Journal
JOURNAL OF DIABETES AND ITS COMPLICATIONS
Volume 36, Issue 3, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jdiacomp.2021.108111
Keywords
Adverse drug reaction; MELAS; Metformin; MIDD; Mitochondrial diabetes; Mitochondrial disease
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This study reviewed the diagnosis and management of m.3243A>G-related diabetes and evaluated the risk of metformin use triggering neurological manifestations. The results showed that m.3243A>G-related diabetes is often underdiagnosed, and metformin may trigger neurological manifestations in this condition.
Introduction: m.3243A>G-related disease has multi-systemic manifestations including diabetes mellitus. It is uncertain whether metformin would trigger neurological manifestations of this disease. This study aims to review the diagnosis and management of m.3243A>G-related diabetes genetically confirmed by our laboratory and to evaluate the risk of metformin use triggering neurological manifestations. Methods: Cases with m.3243A>G detected between 2009 and 2020 were reviewed. Cases with diabetes mellitus were included. Cases with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) before diabetes onset were excluded. Odds ratio was calculated for association between metformin use and newly developed neurological manifestations. Results: Sixteen patients were identified. Odds ratio for metformin use was 3.50 [0.37-33.0; p = 0.3287]. One illustrative case with clear causal relationship between metformin use and neurological manifestations was described in detail. Conclusion: m.3243A>G-related diabetes mellitus is underdiagnosed. Red flags including positive family history, short stature, low body weight and hearing loss are often overlooked. Early diagnosis allows regular systemic assessment. In the era of precision medicine and novel therapies, it is prudent to avoid metformin as it could trigger neurological manifestations in this condition. Coenzyme Q10, DPP-IV inhibitors, SGLT2 inhibitors and GLP-1 receptor agonists may be considered.
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