Insulin Resistance and Increased Leptin Concentrations in Noncompliant Schizophrenia Patients but Not in Antipsychotic-Naive First-Episode Schizophrenia Patients

Belén Arranz, M.D., Ph.D.; Pilar Rosel, M.D., Ph.D.; Nicolas Ramírez, M.D., Ph.D.; Rosa Dueñas, M.D.; Paloma Fernández, M.D.; Jose María Sanchez, M.D.;Miguel Angel Navarro, M.D., Ph.D.; and Luis San, M.D., Ph.D.

Background: The onset of diabetes and impaired glucose metabolism among schizophrenic patients has been the topic of numerous recently published articles, with research implicating weight gain, the use of antipsychotic medication, history of diabetes mellitus in family members, and the diagnosis of schizophrenia itself as risk factors. Therefore, it was the aim of this study to determine the glucose metabolism parameters in noncompliant unmedicated schizophrenic patients (antipsychotic-free) and first-episode antipsychotic-naive schizophrenic patients to investigate whether there is a preexisting impairment of glucose metabolism in never-medicated schizophrenic patients.

Method: Plasma glucose, insulin, C-peptide, and leptin concentrations were determined in 50 antipsychotic-free and 50 antipsychotic-naive DSM-IV schizophrenia patients and 50 healthy control subjects. Insulin resistance was calculated through the homeostatic model assessment (HOMA). The General Linear Model (univariate) procedure was used to perform analysis of covariance. Patients were recruited from July 2001 to December 2002.

Results: Antipsychotic-free patients showed significantly increased insulin (p = .001) and C-peptide (p = .02) concentrations and a significantly higher degree of insulin resistance (p = .003), as measured with the HOMA index, in comparison with the antipsychotic-naive patients and the control group. Significantly increased leptin concentrations (p = .000) were also noted in the antipsychotic-free patients and were attributed to the effects of body mass index (p = .000) and sex (p = .000).

Conclusions: The results reported in this study suggest the effect of previous antipsychotic treatment on glucose metabolism parameters and weight-related hormones such as leptin, while ruling out a preexisting impairment of glucose metabolism in never-medicated first-episode schizophrenic patients.

(J Clin Psychiatry 2004;65:1335-1342)

Received Sept. 15, 2003; accepted March 15, 2004. From Benito Menni, Mental Health Care Institute, Hospital de Granollers (Drs. Arranz, Ramírez, Dueñas, Fernández, Sanchez, and San) and the Hormone Unit, Department of Clinical Chemistry, Ciutat Sanitaria i Universitaria de Bellvitge (Drs. Rosel and Navarro), Barcelona, Spain.

This study was performed with the support of Fundació La Marató de TV3, Barcelona, Spain (grant 01/5330), and Lilly Pharmaceuticals, Madrid, Spain (grant F1D-XB-O07). Eli Lilly Spain provided financial support that partially covered the cost of the biochemical reagents and commercial RIA kits.

Experimental design, patient recruitment, and statistical analyses were performed by the authors. Biochemical determinations were performed in an independent laboratory (Department of Clinical Chemistry, Ciutat Sanitaria i Universitaria de Bellvitge, Barcelona, Spain) by Drs. Arranz and Rosel. Statistical analysis was performed by Drs. Ramírez and Arranz. All authors participated in the discussion of the results obtained.

The authors thank all members of the nursing staff from Benito Menni, Mental Health Care Institute for their valuable help.

Corresponding author and reprints: Belén Arranz, M.D., Ph.D., Department of Psychiatry, Hospital de Granollers, Benito Menni, CASM, Avda. Francesc Ribas s/n, 08400 Granollers, Barcelona, Spain(e-mail: 24439bam@comb.es).