BACKGROUND: Black and African patients with type 2 diabetes have a greater frequency and more severe vascular complications of the disease, even after correction for socioeconomic factors. Asymptomatic sickle cell trait (SCT; hemoglobin AS) is also common among black Africans and may independently cause endothelial damage, manifested as isolated target organ complication or infarction. We examined the possibility that patients with concurrent type 2 diabetes and SCT may be predisposed to more frequent or severe diabetic macro- or microvascular complications than those without SCT. METHODS: Fifty-two type 2 diabetic patients were divided into four groups, according to gender and hemoglobin genotype (normal: AA or SCT: AS). The groups were well matched for age and for clinical and demographic parameters. Diabetic complications were assessed in each patient and scored. Hemoglobin genotype was determined by hemoglobin-gel electrophoresis. Statistical comparisons were made between the groups. RESULTS: The composite complication score for vascular disease differed significantly according to gender and genotype (p<0.027 ANOVA). Male diabetics with SCT had a higher risk ratio (RR 1.6, p<0.02) for complications than those with normal hemoglobin; however, this was not the case with female diabetics. Among the male diabetics with SCT, there was a significantly greater proportion with proteinuria (p<0.02) or retinopathy (p<0.05) than among those with a normal hemoglobin genotype. Multiple regression analysis showed that gender and SCT were independent predictors of the vascular complication severity score and that exclusion of hemoglobin genotype weakened the predictability of the regression. A significantly higher proportion of male than female diabetics had at least one detectable complication. Systolic or diastolic blood pressure had no significant impact on the regressions. CONCLUSION: Male gender and SCT may adversely affect the expression of microvascular diabetic complications in Africans. Diabetic patients from populations predisposed to the sickle gene should be screened for the trait as part of their initial risk assessment. Large-scale studies on the impact of hemoglobin genotype on diabetic complications are clearly indicated.