Systematic and meta-analysis of Mycobacterium avium subsp. paratuberculosis related type 1 and type 2 diabetes mellitus

Abstract

Global increase in diabetes (DM) prevalence necessitated the need to establish the association between DM and environmental triggers including MAP (Mycobacterium avium subsp. paratuberculosis) that have been postulated to play a role in DM etiopathology for effective management. The present investigation aimed to assess the odds ratio (OR) presenting the association between MAP and DM. MAP-related DM studies were systematically retrieved from 6 databases until 31 September 2021 according to PRISMA principles for data abstraction. The abstracted dataset was fitted to the fixed-effects (FE) and random-effects (RE) models using the Mantel-Haenszel approach. Sixteen studies involving 2072 participants (1152 DM patients (957 type 1 diabetes mellitus (T1DM) & 195 type 2 diabetes mellitus (T2DM)) and 920 healthy controls) met the inclusion criteria. Results revealed a significant association between anti-MAP antibodies (abs) seroprevalence and T1DM (FE: OR 7.47, 95% CI 5.50-10.14, p value < 0.0001; RE: OR 7.92, 95% CI 4.39-14.31, p < 0.0001) and MAP DNA with T1DM (FE: OR 4.70 (95% CI 3.10-7.13, p value < 0.0001), RE: OR 3.90 (95% CI 0.93-16.38, p value = 0.06)). Both anti-MAP abs and MAP DNA based meta-analyses had medium heterogeneity (I² = 47.2-61.0%). Meanwhile, no significant association between MAP and T2DM (FE: OR 1.13, 95% CI 0.54-2.37, p value = 0.74; RE: OR 1.19; 95% CI 0.34-4.12, p value = 0.69), its OR magnitude exceeded 1 and prediction interval (0.09-15.29) suggest possibility of association between the duo in the future. The leave-one-out sensitivity analysis depicts a robust meta-analysis in all cases. In conclusion, the study manifests a positive association between MAP and T1DM, highlighting that MAP prevention and environmental control would indubitably revolutionize T1DM management. Also, its projects possible link between MAP and T2DM as more data becomes available. However, it remains elusive whether MAP triggers T1/T2DM or a mere comorbidity in T1/T2DM. Epidemiological activities to fill the global/regional data gaps on MAP-related T1DM and T2DM are advocated in order to assess the burden of MAP-related DM and improve their clinical management.