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Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults

BACKGROUND: The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to month...

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Autores principales: Mulindwa, Frank, Castelnuovo, Barbara, Brusselaers, Nele, Nabwana, Martin, Bollinger, Robert, Laker, Eva, Kiguba, Ronald, Schwarz, Jean-Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371155/
https://www.ncbi.nlm.nih.gov/pubmed/37502917
http://dx.doi.org/10.21203/rs.3.rs-3175598/v1
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author Mulindwa, Frank
Castelnuovo, Barbara
Brusselaers, Nele
Nabwana, Martin
Bollinger, Robert
Laker, Eva
Kiguba, Ronald
Schwarz, Jean-Marc
author_facet Mulindwa, Frank
Castelnuovo, Barbara
Brusselaers, Nele
Nabwana, Martin
Bollinger, Robert
Laker, Eva
Kiguba, Ronald
Schwarz, Jean-Marc
author_sort Mulindwa, Frank
collection PubMed
description BACKGROUND: The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance. METHODS: In this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%β respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance. RESULTS: Of the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28–37). Despite a trend towards an initial increase in both HOMA IR and HOMA%β at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%β at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: −0.46, 0.733, p = 0.648) and (difference in mean HOMA %β from baseline: 6.7, 95%CI: −13.4, 26.8, p = 0.506) respectively.
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spelling pubmed-103711552023-07-27 Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults Mulindwa, Frank Castelnuovo, Barbara Brusselaers, Nele Nabwana, Martin Bollinger, Robert Laker, Eva Kiguba, Ronald Schwarz, Jean-Marc Res Sq Article BACKGROUND: The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance. METHODS: In this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%β respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance. RESULTS: Of the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28–37). Despite a trend towards an initial increase in both HOMA IR and HOMA%β at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%β at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: −0.46, 0.733, p = 0.648) and (difference in mean HOMA %β from baseline: 6.7, 95%CI: −13.4, 26.8, p = 0.506) respectively. American Journal Experts 2023-07-20 /pmc/articles/PMC10371155/ /pubmed/37502917 http://dx.doi.org/10.21203/rs.3.rs-3175598/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Mulindwa, Frank
Castelnuovo, Barbara
Brusselaers, Nele
Nabwana, Martin
Bollinger, Robert
Laker, Eva
Kiguba, Ronald
Schwarz, Jean-Marc
Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults
title Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults
title_full Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults
title_fullStr Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults
title_full_unstemmed Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults
title_short Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults
title_sort dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of hiv-infected ugandan adults
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371155/
https://www.ncbi.nlm.nih.gov/pubmed/37502917
http://dx.doi.org/10.21203/rs.3.rs-3175598/v1
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