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.

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.

• Authors: Jing Sun, Todd T Brown, Weiqun Tong, David Samuels, Phyllis Tien, Brahim Aissani, Bradley Aouizerat, Maria Villacres, Mark H Kuniholm, Deborah Gustafson, Katherine Michel, Mardge Cohen, Michael Schneider, Adaora A Adimora, Mohammed K Ali, Hector Bolivar, Todd Hulgan
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 71 Issue 8 Pg. e218-e225 (11 05 2020) ISSN: 1537-6591 [Electronic] United States
• PMID: 31927570 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 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].

Chemical References

• Blood Glucose
• DNA, Mitochondrial

Topics

• Black or African American
• Blood Glucose
• DNA, Mitochondrial (genetics)
• Diabetes Mellitus
• Diabetes Mellitus, Type 2 (complications, epidemiology, genetics)
• Female
• HIV
• HIV Infections (complications)
• Humans
• Incidence
• Insulin Resistance (genetics)