Background Several families have been described in which a mutationof mitochondrial DNA, the substitution of guanine for adenine(A-to-G) at position 3243 of leucine transfer RNA, is associatedwith diabetes mellitus and deafness. The prevalence, clinicalfeatures, and pathophysiology of diabetes with this mutationare largely undefined.
Methods We studied 55 patients with insulin-dependent diabetesmellitus (IDDM) and a family history of diabetes (group 1),85 patients with IDDM and no family history of diabetes (group2), 100 patients with non-insulin-dependent diabetes mellitus(NIDDM) and a family history of diabetes (group 3), and 5 patientswith diabetes and deafness (group 4) for the mutation. We alsostudied the prevalence and characteristics of diabetes in 39patients with a syndrome consisting of mitochondrial myopathy,encephalopathy, lactic acidosis, and stroke-like episodes whowere known to have the mutation and 127 of their relatives (group5).
Results We identified 16 unrelated patients with diabetes associatedwith the A-to-G mutation: 3 patients from group 1 (6 percent),2 patients from group 3 (2 percent), 3 patients from group 4(60 percent), and 8 patients from group 5 (21 percent). We alsoidentified 16 additional subjects who had diabetes and the mutationamong 42 relatives of the patients with diabetes and the mutationin groups 1, 2, 3, and 4 and 20 affected subjects among the127 relatives of the patients in group 5. Diabetes cosegregatedwith the mutation in a fashion consistent with maternal transmission,was frequently (in 61 percent of cases) associated with sensoryhearing loss, and was generally accompanied by impaired insulinsecretion.
Conclusions Diabetes mellitus associated with the A-to-G mutationat position 3243 of mitochondrial leucine transfer RNA representsa subtype of diabetes found in both patients with IDDM and patientswith NIDDM in Japan.
Source Information
From the Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo (T. Kadowaki, Y.M., K.T., H.S., T.H., Y.Y.); the Institute for Diabetes Care and Research, Asahi Life Foundation, Tokyo (H.K., R.H., Y.A.); the Division of Ultrastructural Research, National Institute of Neuroscience, Kodaira (R.S., Y.G., I.N.); Chiba Children's Hospital, Chiba (Y.T.); the Department of Endocrinology and Metabolism, Jichi Medical School, Minamikawachi (T.A.); Saiseikai Central Hospital, Tokyo (Y.S., K.M.); the First Department of Internal Medicine, Osaka University Medical School, Osaka (R.K., T. Kamada); and the National Institute of Genetics, Mishima (S.H.) -- all in Japan.
Address reprint requests to Dr. T. Kadowaki at the Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
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