Vascular Complications in Children and Young People with Type 1 Diabetes: A Worldwide Assessment of Diabetologists’ Adherence to International Recommendations

Long-term complications of type 1 diabetes (T1D), encompassing microvascular (diabetic nephropathy, retinopathy, and neuropathy) and macrovascular diseases, often manifest in adulthood and are associated with significant morbidity and mortality [1, 2]. Yet, early structural and functional changes can occur shortly after T1D onset [3].

International guidelines, specifically the Clinical Practice Consensus Guidelines (CPCG) from the International Society for Pediatric and Adolescent Diabetes (ISPAD), provide recommendations for screening, prevention and treatment of these complications in youth [1, 4]. These guidelines, adopted globally, consider different resource settings and undergo periodic updates based on emerging evidence [4, 5].

Previous studies revealed significant gaps between CPCG recommendations and their implementation in clinical practice, especially for retinopathy and risk factors (RFs) for macrovascular disease [6, 7]. This global survey evaluated the practices of physicians involved in pediatric diabetes care regarding screening, prevention and treatment of T1D vascular complications. It also explored potential barriers to implementing ISPAD CPCG in clinical practice.

Between March and October 2022, an anonymous, web-based survey was distributed to the ISPAD and JENIOUS – ISPAD’s early career researchers’ community. It was disseminated in English only, using the society’s social media channels and bulk e-mails.

The survey started with an electronic informed consent followed by 86 questions (online suppl. material, document 1; for all online suppl. material, see https://doi.org/10.1159/000539258) covering information about respondents’ background (section 1, including the country and continent of each clinical center according to the United Nations geoscheme), practices related to screening (age at initiation, frequency, method, health coverage and/or need of further individual’s financial contribution for screening), prevention and treatment of diabetic nephropathy, retinopathy, neuropathy and macrovascular diseases RFs (section 2) according to the ISPAD CPCG 2018 (Table 1). The third section included a self-assessment of physicians’ knowledge of the ISPAD CPCG [4]. For the multiple-choice questions in sections 2 and 3, one of the options always corresponded to the ISPAD CPCG recommendations. SPSS version 28.0.1.1 (IBM Corp, 2021) was used for data analysis. We include descriptive analyses and χ² tests to assess variations in practices and guideline adherence based on respondents’ countries’ income levels: high, upper-middle, lower-middle, and low income according to the World Bank country classification [8].

We received 175 responses from 62 countries (n = 105 [60.0%] female, median age 42.3 years, IQR 35.5–51.8; n = 125 [72.0%] from ISPAD members). Figure 1 displays the respondents’ distribution by continent and country income.

Approximately two-thirds of respondents initiated nephropathy and retinopathy screening according to the CPCG recommendations. Only half of them adhered to recommendations for neuropathy and macrovascular disease RFs. Lack of access to screening methods for neuropathy and macrovascular diseases RF was reported by 22.2% (n = 39) and 12% (n = 21) of respondents, respectively. Table 2 shows CPCG adherence data for T1D complications screening. The main reported barriers limiting access to screening methods were financial issues, the lack of laboratory and/or other equipment, and the need to refer the person with diabetes to another hospital and/or specialist.

While over 85% of respondents used the recommended screening method for nephropathy, retinopathy, and macrovascular disease RFs, the percentage was lower for neuropathy (58.8%, 103 respondents). Adherence to recommended screening frequency varied: 92% (161 respondents) for nephropathy, around two-thirds for neuropathy and macrovascular disease RFs, and only 17.7% (31 respondents) for retinopathy. Respondents from high- and low-income countries reported significantly lower adherence to neuropathy screening guidelines than those from middle-income countries (p = 0.002). Adherence to nephropathy recommendations was lower in respondents from low-middle and low-income compared to those from high-income countries (p = 0.007). Retinopathy screening frequency was less likely followed by respondents from middle-income countries than those from high- and low-income countries (p = 0.008) (online suppl. Fig. 1). No significant differences in adherence to CPCG were found between ISPAD and non-ISPAD members (data not shown).

Approximately 30% of respondents reported that individuals with T1D had to financially contribute to complications screening (33.5% [n = 58] for nephropathy, 30.5% [n = 53] for retinopathy, 30.1% [n = 54] for neuropathy, and 30.1% [n = 52] for macrovascular diseases RFs). Significant differences in health coverage and financial contribution for screening were found based on countries’ income. Continents with a higher proportion of respondents from low- and low-middle-income countries reported this barrier (online suppl. Table 1, all p < 0.001).

