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Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir

BACKGROUND: Following reports of anti-retroviral therapy (ART) experienced Ugandan people living with HIV (PLHIV) presenting with diabetic ketoacidosis weeks to months following a switch to dolutegravir (DTG), the Uganda Ministry of Health recommended withholding DTG in both ART naïve and experience...

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Autores principales: Mulindwa, Frank, Castelnuovo, Barbara, Brusselaers, Nele, Bollinger, Robert, Rhein, Joshua, Edrisa, Mutebi, Buzibye, Allan, Amutuhaire, Willington, Yendewa, George, Nabaggala, Sarah, Odongpiny, Eva Laker Agnes, Kiguba, Ronald, Nakawooza, Aisha, Dujanga, Simon, Nabwana, Martin, Schwarz, Jean-Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009965/
https://www.ncbi.nlm.nih.gov/pubmed/36915103
http://dx.doi.org/10.1186/s12981-023-00510-6
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author Mulindwa, Frank
Castelnuovo, Barbara
Brusselaers, Nele
Bollinger, Robert
Rhein, Joshua
Edrisa, Mutebi
Buzibye, Allan
Amutuhaire, Willington
Yendewa, George
Nabaggala, Sarah
Odongpiny, Eva Laker Agnes
Kiguba, Ronald
Nakawooza, Aisha
Dujanga, Simon
Nabwana, Martin
Schwarz, Jean-Marc
author_facet Mulindwa, Frank
Castelnuovo, Barbara
Brusselaers, Nele
Bollinger, Robert
Rhein, Joshua
Edrisa, Mutebi
Buzibye, Allan
Amutuhaire, Willington
Yendewa, George
Nabaggala, Sarah
Odongpiny, Eva Laker Agnes
Kiguba, Ronald
Nakawooza, Aisha
Dujanga, Simon
Nabwana, Martin
Schwarz, Jean-Marc
author_sort Mulindwa, Frank
collection PubMed
description BACKGROUND: Following reports of anti-retroviral therapy (ART) experienced Ugandan people living with HIV (PLHIV) presenting with diabetic ketoacidosis weeks to months following a switch to dolutegravir (DTG), the Uganda Ministry of Health recommended withholding DTG in both ART naïve and experienced PLHIV with diabetes mellitus (T2DM), as well as 3-monthly blood glucose monitoring for patients with T2DM risk factors. We sought to determine if the risk of T2DM is indeed heightened in nondiabetic ART naïve Ugandan PLHIV over the first 48 weeks on DTG. METHODS: Between January and October 2021, 243 PLHIV without T2DM were initiated on DTG based ART for 48 weeks. Two-hour oral glucose tolerance tests (2-h OGTT) were performed at baseline, 12, and 36 weeks; fasting blood glucose (FBG) was measured at 24 and 48 weeks. The primary outcome was the incidence of T2DM. Secondary outcomes included: incidence of pre-Diabetes Mellitus (pre-DM), median change in FBG from baseline to week 48 and 2-h blood glucose (2hBG) from baseline to week 36. Linear regression models were used to determine adjusted differences in FBG and 2hBG from baseline to weeks 48 and 36 respectively. RESULTS: The incidence of T2DM was 4 cases per 1000 PY (1/243) and pre-DM, 240 cases per 1000 person years (PY) (54/243). There was a significant increase in FBG from baseline to week 48 [median change from baseline (FBG): 3.6 mg/dl, interquartile range (IQR): − 3.6, 7.2, p-value (p) = 0.005] and significant reduction in 2hBG (2hBG: − 7.26 mg/dl, IQR: − 21.6, 14.4, p = 0.024) at week 36. A high CD4 count and increased waist circumference were associated with 2hBG increase at week 36. CONCLUSION: We demonstrated a low incidence of T2DM in Ugandan ART-naïve patients receiving DTG. We also demonstrated that longitudinal changes in BG were independent of conventional risk factors of T2DM in the first 48 weeks of therapy. Restricting the use of dolutegravir in Ugandan ART naïve patients perceived to be high risk for diabetes mellitus may be unwarranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12981-023-00510-6.
