Early insulin resistance predicts weight gain and waist circumference increase in first-episode psychosis – A one year follow-up study

Abstract

First-episode psychosis (FEP) is associated with weight gain during the first year of treatment, and risk of abdominal obesity is particularly increased. To identify early risk markers of weight gain and abdominal obesity, we investigated baseline metabolic differences in 60 FEP patients and 27 controls, and longitudinal changes during the first year of treatment in patients. Compared to controls at baseline, patients had higher low-density lipoprotein, triglyceride and apolipoprotein B levels, and lower levels of high-density lipoprotein and apolipoprotein A-I but no difference in body mass index or waist circumference. At 12-month follow-up, 60.6% of patients were overweight or obese and 58.8% had abdominal obesity. No significant increase during follow-up was seen in markers of glucose and lipid metabolism or blood pressure, but increase in C-reactive protein between baseline and 12-month follow-up was statistically significant. Weight increase was predicted by baseline insulin resistance and olanzapine use, while increase in waist circumference was predicted by baseline insulin resistance only. In conclusion, insulin resistance may be an early marker of increased vulnerability to weight gain and abdominal obesity in young adults with FEP. Olanzapine should be avoided as a first-line treatment in FEP due to the substantial weight increase it causes. In addition, the increase in the prevalence of overweight and abdominal obesity was accompanied by the emergence of low-grade systemic inflammation.

Introduction

Psychotic disorders are associated with increased risk of obesity, metabolic syndrome and type 2 diabetes (Mitchell et al., 2013). It is unclear to what extent this is related to poor nutrition, sedentary lifestyle, and antipsychotic treatment, or whether some of the alterations might actually reflect core pathophysiology of these disorders (Harris et al., 2013). First reports concerning abnormalities of glucose metabolism in psychosis appeared already before the widespread use of antipsychotics, and drug-naïve first-episode psychosis (FEP) patients show impaired glucose tolerance and insulin resistance (Harris et al., 2013, Spelman et al., 2007, Kirkpatrick et al., 2012). Based on a meta-analysis, drug-naïve FEP patients may also have higher waist–hip ratio and more intra-abdominal fat compared to healthy controls but no difference in body mass index (BMI) (Foley and Morley, 2011).

During antipsychotic treatment, weight increases markedly during the first weeks and months, and most of the total increase takes place during the first year of treatment (Perez-Iglesias et al., 2014). Most antipsychotics cause weight gain with differing propensity (Foley and Morley, 2011, Leucht et al., 2013). Results on pre-treatment lipid abnormalities remain contradictory, while most antipsychotics cause elevated total and low-density lipoprotein (LDL) cholesterol and triglyceride levels and reduced high-density lipoprotein (HDL) cholesterol levels (Foley and Morley, 2011). Abdominal obesity is the hallmark of dysfunctional adipose tissue (Despres and Lemieux, 2006), and people with schizophrenia are particularly vulnerable to this metabolically unfavorable form of obesity (Saarni et al., 2009).

Weight gain is one of the major reasons for problems in treatment adherence (Velligan et al., 2009). The risk of young people to medication induced somatic comorbidities is especially high and should be minimized (Mitchell et al., 2013). Thus, it is of great interest to identify risk factors for weight gain and increased waist circumference specifically in people with recent onset psychosis. Previous studies on FEP patients suggest that risk factors for clinically significant weight increase during treatment include lower BMI, younger age, negative symptoms, and olanzapine treatment, but predictors have not been consistent across studies (Strassnig et al., 2007, Perez-Iglesias et al., 2014) and are inadequate to inform clinical decision on treatment. Also inflammation, which is common in FEP (Miller et al., 2011), may contribute to antipsychotic-induced weight gain (Song et al., 2013). Low-grade inflammation has been associated with weight increase in the general population (Vasunilashorn, 2013). It remains unclear whether the risk factors of weight gain and abdominal obesity in early psychosis differ.

The aim of this study was to identify baseline risk factors for weight gain and waist circumference increase at 12-month follow-up among FEP patients comparing them with healthy controls.