This issue of Acta Psychiatrica Scandinavica contains an interesting discussion paper by Garcia-Rizo et al. entitled ‘Is bipolar disorder an endocrine condition?: glucose abnormalities in bipolar disorder’. The paper discusses the possible interaction of metabolic disturbances in newly diagnosed, drug-naïve subjects with bipolar disorder. The authors disclose preliminary results showing a high prevalence of abnormal glucose tolerance in subjects with newly diagnosed bipolar disease (before disease-specific treatment for the psychiatric disorder has begun).

It has been known for several years that subjects with psychiatric disease, for example schizophrenia have several-fold increased mortality rates and this has been linked to increased cardiovascular risk [1]. Traditionally, the use of antipsychotic treatment has been assumed to be the main driving force for the increased mortality. It is evident that several components of the metabolic syndrome and bipolar disease are overlapping [2]. Thus, similarities such as disturbed glucose tolerance, imbalances in the hypothalamic–pituitary–adrenal axis, and sympathetic nervous system are overlapping between the two.

It is of outmost importance to study drug-naïve subjects for two reasons, namely 1. to increase our understanding of early dysmetabolic markers, for example impaired glucose tolerance and 2. tools that may help us identifying those at particular risk of cardiovascular disease.

The authors have previously shown that subjects with schizophrenia vs. matched controls have a disturbed glucose tolerance in spite of normal glycated hemoglobin (HbA1c) [3]. HbA1c is the method of choice for diagnosing diabetes and recommended by the WHO [4]. Abnormalities in glucose tolerance increase the risk for type 2 diabetes and cardiovascular disease. Thus, it is known that isolated abnormal glucose tolerance without elevated HbA1c conveys a cardiovascular mortality risk comparable to that seen in overt type 2 diabetes [5]. If the abnormal glucose tolerance in bipolar patients is as prevalent as stated in the paper (six of seven subjects) by Garcia-Rizo et al., this may be the first step to consider implementing the oral glucose tolerance test (OGTT) in the diagnostic armamentarium for subjects newly diagnosed with bipolar disease. Therefore, and not surprisingly, in a subject with a HbA1c below 48 mmol/mol (6.5%), an abnormal glucose tolerance may be the sole indicator of increased risk. Garcia-Rizos' paper points to the need for a more sophisticated diagnostic approach to the patient with mental disorder. We may benefit from screening for glucose metabolic disorders not detected just by rigid measurement of HbA1c. Further studies are warranted.

However, the preliminary data revealed by Garcia-Rizo et al. should be carefully interpreted for reasons mentioned already in the discussion paper, that is, the low number of bipolar subjects that underwent the main outcome test, namely the oral glucose tolerance test. Unhealthy living including smoking, drug and alcohol abuse, skewed eating habits, etc. all puts even more metabolic stress onto the fire—these confounding data need to be presented. In addition, we have no clear indication from the paper to determine the phase of the bipolar disease in which the subjects were studied. The glucose tolerance test may well be differentially affected by the subjects disease phase. Furthermore, one should keep in mind the extreme stress these newly diagnosed subjects undergo in the rollercoaster of mental ups-and-downs in the period preceding the OGTT. Mental, physical, and drug-induced stress potentially alters the glucose tolerance.

It is important not to underrate the findings by Garcia-Rizo et al. Seen from the clinicians—both the psychiatrists and endocrinologists — view-point the clinical impact of the results may, however, sadly be very limited. This is due to the fact that compliance even in non-psychiatric subjects is far from optimal and medication with multiple drugs may seem impossible. This should not limit our on-going research and certainly should not impede our good intentions and efforts for this group of diseased subjects. In this respect, non-pharmacologic life-style interventions should be a cornerstone given the evidence that, for example, exercise clearly has positive effects on psychiatric disorders such as depression.

No matter—if bipolar disorder is an endocrine condition or not—the psychiatrists have understood the lesson already and extensive implementation of prompt and continuous screening programmes in this high-risk population for cardiovascular risk factors will undoubtedly lower the increased cardiovascular morbidity and mortality of subjects with bipolar disorder.


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  2. References
  • 1
    Westman J, Hällgren J, Wahlbeck K et al. Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden. BMJ Open 2013;3:e002373.
  • 2
    Taylor V, MacQueen G. Associations between bipolar disorder and metabolic syndrome: a review. J Clin Psychiatry 2006;67:10341041.
  • 3
    Fernandez-Egea E, Bernardo M, Donner T et al. Metabolic profile of antipsychotic-naive individuals with non-affective psychosis. Br J Psychiatry 2009;194:434438.
  • 4
    WHO. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus. WHO/NMH/CHP/CPM/11.1. Available in
  • 5
    Silbernagel G, Sourij H, Grammer TB et al. Isolated post-challenge hyperglycaemia predicts increased cardiovascular mortality. Atherosclerosis 2012;225:194199.