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spelling pubmed-100099652023-03-14 Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir Mulindwa, Frank Castelnuovo, Barbara Brusselaers, Nele Bollinger, Robert Rhein, Joshua Edrisa, Mutebi Buzibye, Allan Amutuhaire, Willington Yendewa, George Nabaggala, Sarah Odongpiny, Eva Laker Agnes Kiguba, Ronald Nakawooza, Aisha Dujanga, Simon Nabwana, Martin Schwarz, Jean-Marc AIDS Res Ther Research BACKGROUND: Following reports of anti-retroviral therapy (ART) experienced Ugandan people living with HIV (PLHIV) presenting with diabetic ketoacidosis weeks to months following a switch to dolutegravir (DTG), the Uganda Ministry of Health recommended withholding DTG in both ART naïve and experienced PLHIV with diabetes mellitus (T2DM), as well as 3-monthly blood glucose monitoring for patients with T2DM risk factors. We sought to determine if the risk of T2DM is indeed heightened in nondiabetic ART naïve Ugandan PLHIV over the first 48 weeks on DTG. METHODS: Between January and October 2021, 243 PLHIV without T2DM were initiated on DTG based ART for 48 weeks. Two-hour oral glucose tolerance tests (2-h OGTT) were performed at baseline, 12, and 36 weeks; fasting blood glucose (FBG) was measured at 24 and 48 weeks. The primary outcome was the incidence of T2DM. Secondary outcomes included: incidence of pre-Diabetes Mellitus (pre-DM), median change in FBG from baseline to week 48 and 2-h blood glucose (2hBG) from baseline to week 36. Linear regression models were used to determine adjusted differences in FBG and 2hBG from baseline to weeks 48 and 36 respectively. RESULTS: The incidence of T2DM was 4 cases per 1000 PY (1/243) and pre-DM, 240 cases per 1000 person years (PY) (54/243). There was a significant increase in FBG from baseline to week 48 [median change from baseline (FBG): 3.6 mg/dl, interquartile range (IQR): − 3.6, 7.2, p-value (p) = 0.005] and significant reduction in 2hBG (2hBG: − 7.26 mg/dl, IQR: − 21.6, 14.4, p = 0.024) at week 36. A high CD4 count and increased waist circumference were associated with 2hBG increase at week 36. CONCLUSION: We demonstrated a low incidence of T2DM in Ugandan ART-naïve patients receiving DTG. We also demonstrated that longitudinal changes in BG were independent of conventional risk factors of T2DM in the first 48 weeks of therapy. Restricting the use of dolutegravir in Ugandan ART naïve patients perceived to be high risk for diabetes mellitus may be unwarranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12981-023-00510-6. BioMed Central 2023-03-13 /pmc/articles/PMC10009965/ /pubmed/36915103 http://dx.doi.org/10.1186/s12981-023-00510-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Mulindwa, Frank
Castelnuovo, Barbara
Brusselaers, Nele
Bollinger, Robert
Rhein, Joshua
Edrisa, Mutebi
Buzibye, Allan
Amutuhaire, Willington
Yendewa, George
Nabaggala, Sarah
Odongpiny, Eva Laker Agnes
Kiguba, Ronald
Nakawooza, Aisha
Dujanga, Simon
Nabwana, Martin
Schwarz, Jean-Marc
Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir
title Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir
title_full Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir
title_fullStr Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir
title_full_unstemmed Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir
title_short Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir
title_sort blood glucose trajectories and incidence of diabetes mellitus in ugandan people living with hiv initiated on dolutegravir
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009965/
https://www.ncbi.nlm.nih.gov/pubmed/36915103
http://dx.doi.org/10.1186/s12981-023-00510-6
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