Ketosis-onset diabetes without islet-associated autoantibodies in a patient with MELAS.

I t has been reported that excessive intake of sugar-containing soft drinks can result in diabetic ketoacidosis or ketosis in obese patients with type 2 diabetes (1). We describe herein soft drink ketosis–onset diabetes in a nonobese patient with mito-chondrial myopathy, lactic acidosis, and stroke-like episodes (MELAS). A 27-year-old Japanese man consulted a local otolaryngeal clinic with a history of tinnitus lasting for 3 weeks and a weight loss of 5 kg in 1 month. He was diagnosed as having sensorineural and apoplectiform deafness and was administered 15 mg prednisolone a day, after which he developed thirst and polydipsia and started drinking 1–3 l of sugar-containing soft drinks a day. After 1 week of prednisolone therapy, he was referred and admitted to our hospital with severe malaise on 6 December 1999. His mother also had diabetes, which was effectively controlled with nateglinide, and sensorineural deafness. The patient' s height was 165 cm, and his weight was 44 kg (BMI 16.2 kg/m 2). He was lucid and of normal mental clarity. His urine was glucose positive, his blood glucose level was 28.2 mmol/l, and his HbA 1c was 8.6%. Blood gas analysis revealed metabolic acidosis (pH = 7.337, base excess = Ϫ3.0 mmol/l, and HCO 3 = 22.8 mmol/l). His urine was strongly positive for ketones, and the serum level of total ketone bodies was 2,232 µmol/l, of 3-hydroxybutylic acid 1,774 µmol/l, and of acetoacetate 458 µmol/l. Serum levels of lactate and pyruvate were 3.0 mmol/l and 167 µmol/l, respectively. The patient was negative for islet-associated autoantibodies, including anti-GAD antibody, anti–IA-2 antibody, islet cell antibody, and insulin autoantibody, and specific HLAs for type 1 diabetes in Japanese people. We diagnosed the patient as having diabetic ketoacidosis and treated him with continuous insulin infusion. After good glycemic control was achieved with intensive insulin therapy (38 U/day), urinary excretion of C-peptide was 8.28 µmol/day, and basal serum level of C-peptide was 0.46 nmol/l. His serum levels of C-peptide responded well to glucagon and arginine challenges, which achieved 1.08 and 2.81 nmol/l, respectively. The maternal transmission of his sensorineural deafness and diabetes prompted us to examine him for mito-chondrial diabetes. A fragment of mito-chondrial DNA containing nucleotide 3243 was amplified by means of a poly-merase chain reaction using a rhodamine-labeled primer and the product was digested with ApaI. The digested product was then separated by acrylamide gel elec-trophoresis and each product was quanti-tated with …