Tohoku J. Exp. Med., 2016 April, 238(4)

Early Onset of Diabetes Mellitus Accelerates Cognitive Decline in Japanese Patients with Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes

TAKAAKI MURAKAMI,¹ YUYA SHINOTO,² SHIN YONEMITSU,¹ SEIJI MURO,¹ SHOGO OKI,¹ YASUTOSHI KOGA,³ YU-ICHI GOTO⁴ and DAITA KANEDA⁵

¹Department of Diabetes and Endocrinology, Osaka Red Cross Hospital, Osaka, Osaka, Japan
²Department of Neurology, Osaka Red Cross Hospital, Osaka, Osaka, Japan
³Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Fukuoka, Japan
⁴Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
⁵Department of Neurology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan

Approximately 80% of patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) carry the A3243G mutation in the mitochondrial tRNALeu (UUR) gene. Conversely, this mutation has also been identified as one of the most prevalent genetic abnormalities in patients with diabetes mellitus. Mitochondrial diabetes mellitus complicated with MELAS is relatively common, and 12.5% of patients with the A3243G mutation develop MELAS after being diagnosed with diabetes mellitus. However, the clinical impact of diabetes mellitus in MELAS patients remains unclear. Therefore, we retrospectively studied 14 Japanese MELAS patients with the A3243G mutation: three men and eleven women, with the mean age of 48.0 (± 15.4) years. Eight patients had been diagnosed with diabetes mellitus prior to the diagnosis of mitochondrial disease, and all of them were treated with insulin. The other six included four patients with concurrent diagnosis of diabetes and mitochondrial disease, one patient diagnosed with diabetes after the diagnosis of mitochondrial disease, and one patient without developing diabetes currently. We thus compared the patients' characteristics between those with and without early onset of diabetes mellitus. Cognitive decline (75.0% vs. 0%; p = 0.03) and poor glycemic control with severe hypoglycemic events (75.0% vs. 16.7%; p = 0.05) were more common in MELAS patients with a prior diagnosis of diabetes than in those without the prior diagnosis of diabetes. Our data suggest that the latent progress of cognitive decline is accelerated because of early onset of diabetes mellitus in MELAS patients.

keywords —— cognitive decline; hypoglycemia; MELAS; mitochondrial diabetes mellitus; A3243G mutation

© 2016 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2016, 238, 311-316

Correspondence: Takaaki Murakami, M.D., Department of Diabetes and Endocrinology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka, Osaka 543-0027, Japan.

e-mail: t.murakami@osaka-med.jrc.or.jp