Diabetes and tuberculosis: a systematic review and meta-analyis of mendelian randomization evidence

Abstract Background Tuberculosis (TB) and diabetes mellitus (DM) are global health challenges, each imposing significant morbidity and mortality. Observational studies suggest an increased TB risk in individuals with DM, yet causal relationships remain unclear due to potential confounding factors. M...

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Main Authors: Ivaan Pitua, Raafidha Raizudheen, Mark Muyanja, Joseph Nyero, Morrish Okello Obol
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Diabetology & Metabolic Syndrome
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Online Access:https://doi.org/10.1186/s13098-025-01615-w
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author Ivaan Pitua
Raafidha Raizudheen
Mark Muyanja
Joseph Nyero
Morrish Okello Obol
author_facet Ivaan Pitua
Raafidha Raizudheen
Mark Muyanja
Joseph Nyero
Morrish Okello Obol
author_sort Ivaan Pitua
collection DOAJ
description Abstract Background Tuberculosis (TB) and diabetes mellitus (DM) are global health challenges, each imposing significant morbidity and mortality. Observational studies suggest an increased TB risk in individuals with DM, yet causal relationships remain unclear due to potential confounding factors. Mendelian randomization (MR) offers a method to assess causality by leveraging genetic variants as instrumental variables, mitigating biases from confounding and reverse causation. This systematic review aimed to consolidate existing MR evidence on the causal link between DM (types 1 and 2) and TB. Methods A comprehensive search was conducted in PubMed, Embase, Google Scholar, and Web of Science, identifying MR studies investigating the causal association between DM and TB. Studies were screened based on pre-specified inclusion criteria and assessed for quality using the STROBE-MR guidelines. Data extraction focused on study characteristics, MR methodology, and causal effect estimates. A meta-analysis was conducted estimate the pooled odds ratios for association between T2DM and TB. Results Four MR studies met the inclusion criteria, spanning East Asian and European populations. Findings indicated a consistent causal relationship between DM (particularly type 2 diabetes) and increased TB risk, with odds ratios (OR) ranging from 1.07 to 1.24 (p < 0.05). The pooled odds ratio (OR) was 1.2172 (95% CI: 1.1101–1.3347, p < 0.0001), indicating a significant positive association between T2DM and TB. One study identified pleiotropic effects, suggesting potential genetic overlap in DM and TB susceptibility. No reverse causal association was observed, indicating that TB does not increase the risk of DM. Conclusion This review highlights a causal association between DM and TB, emphasizing the need for integrated screening and management of DM within TB control programs, particularly in high-burden regions. Future MR studies should include diverse populations to enhance generalizability and explore genetic mechanisms underlying this association.
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spelling doaj-art-cec0a176beaf4676b8ef202f49d91aa22025-02-09T12:48:19ZengBMCDiabetology & Metabolic Syndrome1758-59962025-02-011711910.1186/s13098-025-01615-wDiabetes and tuberculosis: a systematic review and meta-analyis of mendelian randomization evidenceIvaan Pitua0Raafidha Raizudheen1Mark Muyanja2Joseph Nyero3Morrish Okello Obol4Makerere University College of Health SciencesMakerere University College of Health SciencesMakerere University College of Health SciencesThe Hebrew University-Hadassah Braun School of Public Health and Community MedicineFaculty of Medicine, Gulu UniversityAbstract Background Tuberculosis (TB) and diabetes mellitus (DM) are global health challenges, each imposing significant morbidity and mortality. Observational studies suggest an increased TB risk in individuals with DM, yet causal relationships remain unclear due to potential confounding factors. Mendelian randomization (MR) offers a method to assess causality by leveraging genetic variants as instrumental variables, mitigating biases from confounding and reverse causation. This systematic review aimed to consolidate existing MR evidence on the causal link between DM (types 1 and 2) and TB. Methods A comprehensive search was conducted in PubMed, Embase, Google Scholar, and Web of Science, identifying MR studies investigating the causal association between DM and TB. Studies were screened based on pre-specified inclusion criteria and assessed for quality using the STROBE-MR guidelines. Data extraction focused on study characteristics, MR methodology, and causal effect estimates. A meta-analysis was conducted estimate the pooled odds ratios for association between T2DM and TB. Results Four MR studies met the inclusion criteria, spanning East Asian and European populations. Findings indicated a consistent causal relationship between DM (particularly type 2 diabetes) and increased TB risk, with odds ratios (OR) ranging from 1.07 to 1.24 (p < 0.05). The pooled odds ratio (OR) was 1.2172 (95% CI: 1.1101–1.3347, p < 0.0001), indicating a significant positive association between T2DM and TB. One study identified pleiotropic effects, suggesting potential genetic overlap in DM and TB susceptibility. No reverse causal association was observed, indicating that TB does not increase the risk of DM. Conclusion This review highlights a causal association between DM and TB, emphasizing the need for integrated screening and management of DM within TB control programs, particularly in high-burden regions. Future MR studies should include diverse populations to enhance generalizability and explore genetic mechanisms underlying this association.https://doi.org/10.1186/s13098-025-01615-wTuberculosisDiabetes MellitusMendelian randomization
spellingShingle Ivaan Pitua
Raafidha Raizudheen
Mark Muyanja
Joseph Nyero
Morrish Okello Obol
Diabetes and tuberculosis: a systematic review and meta-analyis of mendelian randomization evidence
Diabetology & Metabolic Syndrome
Tuberculosis
Diabetes Mellitus
Mendelian randomization
title Diabetes and tuberculosis: a systematic review and meta-analyis of mendelian randomization evidence
title_full Diabetes and tuberculosis: a systematic review and meta-analyis of mendelian randomization evidence
title_fullStr Diabetes and tuberculosis: a systematic review and meta-analyis of mendelian randomization evidence
title_full_unstemmed Diabetes and tuberculosis: a systematic review and meta-analyis of mendelian randomization evidence
title_short Diabetes and tuberculosis: a systematic review and meta-analyis of mendelian randomization evidence
title_sort diabetes and tuberculosis a systematic review and meta analyis of mendelian randomization evidence
topic Tuberculosis
Diabetes Mellitus
Mendelian randomization
url https://doi.org/10.1186/s13098-025-01615-w
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