Individuals aged 16 years and older with T1D were approached and invited to fill out a questionnaire about device preferences anonymously. One group of patients was approached by providing study information and a link to the questionnaire on various Dutch online platforms for patients with type 1 diabetes: Dutch Diabetes Research Foundation, Dutch Diabetes Association, Juvenile Diabetes Research Foundation (JDRF) Netherlands, Dutch Diabetes Meeting Point, diabetestype1.nl and Regenerative Medicine Crossing Borders (RegMedXB). Parents of children diagnosed with T1D younger than 16 years were also invited to participate. A second group of patients who had visited the diabetes outpatient clinic at the Leiden University Medical Center (LUMC) in the Netherlands during the past 2 years, were contacted by e-mail and invited to participate with a link to the online questionnaire.

We developed a web-based questionnaire (Qualtrics, Supplementary Appendix SA) for self-reported background information (age, sex, time since diagnosis T1D, most recent time in range (TIR), most recent hemoglobin A1c (HbA1c), current treatment and current treatment center) and preferences regarding specific aspects of islet delivery devices and implantation strategies. These preferences comprised implant sites and device characteristics such as the number of devices, the dimensions and the minimal duration of function. Respondents were invited to add explanatory remarks to their answers. Explanatory remarks were coded into categories and validated by a second investigator. The second group of patients from the LUMC were also requested to complete the 20-item Problem Areas In Diabetes (PAID) questionnaire [12]. The anonymous data were collected from October 2021 until May 2022.

Incomplete questionnaires were excluded from data analysis. A single respondent who indicated sex to be other was excluded from univariate and multivariate analysis by sex. Age categories were pre-specified in the questionnaire (16–30, 31–50, 51–70, >70 years, or parent/caregiver). PAID scores were categorized as low (0–16), moderate (17–39) or high (40–100) diabetes distress [13]. HbA1c levels were reported in mmol/mol Hb and if necessary converted from a percentage by the formula “mmol/mol Hb = (10.93 × %)–23.5”. Data were analyzed in RStudio (version 2023.03.1) and GraphPad Prism (version 9.3.1) with α = 0.05. Multivariate multinomial logistic regression was performed on variables with categorical outcomes, for all respondents with covariates age, sex, HbA1c and method of recruitment and just for the respondents of the diabetes outpatient clinic with age, sex, HbA1c and categorized PAID score. The most selected answers for the outcomes preferred maximal size and minimal functional duration were selected as reference. Comparison of continuous outcomes in multiple groups was done by repeated measures one-way ANOVA with Geisser-Greenhouse correction and Tukey’s multiple comparison test. Univariate analyses of binary outcome were performed with chi-square test.

The online questionnaire was completed by 856 respondents (Supplementary Figure S1). The response rate was 43.1% amongst the approached patients of the LUMC diabetes outpatient clinic (412 respondents). Baseline characteristics of all respondents are presented in Table 1. The majority of respondents identified as female (58.1%) and were between the ages of 31 and 70 (71.8%). Forty-four percent of respondents had diabetes for more than 25 years. Mean self-reported HbA1c was 56.4 ± 12.4 mmol/mol Hb (N = 660) and mean self-reported TIR was 68.3% ± 17.3% (N = 465). The group of 412 patients also filled out the PAID questionnaire. The median PAID score was 25 (IQR: 12.5–39.1). Diabetes distress was determined to be low (PAID score 0–16) in 34%, moderate (PAID score 17–39) in 41% and high (PAID score 40–100) in 25% of respondents. Respondents recruited online were more often female, younger, had a shorter disease duration, and higher TIR than the patients contacted via the LUMC diabetes outpatient clinic (Supplementary Table S1).

Nearly all (97%) respondents would like to receive an IDD (Table 2). Some respondents were willing to already take part in safety studies (44.0%), others would only accept the IDD after the completion of safety studies (44.4%).

