Rapid Onset of Quetiapine-Induced Diabetic Ketoacidosis in an Elderly Patient

A 72-year-old married Asian male (60 kg, 168 cm, body mass index 21.3 kg/m²) visited our hospital presenting with hyperactivity and irritability. His medical history was notable for alcohol use for 50 years, abuse for 4 years (ethanol equivalent, 100-150 g/d) and familial hyperlipidemia, but there was no family or medical history of diabetes mellitus or glucose intolerance. He stopped drinking alcohol for 6 months. On his first visit to our hospital, he was euphoric and confabulatory. His mini-mental state examination score was 14/30 [4]. His short-term memory and time and place orientation were markedly impaired. Spatial cognition and judgment were relatively preserved. Laboratory test results including those for glucose (132 mg/dl, at 2 h after lunch) and bicarbonate, renal function, and hepatic enzymes were within normal ranges. MRI demonstrated moderate diffuse brain atrophy without any ischemic changes. He was diagnosed as having dementia with Korsakoff findings. Tiapride at 50 mg/day was initiated and gradually increased to 200 mg/day, which was not efficacious. Subsequently, low-dose quetiapine at 50 mg/day was added.

By day 8, both his sleep and behavior had improved, but by day 11, he was somnolent although he had not drunk during this time. On day 15, he was hospitalized. He could be roused, but was unable to answer any questions. Serum chemistry revealed an osmolality of 410 mOsm/kg due to hyperglycemia at 973 mg/dl. The serum ketone level was higher than 40 mg/dl. An arterial blood gas analysis showed metabolic acidosis: pH 7.294; HCO₃ 16.7 mEq/l; and base excess -8.8 mEq/l. His hyperosmolar state and diabetic ketoacidosis were managed with fluids (2500 ml/d, for 3 days) and an intravenously administered insulin (50-25 i. u./d) for 5 days. Subsequently, he was managed with intermittent subcutaneous insulin injections for 2 weeks (34-20 i. u./d). His treatment regimen was then switched to glibenclamide at 1.25 mg/d, and his glucose level showed good control one week after the switch. His agitation was controlled using 3 mg/d haloperidol and 400 mg/d valproate, which are the maximum doses. After 4 months, his agitation was well controlled by only 300 mg/d valproate and then he was subsequently discharged. Soon after, glibenclamide was stopped and his glucose level showed good control.

Although cases of new-onset DM and DKA have been reported in patients treated with quetiapine, the presence of risk factors, such as obesity, the excessive intake of carbonated drinks, prior carbohydrate intolerance and a family history of diabetes mellitus, was considered important [1] [2] [5] [7] [8] [9] [10]. This patient, however, had none of these risk factors. Also of note is the rapid onset of life-threatening hyperglycemia and acidosis while on a low dose of quetiapine.

It should also be noted that alcohol consumption can contribute to ketoacidosis, particularly in poorly nourished patients with emesis. A mixed ketoacidosis may occur with alcohol intake, particularly in the setting of insufficient bioavailable insulin. This patient stopped drinking when medication started. Howard et al. reported that heavy alcohol consumption may be associated with the increased incidence of diabetes mellitus [6]. Thus a history of heavy alcohol consumption may be a risk factor of new-onset DM adverse effect of quetiapine.

Koller et al. reported two cases of newly diagnosed hyperglycemia after using quetiapine for demented patients [8]. The treatment at low doses of atypical antipsychotics used for dementia management may lead to diabetes more readily in the geriatric population because of a decreased muscle mass followed by a decrease in glucose utilization and age-related islet cell decompensation. In this case, the early detection and treatment of DKA had a satisfactory outcome. Recently the FDA issued a warning that olanzapine increases the possibility of cerebrovascular adverse events in elderly patients and that it had not approved for the treatment of BPSD [3]. Therefore, physicians should be aware of the possibility of life-threatening adverse effects when we prescribe quetiapine for BPSD in demented patients.

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