Mitochondrial diabetes associated with a tRNA^Leu(UUR) mutation at position 3271: Over a 15-year follow-up observation

A 54-year-old man had mitochondrial diabetes associated with a tRNA ^Leu(UUR) mutation at position 3271. The patient's glycemic control deteriorated transiently when he became positive for glutamic acid decarboxylase (GAD) antibodies, then improved as he became negative for GAD antibodies. Only seven cases of mitochondrial diabetes with GAD antibodies have so far been reported in the literature, and no other patient has reverted to GAD negativity with insulin independence. The phenomenon observed in this case is so rare that it is important to understand the associations between GAD antibodies, mitochondrial dysfunction and diabetes. Six years later, the patient's insulin secretion gradually decreased. Therefore, we initiated treatment with sitagliptin (dipeptidyl peptidase-4 inhibitor) at a dose of 50 mg/day, then increased the dose up to 100 mg/day. After nine months, the patient's glycemic control improved with increased early insulin secretion and suppression of postprandial hyperglycemia. To our knowledge, this is the first case report in the literature indicating that a DPP4 inhibitor is effective for the treatment of mitochondrial diabetes associated with ^{tRNA Leu (UUR)} mutations at position 3271. Hence, this case report provides important insight into a rare phenomenon. The patient's family history showed a strong inheritance of type 2 diabetes but no hearing loss. This provides a hint to understanding the different roles of 3243 and 3271 mitochondrial DNA mutations in the characteristics of mitochondrial diabetes.