore a lack of knowledge on the skin sites, especially in means of the consequences of the subcutaneous changes as hyper-echogenicity and vascularization among insulin pump users.

4. Aim The primary aim of present study is therefore to investigate how insulin infusion in hyperechogenic areas of subcutis affects the effect of insulin on blood glucose.