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Schizophrenia Bulletin Advance Access published November 15, 2012

Schizophrenia Bulletin

Diabetes or Prediabetes in Newly Diagnosed Patients With Nonaffective Psychosis?

AHistorical and ContemporaryView

EmilioFernandez-Egea*,1, ClementeGarcia-Rizo2, JorgeZimbron1, and BrianKirkpatrick3

Department of Psychiatry and Behavioural and Clinical Neuroscience Institute, University of Cambridge & Cambridgeshire and
Peterborough NHS Foundation Trust, UK; 2Schizophrenia Unit, Department of Psychiatry, Hospital Clinic, Barcelona, Spain;
Department of Psychiatry, Texas A&M University College of Medicine and Scott & White Healthcare, Temple, TX, US

Conflicting evidence on the risk of type 2 diabetes mellitus (T2DM) in people with schizophrenia prior to antipsychotic treatment has been published in recent years.
In the meta-analysis presented in the current issue,
Mitchell and colleagues1 have compiled all available data
about the prevalence of the metabolic syndrome and its
components in first episode psychosis with or without
antipsychotic medication, concluding that T2DM prevalence was similar between drug-nave patients and the
general population.
However, glucose intolerance exists on a continuum,
and abnormal glucose tolerance less severe than diabetes
may only be identifiable after a glucose challenge. These
less severe degrees of glucose intolerance were reported
in almost all the studies of glucose tolerance that antedated modern antipsychotics. The work of Lorenz2 can
be used as an example, but more than ten other manuscripts were published before 1954. Pooled together, these
old reports showed abnormalities in the post-glucose
challenge blood sugar curve in 16%66% of cases, while
basal metabolic rates were mostly normal. These studies
were largely ignored during the new wave of studies of
diabetes in schizophrenia.
Not surprisingly, recent studies have had similar results.
Abnormalities in glucose tolerance were only seen after a
challenge (such as oral glucose tolerance test or oGTT) in
almost all such recent studies.35 To our knowledge, only
one study has failed to find a statistically significant difference,6 probably due to a small number of schizophrenia patients. Baseline fasting glucose, the same measure
used in this meta-analysis, did not differ between the two
groups. It was also seen in our study,7 which had the largest sample so far of unmedicated first episode psychosis
patients undergoing oGTT. Results mimic the pre-neuroleptic era studies, with approximately 20% of patients

exhibiting abnormal glucose tolerance prior to antipsychotic treatment, above what is expected in the general
We and others have proposed that schizophrenia is associated with accelerated aging.8 The replicated abnormality
in the oGTT, found in patients groups that are typically in
their late twenties, provides support for this concept.
This evidence does not contradict the strong evidence
that health habits, access to care, and antipsychotic drugs
increase the risk of T2DM in people with schizophrenia
and related disorders. Moreover, most published studies
have not considered all of the important confounding
variables.9 The impact of diabetes on the lives of people
with schizophrenia makes this area an important topic
for future research.
1. Mitchell AJ, Vancampfort D, De Herdt A, Yu W, De Hert
M. Is the prevalence of metabolic syndrome and metabolic
abnormalities increased in early schizophrenia? Acomparative meta-analysis of first episode, untreated and treated
patients [published online ahead of print August 27, 2012].
Schizophr Bull. doi:10.1093/schbul/sbs082
2. Lorenz WF. Sugar tolerance in dementia praecox and other
mental disorders. Arch Neurol Psychiatry. 1922;8:184196.
3. Cohn TA, Remington G, Zipursky RB, Azad A, Connolly
P, Wolever TM. Insulin resistance and adiponectin levels in
drug-free patients with schizophrenia: a preliminary report.
Can J Psychiatry. 2006;51:382386.
4. Spelman LM, Walsh PI, Sharifi N, Collins P, Thakore JH.
Impaired glucose tolerance in first-episode drug-nave
patients with schizophrenia. Diabet Med. 2007;24:481485.
5. Saddichha S, Manjunatha N, Ameen S, Akhtar S. Diabetes
and schizophreniaeffect of disease or drug? Results from a
randomized, double-blind, controlled prospective study in first-
episode schizophrenia. Acta Psychiatr Scand. 2008;117:342347.

The Author 2012. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
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*To whom correspondence should be addressed; Psychiatry, University of Cambridge, Herchel Smith Building, Forvie Site, Cambridge
CB2 0SZ, GB, UK; tel: +44 (0)1223 336961, e-mail:

E. Fernandez-Egea etal.

6. Sengupta S, Parrilla-Escobar MA, Klink R, etal. Are metabolic indices different between drug-nave first-episode
psychosis patients and healthy controls? Schizophr Res.
7. Fernandez-Egea E, Bernardo M, Donner T, etal. Metabolic
profile of antipsychotic-naive individuals with non-affective
psychosis. Br J Psychiatry. 2009;194:434438.

8. Kirkpatrick B, Messias E, Harvey PD, Fernandez-Egea E,

Bowie CR. Is schizophrenia a syndrome of accelerated aging?
Schizophr Bull. 2008;34:10241032.
9. Kirkpatrick B, Miller BJ, Garcia-Rizo C, Fernandez-Egea E,
Bernardo M. Is abnormal glucose tolerance in antipsychoticnaive patients with nonaffective psychosis confounded by
poor health habits? Schizophr Bull. 2012;38:280284.

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