Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia.

AIMS/HYPOTHESIS: We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations. METHODS: A study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes (n = 236, ≤35 years) and control participants (n = 200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and HLA-DRB1 alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants. RESULTS: Patients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ≤15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ≤15, 16-25 and 26-35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes. HLA-DRB1*03:01 (p = 0.0014) and HLA-DRB1*04 (p = 0.0001) were positively associated with this form of diabetes, while HLA-DRB1*15 was protective (p < 0.0001). The mean type 1 diabetes genetic risk score (derived from European data) was higher in patients than control participants (p = 1.60 × 10-7). Interestingly, despite the modest sample size, autoantibody-positive patients revealed evidence of association with SNPs in the well-characterised MHC region, already known to explain half of type 1 diabetes heritability in Europeans. CONCLUSIONS/INTERPRETATION: The majority of patients with insulin-dependent diabetes in rural North-West Ethiopia have the immunogenetic characteristics of autoimmune type 1 diabetes. Phenotypic differences between type 1 diabetes in rural North-West Ethiopia and the industrialised world remain unexplained.

Type 1 diabetes mellitus in the context of high levels of rural deprivation: differences in demographic and anthropometric characteristics between urban and rural cases in NW Ethiopia.

Background: While there is increasing evidence for an altered clinical phenotype of Type 1 diabetes in several low-and middle-income countries, little is known about urban-rural differences and how the greater poverty of rural environments may alter the pattern of disease. Objective: Investigation of urban-rural differences in demographic and anthropometric characteristics of type 1 diabetes in a resource-poor setting. Research design and methods: Analysis of a unique case register, comprising all patients (rural and urban) presenting with Type 1 diabetes over a 20 yr. period in a poor, geographically defined area in northwest Ethiopia. The records included age, sex, place of residence, together with height and weight at the clinical onset. Results: A total of 1682 new cases of Type 1 diabetes were registered with a mean age of onset of 31.2 (SD 13.4) yr. The patients were thin with 1/3 presenting with a body mass index (BMI) <17kg/m2. There was a striking male predominance of cases when clinical onset was between 20 and 35 yr., this was more marked in the very poor rural dwellers compared to the urban population. While most patients with Type 1 diabetes presented with low BMIs and reduced height, stunting preferentially affected rural men. Conclusions: These data have led to the hypothesis that complex interactions among poor socioeconomic conditions in early life affect both pancreatic function and the development of autoimmunity and provide a possible explanation of the unusual phenotype of Type 1 diabetes in this very poor community.