To explore the preferred maximal size of an implant, we surveyed 5 options (Table 3). We informed the respondents that a device would be flexible with a thickness of a credit card, and that it could be implanted, via a small incision, under the skin under local anesthesia at a location that would not be directly visible. Respondents were also informed that it could leave a scar. Most respondents (37.7%) preferred a maximal size corresponding to a FreeStyle Libre 2 sensor (diameter 3.5 cm), while 30.4% indicated that size was irrelevant. After correcting for sex, method of recruitment and HbA1c, respondents age >30 years compared to age 16–30 years were more likely to select a device with dimensions of a 2 Euro coin (diameter 2.6 cm) rather than a FreeStyle Libre 2 sensor (p-values 0.007–0.048). Furthermore, parents/caregivers were less likely to opt for the choice “size is irrelevant” compared to the young reference group age 16–30 years (p = 0.043). Amongst the respondents from the outpatient clinic, having high diabetes distress increased the likelihood to select the option “size is irrelevant” over “FreeStyle Libre 2 sensor” compared to low diabetes distress (p = 0.003). Of the 602 respondents who left a comment at this question, 36.7% indicated that their choice for maximal size was motivated primarily by comfort: the device should not be visible nor hinder daily activities.

As it is likely that several implants would need to be implanted for maximal efficacy, we asked how many devices a respondent would simultaneously accept to be cured of type 1 diabetes given that an incision of 5 cm would be needed per implant. Respondents could choose between 0 and 10 devices. Respondents indicated a median of 4 (IQR 3–6.75) implants to be acceptable (Figure 1). The option for 10 implants was selected by 186 (21.7%) people, of whom 110 (59.1%) commented that the number of devices is not relevant if it ensures a cure. Of 479 respondents that left a comment, 10.9% indicated scar formation, 11.5% recovery after surgery and 22.3% a balance between cure and daily discomfort to be considerations in selecting a maximal number of devices.

It is conceivable that the first generation of IDDs is functional for only a limited time. Therefore, respondents were informed that the cells in the implant would probably not be functional indefinitely, and that a replacement would be necessary under local anesthesia. We queried respondents what the minimal functional duration of an IDD should be before replacement (Table 3). A minimal functional duration of 3 months is the least desired option (13.2%). Replacement of an IDD of at most twice a year (minimal functional duration 6 months) was acceptable for 28.6%. A third (33.4%) of respondents would like the device to function for at least a year and 24.8% for at least 2 years. After correcting for method of recruitment, HbA1c and sex, respondents age 16–30 years were more likely to accept a minimal functional duration of 3–12 months when compared to those age 31–70 years (p < 0.001) and more likely to accept 6–12 months when compared to all other age categories (p-values 0.002–0.03).

Amongst respondents from the diabetes outpatient clinic, women were more likely than men to select a minimal functional duration of 24 months over 12 months (p = 0.01). Additionally, respondents age 31–50, and 51–70 years were more likely than those age 16–30 years to accept a minimal functional duration of 12 months compared to 6 months (p = 0.021 and p = 0.015, respectively). Of the 436 respondents who left a remark, 29.1% indicated that their choice revolved around minimizing emotional impact and impact on daily life due to hospital visits. Time to recovery and potential complications were important for 20%.

To gain more insights into which device characteristic was considered most important, the respondents distributed 10 points between device characteristics size, quantity and functional duration. Respondents preferred functional duration over quantity and size (4.9 ± 1.8 vs. 2.7 ± 1.2 vs. 2.3 ± 1.3 points, respectively, p < 0.001, Figure 2).

To evaluate what implant sites were acceptable, we asked what body parts were most preferable. The three most acceptable sites were the abdomen (65.7%), upper leg (63.7%), and upper arm (54.8%), whereas the forearm (15.7%), chest (15.2%) and lower leg (14%) were the three least accepted implant sites (Table 4). The only difference in sex was that men were more positive about the chest as implant site than women (20.1% vs. 11.7%, p < 0.001).

Islet delivery devices can potentially improve glycemic control and ideally lead to insulin independence. Respondents indicated in 34.8% of cases that they would only accept IDDs if it would cure them from diabetes (Table 3). In all other cases, various forms of improvement would also be acceptable. No longer suffering from hyperglycemia and hypoglycemia was the most selected non-curative improvement (35.2%).

Multiple device application strategies regarding islet delivery devices are currently considered. We surveyed the preference for three hypothetical scenarios (Table 2). Most respondents (61.1%) preferred a scenario with well-functioning cells that requires two surgical procedures over excellent-functioning cells requiring one surgical procedure and 10 min of daily care to supply oxygen (20.6%). A minority (6.1%) opted for moderately functioning cells after 1 surgical procedure. No preference was indicated by 12.3%.