TY - JOUR
T1 - African Mitochondrial DNA Haplogroup L2 Is Associated with Slower Decline of β-cell Function and Lower Incidence of Diabetes Mellitus in Non-Hispanic, Black Women Living with Human Immunodeficiency Virus
AU - Sun, Jing
AU - Brown, Todd T.
AU - Tong, Weiqun
AU - Samuels, David
AU - Tien, Phyllis
AU - Aissani, Brahim
AU - Aouizerat, Bradley
AU - Villacres, Maria
AU - Kuniholm, Mark H.
AU - Gustafson, Deborah
AU - Michel, Katherine
AU - Cohen, Mardge
AU - Schneider, Michael
AU - Adimora, Adaora A.
AU - Ali, Mohammed K.
AU - Bolivar, Hector
AU - Hulgan, Todd
N1 - Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/5
Y1 - 2020/11/5
N2 - 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.
AB - 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.
KW - aging
KW - diabetes mellitus
KW - HIV
KW - mitochondrial genetics
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U2 - 10.1093/cid/ciaa026
DO - 10.1093/cid/ciaa026
M3 - Article
C2 - 31927570
AN - SCOPUS:85095861262
SN - 1058-4838
VL - 71
SP - E218-E225
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 8
ER -
