An international study co-authored by Professor Paul Rheeder of the University of Pretoria (UP) has revealed a previously unrecognised form of diabetes among young people in sub-Saharan Africa, challenging decades of clinical understanding and opening the door to improved diagnosis and treatment across the continent.

The research, published in The Lancet Diabetes & Endocrinology, investigated nearly 900 young Africans living with insulin-dependent diabetes and found that more than two-thirds did not display the autoimmune markers typically seen in classic type 1 diabetes. Instead, these individuals appear to have a distinct, non-autoimmune form of the disease, one that leaves them insulin-deficient but without the genetic or immune patterns found in either type 1 or type 2 diabetes.

The study forms part of the Young-Onset Diabetes in sub-Saharan Africa (YODA) project, a multi-country collaboration examining how diabetes manifests in African contexts. Researchers analysed blood samples from participants under 30 years old across Cameroon, Uganda, and South Africa, measuring immune and genetic markers associated with different forms of the disease.

Their analysis revealed that roughly 35 per cent of participants had autoimmune diabetes consistent with type 1, while 65 per cent had no detectable autoantibodies—signalling a non-autoimmune, insulin-deficient condition. These patients still required insulin to survive but represented an entirely different biological mechanism.

According to Professor Rheeder, this finding has implications for both clinical practice and public health. “Differentiating between Type 1 and Type 2 diabetes at presentation has always been a challenge in clinical practice. We have known that weight (BMI) and age were unreliable predictors but had relied heavily on the presence of antibodies to classify someone as having Type 1 diabetes. This has critical implications for the treatment options to lower the glucose. Type 1 diabetes always requires insulin whereas Type 2 diabetes is usually managed with tablets or only initially with insulin if they present with a hyperglycaemic emergency. This research now shows that people could still be Type 1 without antibodies.”

While the newly identified condition mirrors type 1 diabetes in its dependence on insulin, it differs in critical ways. The affected individuals tend to be slightly older at diagnosis, often in their late teens or early twenties. They also show lower rates of diabetic ketoacidosis at presentation and lack the autoimmune antibodies that destroy insulin-producing cells in type 1 patients.

The research team used advanced laboratory testing to examine four common islet autoantibodies (GAD65, IA-2, ZnT8, and insulin antibodies) and genetic risk scores derived from genome-wide association data. These analyses confirmed the absence of autoimmune activity in most cases, ruling out type 1 diabetes and distinguishing the condition from obesity-related type 2 diabetes.

“The challenge in Africa is that many patients are diagnosed in facilities with limited resources,” says Professor Rheeder. “Clinicians must often rely on the patient demographics, symptoms and glucose levels rather than sophisticated lab tests. By highlighting biological differences, this study helps clinicians recognise that not all insulin-dependent diabetes in young Africans is the same but classification in practice remains a challenge.”

Within the broader YODA consortium, the South African component, a joint effort between the Universities of Pretoria, Witwatersrand and Kwa Zulu Natal contributed an important component of the patient data.”

“We have long focused on understanding diseases as they truly present in our communities,” says Professor Rheeder. “Being part of this research allowed us to contribute African data to a global conversation, ensuring that discoveries are informed by our own populations rather than imported assumptions.”

He notes that the collaboration also provides opportunities for postgraduate training and capacity building in molecular diagnostics and endocrinology. “We are strengthening the pipeline of clinician-scientists who can carry this work forward,” he adds.

The findings challenge the assumption, common in textbooks and treatment protocols, that insulin-dependent diabetes in young people worldwide is largely autoimmune. By documenting a major non-autoimmune form in Africa, the study broadens the scientific understanding of how diabetes develops across different populations. The etiology of this type of diabetes observed in our study needs further investigation.

“This work demonstrates that diabetes is not a single uniform disease,” says Professor Rheeder. “It`s causes and characteristics vary depending on genetics, early nutrition, infections, and other environmental influences. For Africa, recognising this diversity is essential if we want effective prevention and care.”

For the University of Pretoria, the publication illustrates UP’s commitment to generating knowledge that addresses pressing public-health challenges.

“As researchers, our goal is not only to publish in high-impact journals like The Lancet but to ensure that the science we produce leads to tangible improvements in health,” Professor Rheeder says. “This study shows what is possible when African universities collaborate in world-class investigations into diseases that affect our own communities.”

He adds that the collaboration has strengthened ties between African and international partners, paving the way for future multicentre research on diabetes and metabolic diseases. The South African partners were privileged to contribute to this initiative of the University of Exeter (UK) and to partner with colleagues from Cameroon and Uganda. “Partnerships built on equality and shared expertise are essential for advancing science that truly benefits people,” he says.