JDRF Request for Applications: Glycemic and Beta Cell Monitoring in Individuals at Risk of Type 1 Diabetes

Funding over a maximum of three years for projects that will aid the translation of risk assessment tools for type 1 diabetes into clinical use, focusing on identifying individuals progressing from the presymptomatic disease stage to clinical diagnosis and the improvement of current or new metabolic risk assessment tools and their integration into clinically and commercially utilised testing platforms.

JDRF, based in the United States, is an international organisation that funds innovative research to accelerate breakthroughs to advance the treatment, prevention and cure of type-1 diabetes (T1D).

This Request for Applications – ‘Glycemic and Beta Cell Monitoring in Individuals at Risk of Type 1 Diabetes’ – is seeking to solicit proposals for pioneering research aimed at advancing understanding of glycaemic changes during disease progression in presymptomatic (Stage 1 and 2) individuals at high risk of T1D, with the potential to improve progression biomarkers and monitoring their transition to clinical diagnosis (Stage 3).

The knowledge gained from research supported by this RFA may eventually be applicable to support regulatory decisions and be part of monitoring guidelines, enabling more effective early identification and timely intervention by healthcare professionals, including the use of innovative drug therapies, immunotherapies and other promising treatments current in clinical trials. As such, its implementation would mark a significant milestone in the pursuit of delaying or preventing T1D and its associated complications – one of the key objectives of JDRF, as described in its Research Strategy.

Accordingly, LOI’s are sought for projects that will aid the translation of risk assessment tools for T1D into clinical use, with a focus on the improvement of current or new metabolic risk assessment tools and their integration into clinically and commercially utilised testing platforms.

Proposals should aim to prioritise validating optimal measurements for glycaemic control, with a focus on monitoring alternatives such as blood glucose dysregulation (using fingersticks or CGMs) and beta cell function (C-peptide). The objective of this emphasis is to enable the timely detection of individuals as they transition to Stage 3 T1D.

Importantly, the correlation of data measurements from the classic measurements of HbA1c, oral glucose tolerance tests (OGTT) and mixed meal tolerance tests (MMTT) is essential to provide context on how they compare to alternative approaches. Of particular interest is the development of glycaemic approaches that are implementable in clinical or public health laboratories, as well as at home testing.

Grant support is available over a maximum of three years for projects that aim to identify and/or further validate biomarkers of progression to clinical T1D, including, but not limited to:

• HbA1c measurements that fall outside of the optimal range, but also ≥10% increases within optimal ranges.
• Fasting or pre/post-prandial home fingerstick blood glucose monitoring.
• Percentage of CGM time spent above 120-140 mg/dL, using time in range (TIR) and/or glucose management indicators (GMI).
• In-clinic vs at-home measures of beta cell function by OGTT, their timing and serial approaches.

Encouragement is given to research proposals that address one or more of the following areas:

• Longitudinal studies: Introducing an additional parameter to existing longitudinal studies, with the goal of incorporating glycaemic monitoring approaches such as CGMs or C-peptide. This expansion aims to enhance the follow-up of current individuals enrolled, providing a more comprehensive understanding of measurements and contributing valuable insights to refine diabetes management strategies.
• Retrospective studies: Conducting a retrospective analysis across longitudinal studies to deepen understanding of historical data related to different glycaemic monitoring approaches, including CGMs or C-peptide. This analysis aims to assess the effectiveness of these alternatives on identifying individuals at risk of disease progression and compare their reliability to traditional monitoring methods such as HbA1c and OGTT/MMT analysis.
• Comparative studies between children and adults with clinical onset of T1D: To explore and compare data from longitudinal and interventional studies to understand the unique aspects of disease progression in paediatric populations versus adults. Additionally, JDRF has particular interested in adult monitoring follow-up from research studies, aiming to comprehensively assess and analyse the long-term outcomes and inform tailored strategies for the effective management of and interventions in this population.
• Monitoring of immunotherapy treatments: Implementing follow-up glycaemic monitoring for individuals undergoing disease modifying therapies, whether in FDA-approved treatments (eg teplizumab) or enrolled in other ongoing clinical trials. Establishing a robust system for continuous monitoring, allowing for better follow-up of patients and aiming to improve their outcomes through optimised glycaemic management.
• Clinical trials and the impact of glycaemic monitoring approaches: Investigate the relationship between clinical outcomes and C-peptide data for use in clinical trial settings. This aspect aims to elucidate the potential value of C-peptide as a biomarker of disease progression in the context of clinical trials, contributing to the development of more effective and targeted monitoring approaches.
• Advanced monitoring technologies: Develop and evaluate innovative monitoring technologies that provide real-time data on beta cell function and glucose control in presymptomatic individuals before and after they progress to clinical disease. The integration of cutting-edge monitoring devices with C-peptide assessment is critical for a comprehensive understanding of the disease progression.
• Biomarker validation: Research projects focused on validating novel biomarkers of disease progression and beta cell loss (eg immune or beta cell biomarkers), while also evaluating their relationship with C-peptide levels and glycaemic control. These biomarkers will be proven as indicators of disease progression before clinical diagnosis.
• Ethnic and gender diversity and disparities: Investigate the impact of ethnicity on glucose management and C-peptide levels in T1D progression.

A key goal of this RFA is to profile the decline of C-peptide before clinical onset. The RFA will support the analysis of existing datasets from natural or clinical studies that include measurement of C-peptide used to monitor endogenous insulin production before and after diagnosis in individuals at risk.