Factors Associated with Insulin Resistance among Children and Adolescents Perinatally Infected with HIV-1 in the Pediatric HIV/AIDS Cohort Study

Abstract

Background/Aims: Because of prior inconsistent findings, we studied a large cohort of HIV-infected children to determine: (1) prevalence of insulin resistance (IR); (2) anthropometric and clinical correlates of IR, and (3) concomitant abnormalities of glucose tolerance. Methods: The study population consisted of 451 children from the Pediatric HIV/AIDS Cohort Study. The outcome of interest was HOMA-IR. Covariates included demographic, metabolic, growth, body composition, HIV laboratory tests, and treatment characteristics. Children meeting triggers for IR underwent oral glucose tolerance tests and hemoglobin A1c (HbA1c) measurements. Results: Among 402 children with glucose and insulin measurements, 15.2% had IR of whom 79% were pubertal. IR was associated with higher alanine aminotransferase, body mass index, and nadir CD4%, Tanner stage 5, and ever having received amprenavir. Of those with IR, three had impaired fasting glucose (IFG), three impaired glucose tolerance (IGT), one IFG and IGT, none diabetic glucose tolerance, and three HbA1c between 6.1 and 6.5%. Conclusion: In our cohort of HIV-infected adolescents, we observed a 15.2% prevalence of IR more closely linked to obesity than any other variable. This finding mirrors the high prevalence of obesity-mediated IR in American youth. However, associations with CD4 count and use of protease inhibitors may indicate some effect of HIV and/or its treatment.

Insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration

“…Mitochondrial markers were measured in those enrolled in the mitochondrial substudy. IR was defined as a homeostasis model assessment IR (HOMA-IR) score at least 4.0 (IR+ cases) in our pubertal or postpubertal sample [2]. …”

“…Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) are common among adults infected with HIV [1]. IR, a recognized precondition to T2DM, is also a concern in youth who are perinatally infected with HIV (pHIV), in which the prevalence is estimated to be between 15 and 52% [2,3]. …”

Perinatally infected adolescents living with human immunodeficiency virus (perinatally human immunodeficiency virus)

“…This fact suggests that the height loss accumulated Cruz MLS et al . HIV-infected adolescents higher body mass index values [31,32] . HIV-associated lipodystrophy is a particular cause of concern in adolescence, as the disordered distribution of the body fat -loss of fat in the face and lower limbs and enlarged dorsocervical fat pad and chest fat -might have significant repercussions in this stage of life, when the individual develops the adult body that serves to present oneself to the world.…”

Short Communication: The Relationship Between Mitochondrial Dysfunction and Insulin Resistance in HIV-Infected Children Receiving Antiretroviral Therapy

“…Approximately 15% of children in the Pediatric HIV/AIDS Cohort Study (PHACS) have insulin resistance, as determined by abnormal homeostatic model assessment of insulin resistance (HOMA-IR) scores. 17 In this population, insulin resistance has been associated with obesity, higher nadir CD4 + T cell counts, and amprenavir use, suggesting that HIV treatment may have some effect on the development of insulin resistance in HIV-infected children. 17 The primary objective of our study was to evaluate differences in mtDNA copy number and mitochondrial OXPHOS NADH dehydrogenase [Complex 1 (C1)] and cytochrome c oxidase [Complex 4 (C4)] enzyme activities among HIV-infected children with and without insulin resistance.…”

“…17 In this population, insulin resistance has been associated with obesity, higher nadir CD4 + T cell counts, and amprenavir use, suggesting that HIV treatment may have some effect on the development of insulin resistance in HIV-infected children. 17 The primary objective of our study was to evaluate differences in mtDNA copy number and mitochondrial OXPHOS NADH dehydrogenase [Complex 1 (C1)] and cytochrome c oxidase [Complex 4 (C4)] enzyme activities among HIV-infected children with and without insulin resistance. We chose to measure OXPHOS C1 and C4 activity since they are encoded for in mtDNA and are representative of both the beginning and end of the electron transport chain.…”