Jing Sun1, Todd T Brown1,2, Weiqun Tong1, David Samuels3, Phyllis Tien4,5, Brahim Aissani6, Bradley Aouizerat7, Maria Villacres8, Mark H Kuniholm9, Deborah Gustafson10, Katherine Michel11, Mardge Cohen12, Michael Schneider1, Adaora A Adimora13, Mohammed K Ali14, Hector Bolivar15, Todd Hulgan16,17. 1. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA. 2. Department of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 3. Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 4. Department of Medicine, Division of Infectious Disease, University of California-San Francisco, San Francisco, CA, USA. 5. Department of Veterans Affairs Medical Center, San Francisco, San Francisco, CA, USA. 6. Department of Epidemiology, University of Alabama-Birmingham, Birmingham, Alabama, USA. 7. Rory Meyers College of Nursing, New York University, New York, New York, USA. 8. Department of Medicine, University of Southern California, Los Angeles, California, USA. 9. Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York, USA. 10. Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, New York, USA. 11. Department of Medicine, Georgetown University, Washington, DC, USA. 12. Hektoen Institute for Medical Research, Chicago, Illinois, USA. 13. School of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 14. Department of Epidemiology, Emory University, Atlanta, Georgia, USA. 15. Miller School of Medicine, Infectious Diseases Division, University of Miami, Miami, Florida, USA. 16. Tennessee Valley Healthcare System-Veterans Affairs Hospital, Nashville, Tennessee, USA. 17. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Abstract
BACKGROUND: Susceptibility to metabolic diseases may be influenced by mitochondrial 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 β-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 HOMA-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 (Pinteraction = .02) and a lower risk of incident DM (hazard ratio [HR], 0.51; 95% confidence interval [CI], .32-.82) than PLWH 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; Pinteraction < .01), among PLWH. CONCLUSIONS: Mitochondrial genetic variation is associated with β-cell functions and incident DM in non-Hispanic, Black women with HIV and alters the relationship between insulin resistance and DM.
BACKGROUND: Susceptibility to metabolic diseases may be influenced by mitochondrial 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 β-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 HOMA-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 (Pinteraction = .02) and a lower risk of incident DM (hazard ratio [HR], 0.51; 95% confidence interval [CI], .32-.82) than PLWH 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; Pinteraction < .01), among PLWH. CONCLUSIONS: Mitochondrial genetic variation is associated with β-cell functions and incident DM in non-Hispanic, Black women with HIV and alters the relationship between insulin resistance and DM.
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