114-OR: T1DM in the Chronically Undernourished: Rural Ethiopia

T1DM results from the interaction of genetic and environmental factors; the classical phenotype has been based largely on people of European background. However, Africa is a continent of enormous genetic diversity and extreme environmental conditions; do these differences have an impact on the T1DM phenotype? A consecutive series of recently diagnosed insulin-dependent diabetic subjects (n=236, ≤35 years) and controls (n=200), were recruited from the ethnic Amhara of rural NW Ethiopia. We assessed their demographic and socio-economic characteristics, measured non-fasting C-peptide, diabetes-associated autoantibodies, and HLA-DRB1 alleles. With genome-wide genotyping we performed principal component analysis (PCA) and a genome-wide association study (GWAS), and calculated a T1DM genetic risk scores (GRS) to compare their genetic background with known European T1DM determinants. Patients presented with low BMI, stunted growth, and were insulin sensitive; only 15.3% had diabetes onset ≤15 years. C-peptide levels were low but not absent (P=0.03). 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 GADA as a single antibody; the prevalence of IA-2A and ZnT8A was low in all age groups. PCA showed that the Amhara genomes falls between those of ancestral European and ancestral African genomes. HLA-DRB1*03:01 and HLA-DRB1*04 were positively associated with diabetes while HLA-DRB1*15 was protective (P