African Mitochondrial Dna Haplogroup L2 Is Associated With Slower Decline Of Beta-Cell Function And Lower Incidence Of Diabetes Mellitus In Non-Hispanic, Black Women Living With Human Immunodeficiency Virus

Background. Susceptibility to metabolic diseases may be influenced by mitochondria' genetic variability among people living with human immunodeficiency virus (HIV; PLWH), but remains unexplored in populations with African ancestry. We investigated the association between mitochondrial DNA (mtDNA) haplogroups and the homeostatic model assessments of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR), as well as incident diabetes mellitus (DM), among Black women living with or at risk for HIV.Methods. Women without DM who had fasting glucose (FG) and insulin (FI) data for >= 2 visits were included. Haplogroups were inferred from genotyping data using HaploGrep. HOMA-B and HOMA-IR were calculated using FG and FI data. Incident DM was defined by a combination of FG >= 126 mg/dL, the use of DM medication, a DM diagnosis, or hemoglobin A1c >= 6.5%. We compared IIOMA-B, HOMA-IR, and incident DM by haplogroups and assessed the associations between HOMA-B and HOMA-IR and DM by haplogroup.Results. Of 1288 women (933 living with HIV and 355 living without HIV), PLWH had higher initial HOMA-B and HOMA-IR than people living without HIV. PLWH with haplogroup L2 had a slower decline in HOMA-B per year (P-interaction = .02) and a lower risk of incident DM (hazard ratio [HR], 0.51; 95% confidence interval [CI], .32-.82) than PLWI I with other haplogroups after adjustments for age, body mass index, combination antiretroviral therapy use, CD4 cell counts, and HIV RNA. The impact of HOMA-IR on incident DM was less significant in those with haplogroup L2, compared to non-L2 (HR, 1.28 [95% CI, .70-2.38] vs 4.13 [95% CI, 3.28-5.22], respectively; P-interaction < .01), among PLWH.Conclusions. Mitochondrial genetic variation is associated with beta-cell functions and incident DM in non-IIispanic, Black women with HIV and alters the relationship between insulin resistance and DM.