Janssen - Glucose Regulation/Risp/Olanz
Condition: Schizophrenia; Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2; Schizophrenia
Study type: Interventional

Summary: 
      Abnormalities in peripheral glucose regulation and type 2 diabetes can occur more commonly in
      individuals with schizophrenia than in healthy subjects or in other psychiatric conditions.
      Antipsychotic treatment may contribute significantly to abnormalities in glucose regulation.
      Hyperglycemia can contribute to long-term cardiovascular disease risk that may already be
      increased in patients with schizophrenia due to higher rates of smoking, sedentary life
      style, obesity and under-treated hypertension and dyslipidemia. This project will
      characterize the effects on glucose control of the two most commonly prescribed newer
      antipsychotic medications, risperidone and olanzapine, in patients with schizophrenia.

      This proposal specifically hypothesizes that olanzapine treatment will be associated with
      decreases in insulin sensitivity (SI), without effects on insulin secretion.
      Treatment-related effects on glucose effectiveness (SG) will be explored.
    

Detailed description: 
      This proposal aims to use a well-characterized procedure, the modified Frequently Sampled
      Intravenous Glucose Tolerance Test (FSIGTT), to characterize the glucoregulatory effects of
      the two most commonly prescribed atypical antipsychotic medications, risperidone and
      olanzapine, in comparison to the conventional antipsychotic haloperidol. Abnormalities in
      peripheral glucose regulation and type 2 diabetes can occur more commonly in individuals with
      schizophrenia than in healthy subjects or in other psychiatric conditions. While
      abnormalities in glucose regulation were first reported in schizophrenia prior to the
      introduction of antipsychotic medications, antipsychotic treatment may contribute
      significantly to abnormalities in glucose regulation.

      Recently, the adverse effect of antipsychotic medications on systemic glucose regulation has
      received increased attention as investigators noted prominent adverse glucoregulatory effects
      associated with certain newer antipsychotic medications. Abnormal glucose regulation and
      new-onset type 2 diabetes have been reported during clozapine and olanzapine treatment.
      Complicating the study of antipsychotic-induced changes in glucose regulation, increased
      adiposity can decrease insulin sensitivity, and antipsychotics can increase adiposity and
      body mass index (BMI). However, abnormal glucose regulation and type 2 diabetes can occur
      during clozapine treatment in the absence of weight gain, suggesting that changes in glucose
      regulation can occur independent of drug-induced increases in BMI. Consistent with this, our
      preliminary studies indicate that important effects of clozapine and olanzapine on glucose
      regulation are not accounted for by differences in BMI. This proposal will compare the
      effects of olanzapine, risperidone and haloperidol on well-defined measures of glucose
      regulation.

      This proposal specifically hypothesizes that olanzapine treatment will be associated with
      decreases in insulin sensitivity (SI), without effects on insulin secretion.
      Treatment-related effects on glucose effectiveness (SG) will be explored.
    

Intervention name(s): Risperidone, Olanzapine
Intervention type(s): Drug
Intervention MeSH terms: Olanzapine; Risperidone
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Schizophrenia; BMI; T2DM