Abstract:

CONTEXT: Mitochondrial diabetes is a rare form of diabetes mellitus accounting for up to 1% of all diabetes. Pyruvate therapy has been reported to be a potential therapeutic choice for patients with mitochondrial diseases. CASE DESCRIPTION: Water-based sodium pyruvate solutions (0.5 g/kg, thrice daily) were administrated orally to a 32-year-old Japanese male with mitochondrial diabetes and myopathy caused by m.14709T>C mutation. At the age of 20 years, he was diagnosed with diabetes mellitus and started insulin therapy. He tested negative for islet cell and glutamic decarboxylase antibodies. To evaluate favorable therapeutic improvements, we measured the lactate and pyruvate levels in plasma and cerebrospinal fluid; urinary C-peptide, glycated hemoglobin, and glycoalbumin levels; and total daily insulin dose (TDD). The patient experienced no side effects such as diarrhea because of pyruvate therapy. His urinary C-peptide level improved from 4.3 to 17.2 μg/d after 1 day and to 30.2 μg/d after 6 months of pyruvate therapy. TDD decreased from 33 to 20 U/d after 6 months of pyruvate therapy, but the lactate levels of plasma and cerebrospinal fluid and the lactate/pyruvate ratio did not change.
CONCLUSIONS: Sodium pyruvate improved insulin secretion and resulted in decreased TDD in a patient with mitochondrial diabetes. Pyruvate therapy may be a potential therapeutic choice for patients with mitochondrial diabetes. Clinical trials involving a larger number of patients and long-term evaluation of the therapy are necessary to clarify the efficacy of pyruvate therapy.

日本語要旨:

ミトコンドリア遺伝子異常による糖尿病患者に対して、ピルビン酸塩を経口投与(0.5/kg/day)し治療効果の評価を行った。患者は32歳　日本人男性で、20歳の時にミトコンドリア異常性糖尿病と診断された。治療効果は血液、髄液中の乳酸、ピルビン酸、Cペプチド、糖化ヘモグロビン、糖化アルブミン、そして1日の総インスリン投与量(TDD)で評価した。 治療開始1日後、Cペプチドは4.3から17.2ug/dayに増加し、6か月後では30.2ug/dayまで増加し、TDDは33から20units/dayまで減量することができた。しかし、血中、髄液中ともに乳酸/ピルビン酸比の改善は認められなかった。このようにミトコンドリア異常による糖尿病患者に対して、ピルビン酸は有用な治療の可能性が見込まれるが、さらに多くの患者で長期にわたる臨床試験による評価が必要となるだろう。