Skip to main content
×
×
Home

Insulin resistance and outcome in bipolar disorder

  • Cynthia V. Calkin (a1), Martina Ruzickova (a1), Rudolf Uher (a2), Tomas Hajek (a3), Claire M. Slaney (a4), Julie S. Garnham (a4), M. Claire O'Donovan (a1) and Martin Alda (a3)...
Abstract
Background

Little is known about the impact of insulin resistance on bipolar disorder.

Aims

To examine the relationships between insulin resistance, type 2 diabetes and clinical course and treatment outcomes in bipolar disorder.

Method

We measured fasting glucose and insulin in 121 adults with bipolar disorder. We diagnosed type 2 diabetes and determined insulin resistance. The National Institute of Mental Health Life Chart was used to record the course of bipolar disorder and the Alda scale to establish response to prophylactic lithium treatment.

Results

Patients with bipolar disorder and type 2 diabetes or insulin resistance had three times higher odds of a chronic course of bipolar disorder compared with euglycaemic patients (50% and 48.7% respectively v. 27.3%, odds ratio (OR) = 3.07, P = 0.007), three times higher odds of rapid cycling (38.5% and 39.5% respectively v. 18.2%, OR = 3.13, P = 0.012) and were more likely to be refractory to lithium treatment (36.8% and 36.7% respectively v. 3.2%, OR = 8.40, P<0.0001). All associations remained significant after controlling for antipsychotic exposure and body mass index in sensitivity analyses.

Conclusions

Comorbid insulin resistance may be an important factor in resistance to treatment in bipolar disorder.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Insulin resistance and outcome in bipolar disorder
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Insulin resistance and outcome in bipolar disorder
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Insulin resistance and outcome in bipolar disorder
      Available formats
      ×
Copyright
Corresponding author
Martin Alda, Room 3088, Abbie J. Lane Building, 5909 Veterans' Memorial Lane, Halifax, Nova Scotia, B3H 2E2, Canada. Email: malda@dal.ca
Footnotes
Hide All

This study was funded by grants to C.V.C. from the Brain and Behaviour Research Foundation (formerly the National Alliance for Research on Schizophrenia and Depression, grant number 1003065-NARSAD-CALKIN) and the Capital Health Research Fund (grant number CDHA/RS-2002-061) and to M.A. from the Canadian Institute of Health Research (CIHR grant number 64410).

Declaration of interest

None.

