Non-autoimmune diabetes common in African youth with T1D diagnosis

Non-autoimmune diabetes common in African youth with T1D diagnosis | Image Credit: © Chinnapong - stock.adobe.com.

A new study published in The Lancet Diabetes & Endocrinology reveals that most children and young adults diagnosed with type 1 diabetes (T1D) in sub-Saharan Africa may actually have a form of diabetes that is not autoimmune in origin. These findings could influence diagnostic and treatment approaches in the region and have broader implications for diabetes care globally.^1,2

“This is the first study across several Sub-Saharan African countries to use the same lab tests and genetic tools to learn more about type 1 diabetes. We've done similar research in the United States. with different groups, but what's exciting here is being able to compare results between Africa and the United States,” said Dana Dabelea, MD, PhD, distinguished professor and associate dean of research at the Colorado School of Public Health on the University of Colorado Anschutz Medical Campus, and a co-author of the study.

The cross-sectional study enrolled 894 participants with youth-onset, insulin-treated diabetes from Cameroon, Uganda, and South Africa. All participants were of self-reported Black African ethnicity, diagnosed before the age of 30 years, and had a body mass index under 30 kg/m². Investigators assessed autoimmunity using islet autoantibody testing (GADA, IA-2A, and ZnT8A) and evaluated genetic predisposition through a type 1 diabetes genetic risk score (GRS).

Among the participants, only 312 (34.9%) tested positive for one or more islet autoantibodies. This group exhibited features typical of autoimmune T1D, including severe insulin deficiency—225 of 272 (82.7%) had C-peptide levels below 200 pmol/L—and a high GRS for T1D. The remaining 582 participants (65.1%) were autoantibody-negative and showed significantly lower T1D GRS compared with autoantibody-positive individuals (median 9.66 vs 11.76; P<.0001). Despite the lack of autoimmune markers, most of this group also had severe insulin deficiency, suggesting a distinct form of non-autoimmune diabetes.

“This suggests that many young people in this region have a different form of T1D altogether and is not autoimmune in origin,” said Dabelea.

To contextualize these findings, the researchers compared data from their African cohort with participants in the U.S.-based SEARCH for Diabetes in Youth study. In SEARCH, a similar non-autoimmune diabetes pattern—autoantibody negativity and low GRS—was found in 15.1% of Black participants with youth-onset diabetes. In contrast, White participants in SEARCH who were autoantibody-negative still demonstrated high genetic susceptibility to T1D, indicating that their disease remained autoimmune in nature.

“The identification of this T1D diabetes subtype in Sub-Saharan African populations and among individuals of African ancestry in the U.S. suggests a potential ancestral or genetic link,” Dabelea said. “These findings highlight the need to consider alternative etiologies in this group, and a deeper understanding of the underlying mechanisms may provide important insights for future prevention and treatment strategies.”

The authors noted that while these autoantibody-negative cases in Africa do not appear consistent with type 2 diabetes or malnutrition-associated diabetes, their pathogenesis remains unclear. These individuals were not obese, had early-onset disease, and lacked the genetic features of type 2 diabetes. The study ruled out malnutrition-associated diabetes based on similar rates of rural residence, sex, and height across groups.

“This novel, non-autoimmune diabetes subtype observed in participants from these sub-Saharan African countries was usually accompanied by severe insulin deficiency and was not associated with the clinical or genetic features of type 2 diabetes,” the authors wrote.

The findings suggest that traditional markers used to diagnose T1D in high-income countries may not be sufficient in African populations, and that clinicians should consider alternative causes of insulin-deficient diabetes when evaluating young patients.

The study was supported by the UK National Institute for Health and Care Research and used standardized laboratory methods and population-specific autoantibody thresholds to ensure data accuracy. The authors emphasized the importance of further research into environmental and genetic factors that may underlie this atypical diabetes subtype.

References:

1. University of Colorado Anschutz Medical Campus. A new diabetes subtype identified in Sub-Saharan Africa and Black Americans, study finds. EurekAlert. July 21, 2025. Accessed July 24, 2025. https://www.eurekalert.org/news-releases/1091946
2. Katte JC, Squires S, Dehayem MY, et al. Non-autoimmune, insulin-deficient diabetes in children and young adults in Africa: evidence from the Young-Onset Diabetes in sub-Saharan Africa (YODA) cross-sectional study. The Lancet Diabetes & Endocrinology. Published online July 21, 2025. doi:https://doi.org/10.1016/S2213-8587(25)00120-2