Most participants’ practices for treating T1D complications aligned with CPCG recommendations (Table 3), except for nephropathy. Only 33.1% (n = 58) of respondents followed CPCG for the treatment of elevated albuminuria and proteinuria, while 17.7% and 44% reported initiating angiotensin-converting enzyme inhibitors or angiotensin receptor blocking agents alone or in combination with CGCG suggested interventions. Knowledge of specific aspects of each complication is reported in Table 4, with around 44.5% (n = 78) of respondents being familiar with ISPAD CPCG content and 54% (n = 94) recognizing the importance of diabetes complication training.

Our study uncovered significant global variation in physicians’ adherence to the ISPAD CPCG 2018 on screening, prevention and treatment of pediatric T1D vascular complications. Starting screening at the age of 11 years with 2–5 years of diabetes duration allows the detection of early signs of vascular complications [3]. Yet adherence to this recommendation is suboptimal, particularly for neuropathy and RF for macrovascular disease. This finding aligns with previous studies reporting physicians’ limited awareness of vascular complications [9] and variable approaches to hypertension and dyslipidemia management [6, 10]. In addition, our results suggest reduced access to screening methods in resource-limited settings with a preference to follow local recommendations due to resource constraints. The survey underscored insufficient adherence to the recommended neuropathy screening methods based on history, physical examination, and clinical tests, underlining challenges in diagnosing this complication in youth with T1D, as outlined in a recent systematic review [11].

Significant heterogeneity for screening frequency emerged, whereby screening was performed more often for retinopathy (annually vs. every 2 years) but less frequently than recommended for neuropathy and macrovascular disease (every 2 years or every 3–5 years vs. annually). These findings may be explained by physicians following previous 2014 ISPAD CPCG or national guidelines that differ from the 2018 ISPAD CPCG [12, 13]. Raising awareness among physicians about optimal screening frequencies could ensure more efficient resource use. Notably, the 2022 ISPAD CPCG, published after this survey was closed, updated screening frequency for retinopathy based on the individual’s risk profile [1].

We also found financial and health system coverage disparities in complications screening based on country income, which likely impact the care and the health outcomes for youth with T1D [14]. Regarding the treatment of T1D vascular complications, respondents did not unanimously adhere to recommendations, especially for nephropathy. They often recommended earlier initiation of angiotensin-converting enzyme inhibitors or angiotensin receptor blocking agents therapy, alone or combined with the recommended interventions of reducing RFs exposure and, in case of elevated blood pressure, starting lifestyle interventions possibly due to awareness of their benefits in preventing diabetic nephropathy and macrovascular disease progression [15].

Only around 44% of respondents were very familiar with ISPAD CPCG content, and significant knowledge gaps emerged for biomarkers of diabetes complications and treatment of retinopathy and neuropathy. This underscores the critical need for educational initiatives to bridge these gaps and align clinical practice with CPCG recommendations.

This study has the typical survey-based limitations. The low representation of non-ISPAD members in Oceania and Africa and, in general, in low-income countries limits the generalizability of our results. The major strength is the comprehensive analysis of barriers to guideline implementation, enhancing understanding of T1D management complexities in resource-limited settings.

Our study highlighted global variation in CPCG adherence regarding T1D vascular complications, influenced by country income and healthcare disparities. It revealed knowledge gaps and urged efforts to enhance clinical care by improving guidelines adherence, reducing health disparities, and potentially improving the affordability and sustainability of practices for the management of T1D complications from childhood through to adulthood.

The authors would like to thank all survey respondents who shared their expertise, experience, and opinions by participating in the survey and making this study possible. We also thank the ISPAD organizing secretariat K.IT. Group GmbH, Berlin, for sending e-mails and reminders.

As an anonymous survey that did not collect any personal information or views of the survey participants, the study is exempt from ethical approval. Written informed consent to participate was not directly obtained but inferred by completion of the questionnaire/participation in the interview.

The authors have no conflicts of interest to declare.

No funding to declare.

Claudia Piona, Agata Chobot, Tiago Jeronimo Dos Santos, Elisa Giani, Loredana Marcovecchio, Claudio Maffeis, and Carine de Beaufort drafted, revised, and approved the survey. Claudia Piona analyzed data. Claudia Piona and Agata Chobot drafted the manuscript. All authors edited and discussed the manuscript. All authors approved the final version of the manuscript.

All data generated or analyzed during this study are included in this article and its supplementary material files. Further inquiries can be directed to the corresponding author.