Markers of Iron Status as Predictors, Effect Modifiers and Outcomes in an RCT of Growth Hormone and Rosiglitazone for Obesity and Insulin Resistance in Adults Living with HIV (P18-072-19)

Abstract

ObjectivesThis secondary analysis was conducted to examine the association of iron status with changes in insulin sensitivity (SI, μU*10–4*min1*ml−1) and visceral adipose tissue (VAT, L) as part of a randomized, double blind, placebo-controlled trial. This analysis was conducted to examine if serum ferritin (μg/L) and hemoglobin (Hb, g/dL)·independently predict changes in SI or VAT·are affected by treatment with rosiglitazone or recombinant human growth hormone (rhGH)·modify the effect of changes in SI or VAT in response to treatment among adults living with HIV with abdominal obesity and insulin-resistance participating in a randomized trial. MethodsIn a 2 × 2 double-blinded factorial design, participants were provided 4 mg rosiglitazone twice daily, 3 mg rhGH daily, a combination of rhGH + rosiglitazone, or double-placebo (control) for 12 weeks. Serum ferritin was adjusted for inflammation (C-reactive protein, mg/L; α-1-acid glycoprotein, g/L) using the Thurnham method. Generalized linear models were used to assess the association of baseline Hb and ferritin with changes in SI and VAT. Models were adjusted for the a priori determined covariates, age, treatment group, CD4 T-cell count and HIV-1 RNA viral load. Effect modification was assessed by including an interaction term between biomarker and intervention group. Generalized estimating equations were used to assess the effects of treatment on Hb and serum ferritin concentrations. ResultsAt baseline, there was no difference in serum ferritin (n = 47) or Hb (n = 45) across treatments; overall median (Q1, Q3) ferritin 95.60 (48.13, 151.00) μg/L, P = 0.13, Hb 14.40 (13.10,15.10) g/dL, P = 0.48. Neither marker of iron status was an independent predictor of changes in SI or in VAT. Compared to placebo at 12 weeks, Hb was significantly reduced by rosiglitazone (ß = −1.46, SE = 0.35, P < 0.0001), and by rhGH/rosiglitazone (ß = −0.93, SE = 0.30, P = 0.002) but not by rhGH alone. There was no significant effect of treatment on serum ferritin concentrations. Neither ferritin nor Hb modified the effect of intervention on changes in SI or VAT. ConclusionsIn this study among PLHIV, iron status was not an independent predictor or effect modifier of changes in SI or VAT. Treatments with rosiglitazone significantly reduced Hb concentration, which is consistent with adverse effects reported in previous clinical trials. Funding SourcesDivision of Nutritional Sciences, Cornell University.Weill Cornell Medicine, Cornell University