Footnotes
References
Hide All
1 Cassidy, F, Ahearn, E, Carroll, BJ. Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients. Am J Psychiatry 1999; 156: 1417–20.
2 Lilliker, SL. Prevalence of diabetes in a manic-depressive population. Compr Psychiatry 1980; 21: 270–5.
3 McIntyre, RS, Konarski, JZ, Misener, VL, Kennedy, SH. Bipolar disorder and diabetes mellitus: epidemiology, etiology, and treatment implications. Ann Clin Psychiatry 2005; 17: 8393.
4 Osby, U, Brandt, L, Correia, N, Ekbom, A, Sparen, P. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry 2001; 5: 844–50.
5 Ruzickova, M, Slaney, C, Garnham, J, Alda, M. Clinical features of bipolar disorder with and without comorbid diabetes mellitus. Can J Psychiatry 2003; 48: 458–61.
6 Calkin, C, Van de Velde, C, Ruzickova, M, Slaney, C, Garnham, J, Hajek, T, et al. Can body mass index help predict outcome in patients with bipolar disorder? Bipolar Disord 2009; 11: 650–6.
7 Kemp, DE, Gao, K, Chan, PK, Ganocy, SJ, Findling, RL, Calabrese, JR. Medical comorbidity in bipolar disorder: relationship between illnesses of the endocrine/metabolic system and treatment outcome. Bipolar Disord 2010; 12: 404–13.
8 Endicott, J, Spitzer, RL. A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 1978; 35: 837–44.
9 Spitzer, RL, Endicott, J, Robins, E. Research diagnostic criteria: rationale and reliability. Arch Gen Psychiatry 1978; 35: 773–82.
10 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn, text revision) (DSM-IV-TR). APA, 2000.
11 Rucker, J, Newman, S, Gray, J, Gunasinghe, C, Broadbent, M, Brittain, P, et al. OPCRIT+: an electronic system for psychiatric diagnosis and data collection in clinical and research settings. Br J Psychiatry 2011; 199: 151–5.
12 Denicoff, KD, Leverich, GS, Nolen, WA, Rush, AJ, McElroy, SL, Keck, PE, et al. Validation of the prospective NIMH-Life-Chart Method (NIMH-LCM-p) for longitudinal assessment of bipolar illness. Psychol Med 2000; 30: 1391–7.
13 Denicoff, KD, Ali, SO, Sollinger, AB, Smith-Jackson, EE, Leverich, GS, Post, RM. Utility of the daily prospective National Institute of Mental Health Life-Chart Method (NIMH-LCM-p) ratings in clinical trials of bipolar disorder. Depress Anxiety 2002; 15: 19.
14 Grof, P, Duffy, A, Cavazzoni, P, Grof, E, Garnham, J, MacDougall, M, et al. Is response to prophylactic lithium a familial trait? J Clin Psychiatry 2002; 63: 942–7.
15 Garnham, J, Munro, A, Slaney, C, MacDougall, M, Passmore, M, Duffy, A, et al. Prophylactic treatment response in bipolar disorder: results of a naturalistic observation study. J Affect Disord 2007; 104: 185–90.
16 Manchia, M, Adli, M, Akula, N, Ardau, R, Aubry, JM, Backlund, L, et al. Assessment of response to lithium maintenance treatment in bipolar disorder: a Consortium on Lithium Genetics (ConLiGen) report. PLoS One 2013; 8: e65636.
17 Jones, SH, Thornicroft, G, Coffey, M, Dunn, G. A brief mental health outcome scale – reliability and validity of the Global Assessment of Functioning (GAF). Br J Psychiatry 1995; 166: 654–9.
18 Andreasen, NC, Endicott, J, Spitzer, RL, Winokur, G. The family history method using diagnostic criteria. Reliability and validity. Arch Gen Psychiatry 1977; 34: 1229–35.
19 Katsuki, A, Sumida, Y, Gabazza, EC, Murashima, S, Furuta, M, Araki-Sasaki, R, et al. Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes. Diabetes Care 2001; 24: 362–5.
20 Wallace, TM, Levy, JC, Matthews, DR. Use and abuse of HOMA modeling. Diabetes Care 2004; 27: 1487–95.
21 Esteghamati, A, Ashraf, H, Khalilzadeh, O, Zandieh, A, Nakhjavani, M, Rashidi, A, et al. Optimal cut-off of homeostasis model assessment of insulin resistance (HOMA-IR) for the diagnosis of metabolic syndrome: third national surveillance of risk factors of non-communicable diseases in Iran (SuRFNCD-2007). Nutr Metab 2010; 7: 2633.
22 Wongwananuruk, T, Rattanachaiyanont, M, Leerasiri, P, Indhavivadhana, S, Techatraisak, K, Angsuwathana, S, et al. The usefulness of homeostatic measurement assessment-insulin resistance (HOMA-IR) for detection of glucose intolerance in Thai women of reproductive age with polycystic ovary syndrome. Int J Endocrinol 2012; 57: 1035.
23 Matthews, DR, Hosker, JP, Rudenski, AS, Naylor, BA, Treacher, DF, Turner, RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–9.
24 Uher, R, Tansey, KE, Malki, K, Perlis, RH. Biomarkers predicting treatment outcome in depression: what is clinically significant? Pharmacogenomics 2012; 13: 233–40.
25 Yood, MU, DeLorenze, G, Quesenberry, CP Jr, Oliveria, SA, Tsai, AL, Willey, VJ, et al. The incidence of diabetes in atypical antipsychotic users differs according to agent: results from a multisite epidemiologic study. Pharmacoepidemiol Drug Saf 2009; 18: 791–9.
26 Wallum, BJ, Taborsky, GJ Jr, Porte, D Jr, Figlewicz, DP, Jacobson, L, Beard, JC, et al. Cerebrospinal fluid insulin levels increase during intravenous insulin infusions in man. J Clin Endocrinol Metab 1987; 64: 190–4.
27 Craft, S, Watson, GS. Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol 2004; 3: 169–78.
28 Hajek, T, Calkin, C, Blagdon, R, Slaney, C, Alda, M. Type 2 Diabetes mellitus: a potentially modifiable risk factor for neurochemical brain changes in bipolar disorders. Biol Psychiatry 2013; Nov 13 (Epub ahead of print).
29 Hajek, T, Calkin, C, Blagdon, R, Slaney, C, Uher, R, Alda, M. Insulin resistance, diabetes mellitus and brain structure in bipolar disorders. Neuropsychopharmacology 2014; June 19 (Epub ahead of print).
30 McIntyre, RS, Danilewitz, M, Liauw, SS, Kemp, DE, Nguyen, HT, Kahn, LS, et al. Bipolar disorder and metabolic syndrome: an international perspective. J Affect Disord 2010; 126: 366–87.
31 Kaidanovich-Beilin, O, Cha, DS, McIntyre, RS. Crosstalk between metabolic and neuropsychiatric disorders. F1000 Biol Rep 2012; 4: 1424.
32 Calkin, CV, Gardner, DM, Ransom, T, Alda, M. The relationship between bipolar disorder and type 2 diabetes: more than just co-morbid disorders. Ann Med 2012; 45: 171–81.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Insulin resistance and outcome in bipolar disorder

  • Cynthia V. Calkin (a1), Martina Ruzickova (a1), Rudolf Uher (a2), Tomas Hajek (a3), Claire M. Slaney (a4), Julie S. Garnham (a4), M. Claire O'Donovan (a1) and Martin Alda (a3)...
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *