Prospective Study of Non-Autoimmune Insulin-Deficient Diabetes Subtype in Young Individuals in sub-Saharan Africa (PANDA study): study protocol.

INTRODUCTION: Diabetes affects over 24 million people in Africa, with type 1 and type 2 diabetes being the most recognised forms. Recent studies in sub-Saharan Africa have identified a substantial proportion of children and young adults with clinically diagnosed type 1 diabetes (T1D) who lack evidence of islet autoimmunity despite severe insulin deficiency, suggesting a distinct non-autoimmune insulin-deficient diabetes subtype (NAID). This study aims to characterise the clinical phenotype, assess the underlying pathophysiology and longitudinal progression of this diabetes subtype. METHODS AND ANALYSIS: This is a prospective observational study comprising a cross-sectional comparative analysis and a 3-year longitudinal follow-up cohort. The study will recruit 355 children and young adults aged below 25 years with recently (diabetes duration ≤12 months) diagnosed T1D, with an anticipated estimate of 240 NAID and 115 autoimmune T1D cases. In addition, a minimum of 240 age-matched and sex-matched individuals without diabetes will be recruited as healthy controls. Participants will undergo detailed clinical phenotyping, laboratory assessment including islet autoantibody and C-peptide testing and biospecimen collection for biomarker analyses. A nested mechanistic substudy will include a mixed meal tolerance test and pancreatic MRI to assess pancreatic function and structure. Participants with diabetes will be followed for 3 years to assess longitudinal changes in endogenous insulin secretion, glycaemic response and acute metabolic complications. The study will provide the first prospective characterisation of NAID in sub-Saharan Africa and is expected to improve understanding of its clinical phenotype, natural history and underlying biology, thereby informing future diagnostic and therapeutic strategies. ETHICS AND DISSEMINATION: This study protocol was approved by the National Ethics Committee for Human Health Research (IRB No 2026/05/1930/CE/CNERSH/SP/SPA). All participants will provide written informed consent or assent with parental consent, where appropriate, before enrolment into the study. Research findings will be disseminated through peer-reviewed publications, policy briefs, stakeholder meetings and presentations at national and international scientific conferences. TRIAL REGISTRATION NUMBER: ISRCTN15312527.