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Imeglimin‐mediated glycemic control in maternally inherited deafness and diabetes

by Okano, Kosuke , Aiba, Saki , Ohtani, Ryohei , Koshizaka, Masaya , Kuroda, Yuta , Kasahara, Keisuke , Iga, Ryo , Baba, Yusuke , Maezawa, Yoshiro , Watanabe, Suzuka , Inaba, Yosuke , Hirayama, Kiichi , Ito, Chiho , Yokote, Koutaro , Kanayama, Takuma , Ishibashi, Ryoichi

in Acidosis / Ammonia / Blood glucose / Blood levels / Case Report / Citrulline / Creatinine / Deafness / Diabetes / Diabetes mellitus / Fatty acids / Glucagon / Glucose / Glucose transporter / Heart failure / Histamine / Imeglimin / Insulin / Insulin secretion / Maternally inherited diabetes and deafness / Metabolism / Metabolites / Metabolome / Mutation / Na+/glucose cotransporter / Peptides / Secretion / Sulfonylurea / Trends

2023

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Imeglimin‐mediated glycemic control in maternally inherited deafness and diabetes

2023

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Imeglimin‐mediated glycemic control in maternally inherited deafness and diabetes

2023

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Journal Article

Imeglimin‐mediated glycemic control in maternally inherited deafness and diabetes

Okano, Kosuke,

Aiba, Saki,

Ohtani, Ryohei,

Koshizaka, Masaya,

Kuroda, Yuta,

Kasahara, Keisuke,

Iga, Ryo,

Baba, Yusuke,

Maezawa, Yoshiro,

Watanabe, Suzuka,

Inaba, Yosuke,

Hirayama, Kiichi,

Ito, Chiho,

Yokote, Koutaro,

Kanayama, Takuma,

Ishibashi, Ryoichi

2023

Overview

Mitochondrial dysfunction causes maternally inherited deafness and diabetes (MIDD). Herein, we report improved glycemic control in a 47‐year‐old Japanese woman with MIDD using imeglimin without major adverse effects. Biochemical tests and metabolome analysis were performed before and after imeglimin administration. Blood glucose level fluctuations were determined. Sulfonylureas, dipeptidyl peptidase‐4 inhibitors (DPP4is), and sodium glucose transporter‐2 inhibitors (SGLT2i) were administered to evaluate the efficacy of their combination with imeglimin. Imeglimin decreased the HbA1c and ammonia levels and increased the time‐in‐range, C‐peptide reactivity, and glucagon level. Elevated citrulline and histamine levels were decreased by imeglimin. The hypoglycemic effect was not enhanced by imeglimin when combined with sulfonylurea or DPP4i, but the blood glucose level was improved when combined with SGLT2i. Imeglimin improved glucose concentration‐dependent insulin secretion and maximized the insulin secretory capacity by improving mitochondrial function and glutamine metabolism and urea circuit abnormalities by promoting glucagon secretion. Imeglimin could improve glycemic control in MIDD. We studied the effect of imeglimin in a patient with maternally inherited diabetes and deafness (MIDD). Imeglimin potentially improves glucose concentration‐dependent insulin secretion and metabolism in MIDD. Imeglimin shows potential as a new treatment for MIDD.

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Publisher

John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley

Subject

/ Ammonia