Type 2 diabetes mellitus, or T2DM, is a metabolic disorder characterized by chronic hyperglycemia resulting from insulin resistance and progressive failure of insulin-secreting pancreatic beta cells. It accounts for the overwhelming majority of diabetes cases globally, and its prevalence has surged in recent decades, driven by aging populations, urbanization, obesity and sedentary lifestyles. Saudi Arabia sits near the epicenter of this crisis, with national surveys consistently reporting that a substantial fraction of adults live with the condition or its precursor states. Against this backdrop, researchers have increasingly looked beyond lifestyle factors to identify inherited traits that might modulate individual susceptibility.

The ABO blood group system, first described by Karl Landsteiner in 1901, classifies human blood into the A, B, AB and O phenotypes based on the presence or absence of specific carbohydrate antigens on the surface of red blood cells. These antigens are synthesized by glycosyltransferase enzymes encoded by the ABO gene on chromosome 9. The Rhesus system, the second most clinically important blood group classification, is defined largely by the presence or absence of the D antigen. While these systems are best known for their role in transfusion medicine and pregnancy compatibility, a growing body of research has implicated ABO type in a surprising range of conditions, including venous thromboembolism, cardiovascular disease, certain cancers and even susceptibility to some infections.

Previous studies exploring the link between blood groups and diabetes have produced contradictory results, with some reporting elevated risk for particular phenotypes and others finding no association at all. The authors of the new study attribute this inconsistency partly to genetic and geographic differences between the populations examined. Blood group distributions vary considerably across ethnic groups, and the genetic architecture of diabetes risk differs between populations. To address the gap, the research team set out to evaluate the association between ABO and Rh blood groups and the occurrence of T2DM in a Saudi Arabian cohort, a population that had been underrepresented in the existing literature.

The study was designed as a cross-sectional analysis conducted at King Abdulaziz Medical City, spanning January 2019 to December 2023. The investigators enrolled a total of 666 subjects: 350 patients diagnosed with type 2 diabetes and 316 healthy blood donors who served as controls. Because the analysis relied on de-identified retrospective data, the Institutional Review Board of the King Abdullah International Medical Research Centre approved the study and waived the requirement for informed consent. The team then compared the frequency of each ABO and Rh phenotype between the diabetic and control groups, using chi-square tests to detect differences in distribution and multivariable logistic regression to estimate the odds of T2DM associated with each blood type while accounting for potential confounding factors.

The results were striking. The overall distribution of ABO blood groups differed significantly between patients with T2DM and healthy controls, with the difference reaching a p-value of 0.0005. Blood groups A, B and AB were all more frequent among the diabetic patients than among the controls, whereas blood group O was markedly more prevalent in the control group, accounting for 56.2 percent of controls compared with only 43.8 percent of diabetics. When the researchers applied multivariable logistic regression to disentangle the independent contribution of each phenotype, only two associations survived statistical scrutiny. Phenotype B was significantly associated with increased odds of T2DM, with a p-value of 0.017, while blood type O was associated with lower odds of the disease, with a p-value below 0.001.

Notably, the Rhesus blood group showed no significant relationship with diabetes occurrence in this cohort. The researchers also stratified their analysis by sex and by glucose test categories, including fasting blood sugar and hemoglobin A1c, a long-term marker of glycemic control. Neither stratification revealed differences in the prevalence of ABO or Rh phenotypes between diabetics and controls, with all comparisons yielding p-values above 0.05. This suggests that the blood group effect, if real, operates on the overall occurrence of the disease rather than on its severity or glycemic presentation, and that it affects men and women similarly.

What biological mechanisms could underlie such an association? The authors point to several plausible pathways that have been proposed in the broader literature. ABO blood group status influences plasma levels of von Willebrand factor and factor VIII, proteins central to blood coagulation, and group O individuals characteristically have lower levels of both. Because type 2 diabetes is strongly linked to vascular complications and chronic low-grade inflammation, differences in endothelial function, coagulability and inflammatory signaling between blood types could plausibly modulate metabolic risk. ABO antigens are also expressed not only on red blood cells but on the surfaces of many epithelial and endothelial cells and are secreted into body fluids in secretor-positive individuals, raising the possibility of more direct effects on glucose metabolism, gut microbiome composition or insulin signaling pathways. The authors themselves, however, are careful to note that the mechanisms remain unexplored and that their study was not designed to test them.

The researchers conclude that individuals with blood group B appear to have higher odds of T2DM compared with other ABO phenotypes, while those with blood group O show a protective association. They emphasize that further research is needed to validate these findings and to explore the underlying mechanisms in larger, prospective studies. The caution is warranted. Cross-sectional designs capture a single moment in time and cannot establish whether blood type precedes disease onset, and the control group of healthy blood donors may not perfectly represent the general population. Residual confounding by age, body mass index, family history and lifestyle factors cannot be excluded, even with multivariable adjustment. The authors also acknowledge that earlier studies in other populations have yielded inconsistent results, so the pattern observed in this Saudi cohort may not generalize universally.

Nevertheless, the study offers a tantalizing glimpse of how an inherited, easily measurable trait might one day contribute to diabetes risk assessment. Blood group typing is inexpensive, rapid and already performed routinely in clinical settings, so if the association is confirmed and the effect size is meaningful, ABO phenotype could conceivably be incorporated into multifactorial risk models alongside age, weight, family history and metabolic markers. For now, the message for the public remains grounded in established prevention: maintaining a healthy weight, staying physically active and monitoring blood glucose are the proven defenses against type 2 diabetes, regardless of whether one’s red cells carry A, B, both or neither antigen. But as genetic epidemiology continues to probe the unexpected corners of human biology, the idea that a transfusion card could hint at metabolic destiny is no longer quite so far-fetched.

Subject of Research: The association between ABO and Rhesus blood groups and the occurrence of type 2 diabetes mellitus in a Saudi Arabian cohort

Article Title: The association of ABO and Rhesus blood groups with the occurrence of type 2 diabetes mellitus

Article References: The association of ABO and Rhesus blood groups with the occurrence of type 2 diabetes mellitus. (n.d.). https://doi.org/10.1186/s12902-026-02640-0

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02640-0

Keywords: ABO blood group, Rhesus factor, type 2 diabetes, diabetes risk, blood type O, blood group B, cross-sectional study, Saudi Arabia, logistic regression, endocrine disorders, genetic association, metabolic disease