Olanzapine-induced severe hyperglycemia was completely reversed by the restoration of insulin secretion after switching to aripiprazole and initiating insulin therapy

Abstract

A 54-year-old Japanese man who had received a diagnosis of schizophrenia and been treated with olanzapine for nearly 16 months consulted our department because of severe hyperglycemia (535 mg/dL). The use of antipsychotics, switching the patient from olanzapine to aripiprazole, and 7 weeks of insulin therapy resulted in a decrease in the patient's postprandial blood glucose levels and an increase in his postprandial C-peptide levels (442 mg/dL to 106 mg/dL and 1.72 ng/mL to 4.94 ng/mL, respectively) as well as an improvement in his pre-prandial levels (250 mg/dL to 85 mg/dL and 1.00 ng/mL to 1.69 ng/mL, respectively) with almost no change in the 24-hour urinary excretion of C-peptide. These results suggested that an insufficiency of insulin secretion, not insulin resistance, was associated with the patient's severe hyperglycemia, and that olanzapine-induced pancreatic β-cell impairment might be reversible if the hyperglycemia is diagnosed and treated sufficiently early. When prescribing second-generation antipsychotics such as olanzapine, clinicians should take the level of insulin into account in addition to monitoring serum glucose levels.

Antipsychotic olanzapine-induced misfolding of proinsulin in the endoplasmic reticulum accounts for atypical development of diabetes

“…Nonetheless, olanzapine-induced diabetes includes atypical cases, as follows. First, while it usually takes years to develop diabetes via insulin resistance, olanzapine-induced diabetes occurs within 6 months after commencing treatment ( Kinoshita et al, 2014 ; Nakamura et al, 2014 ; Nakamura and Nagamine, 2010 ). Second, discontinuing olanzapine treatment cures diabetes even after the level of HbA1c (a marker for blood glucose level) reaches >10%, a ratio which normally representing an irreversible level in patients with type I or type II diabetes ( Nakamura et al, 2014 ; Nakamura and Nagamine, 2010 ; Nathan et al, 2009 ; Young et al, 2012 ).…”

“…First, while it usually takes years to develop diabetes via insulin resistance, olanzapine-induced diabetes occurs within 6 months after commencing treatment ( Kinoshita et al, 2014 ; Nakamura et al, 2014 ; Nakamura and Nagamine, 2010 ). Second, discontinuing olanzapine treatment cures diabetes even after the level of HbA1c (a marker for blood glucose level) reaches >10%, a ratio which normally representing an irreversible level in patients with type I or type II diabetes ( Nakamura et al, 2014 ; Nakamura and Nagamine, 2010 ; Nathan et al, 2009 ; Young et al, 2012 ). Moreover, diabetic ketoacidosis, which is caused by insulin hyposecretion, often occurs in patients with type I diabetes, but also rapidly (within 6 months after treatment with olanzapine) affects patients with no diabetic symptoms before medication ( Kinoshita et al, 2014 ; Tsuchiyama et al, 2004 ).…”

Hyperbaric oxygen exposure alleviate metabolic side-effects of olanzapine treatment and is associated with Langerhans islet proliferation in rats

“…The main findings in the current work are that olanzapine treated rats actually lose weight, but continue to exhibit metabolic dysregulation (fasting glucose and insulin levels) which appear to be mitigated by hyperbaric oxygen treatment. A study stated that OLZ is associated with high blood sugar levels which may be reversible after discontinuation of treatment [21,45,46]. It has been hypothesized that OLZ can decrease the responsiveness of the pancreatic β-cells or even induce pancreatic cell apoptosis in animal models or in vitro [11,22,47].…”

Does olanzapine impair pancreatic beta-cell function directly?

“…Chronic schizophrenic patients treated with olanzapine showed an increase in the level of remnant-like lipoprotein that was not related to obesity and insulin resistance, suggesting that olanzapine decreases insulin secretion [4]. Sporadic cases of rapid-onset diabetes induced by the use of olanzapine have been reported in the literature [5][6] [7]. In these cases, the patients were negative for anti-glutamic acid decarboxylase (anti-GAD) antibodies, which indicate type 1 diabetes, and the discontinuation of olanzapine therapy and a careful insulin replacement treatment regimen reversed their diabetes.…”