Acute hyperinsulinemia effects on systemic markers of immune activation in HIV

O’Malley, Timothy K; Burdo, Tricia H.; Robinson, Jake A.; Fitch, Kathleen V.; Grinspoon, Steven; Srinivasa, Suman

doi:10.1097/qad.0000000000001545

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…Insulin resistance has been widely reported in adults with HIV [37] and inflammation and immune activation, which have been associated with non-AIDS complications in HIV. Specifically, higher insulin resistance, as measured by HOMA-IR or oral glucose tolerance test in HIV, has been associated with classical monocyte subsets and monocyte activation [12,38] and with bacterial translocation [39][40][41] but not gut barrier dysfunction [42]. We have previously published that this Ugandan cohort with PHIV has increased T cell activation and evidence of a leaky gut compared with children without HIV, which worsened over time [43,44]; however, in this analysis, none of the markers of systemic inflammation, immune activation, gut integrity, or translocation were associated with HOMA-IR in PHIV.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with insulin resistance in a longitudinal study of Ugandan youth with and without HIV

Dirajlal-Fargo,

Strah,

Ailstock

et al. 2023

Aids

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Prospective investigations from sub-Saharan Africa on metabolic complications in youth with perinatally acquired HIV (PHIV) are lacking. We investigated the changes in insulin resistance in Ugandan PHIV on ART and uninfected controls and their relationship with inflammation, HIV and cardiovascular disease (CVD) risk factors. Participants 10–18 years of age were included in a prospective study performed in Kampala, Uganda. We compared baseline and changes in insulin resistance (by HOMA-IR) and in markers of inflammation at baseline and 96 weeks. PHIVs were on ART with HIV-1 RNA level ≤400 c/mL. Generalized Estimating Equation models were used to assess associations between HOMA-IR, and demographic as well as inflammatory markers. Of the 197 participants recruited at baseline (101 PHIV, 96 HIV-), 168 (89 PHIV, 79 HIV-) had measurements at 96 weeks. At baseline, median (Q1, Q3) age was 13 years (11,15), 53.5% were females, median CD4+ cell counts were 988 cells/μL (631, 1310). At baseline, HOMA-IR was significantly higher in PHIV compared to controls (p = 0.03). HOMA-IR did not significantly change by week 96 in either group, and at 96 weeks, was similar between groups (p = 0.15). HOMA-IR was not associated with any inflammatory markers, or any specific ART. In longitudinal analysis, age and Tanner stage remained associated with higher HOMA-IR throughout the study period, after adjusting for HIV status. In this longitudinal cohort of virally suppressed PHIV in Uganda, PHIV have decreased insulin sensitivity compared to controls, however this difference does not persist through adolescence. ART and immune activation do not appear to affect glucose homeostasis in this population.

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Section: Discussionmentioning

confidence: 99%

Factors associated with insulin resistance in a longitudinal study of Ugandan youth with and without HIV

Dirajlal-Fargo,

Strah,

Ailstock

et al. 2023

Aids

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“…Mounting evidence over the last several years has highlighted the potential contribution of an impaired gut microbial barrier and translocated bacterial products to sequelae of chronic inflammation and immune activation in persons with HIV [71, 72]. Acute hyperinsulinemia during OGTT in persons with and without HIV was associated with increases in soluble CD14, a marker of monocyte activation related to lipopolysaccharide (LPS) [73]. Other recent studies have reported correlations between higher IR (by OGTT) and plasma LPS level in persons on ART [74], and between the presence of bacterial DNA products and elevations of hemoglobin A1c over time [75].…”

Section: Risk Factors For Insulin Resistance Potentially Unique To Ormentioning

confidence: 99%

Factors Associated With Insulin Resistance in Adults With HIV Receiving Contemporary Antiretroviral Therapy: a Brief Update

Hulgan

2018

Curr HIV/AIDS Rep

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IR remains common in persons with HIV, even those receiving contemporary ART. Generalized and abdominal obesity and ectopic fat are correlates of IR, and emerging data have identified associations with biomarkers of inflammation and immune activation. Small studies suggest associations between mitochondria and IR. In ART-naïve individuals, IR increased within 4 weeks of starting ART in persons receiving contemporary boosted protease inhibitors or an integrase inhibitor. The importance of IR in non-diabetic persons with HIV will continue to grow as the population ages and obesity increases. Non-invasive estimates of IR appear to perform well in persons with HIV, but clinically relevant cutoffs are uncertain. Unexpected metabolic effects of newer HIV integrase inhibitors have been reported; thus, careful observation for and studies of IR are still warranted.

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Randomized, Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Metabolic and Inflammatory Indices in HIV

Srinivasa

Fitch

Wong

et al. 2018

The Journal of Clinical Endocrinology &Amp; Metabolism

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Acute hyperinsulinemia effects on systemic markers of immune activation in HIV

Cited by 3 publications

References 13 publications

Factors associated with insulin resistance in a longitudinal study of Ugandan youth with and without HIV

Factors associated with insulin resistance in a longitudinal study of Ugandan youth with and without HIV

Factors Associated With Insulin Resistance in Adults With HIV Receiving Contemporary Antiretroviral Therapy: a Brief Update

Randomized, Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Metabolic and Inflammatory Indices in HIV

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