Glucose Metabolism and Obesity in Bipolar Disorder

sirtravelalot_AdobeStock

RESEARCH UPDATE

CASE VIGNETTE

“Mr Samuel” is a 48-year-old Caucasian male with a 25-year history of bipolar I disorder with psychotic features and post-traumatic stress disorder (PTSD) who is seen for monthly outpatient visits. He has been clinically stable with no psychiatric hospitalizations in the past 15 years on a regimen of quetiapine 500 mg daily and valproic acid 750 mg daily. He has comorbid hypertension, for which he previously took valsartan and is currently taking lisinopril. He also has dyslipidemia, likely a familial hypertriglyceridemia, with a recent fasting total cholesterol of 244 mg/dL and triglycerides of 384 mg/dL, for which he was started on simvastatin. His fasting glucose is normal at 86 mg/dL. His body mass index has been stable at 26 for the past year.

Bipolar disorder is associated with increased cardiovascular disease morbidity and mortality.¹ However, there is not a corresponding increase in cardiovascular disease in the first-degree relatives of patients with bipolar disorder, suggesting a key role for factors inherent to the disorder and its treatment.² Obesity (both general and abdominal) and impaired glucose metabolism (including impaired fasting glucose and frank diabetes) are major risk factors for cardiovascular disease.

The Current Study

Liu and colleagues³ conducted a systematic review and meta-analysis of the pooled prevalence of type 2 diabetes mellitus, impaired fasting glucose, and general and abdominal obesity in patients with bipolar disorder. The authors systematically searched Embase, Medline, PubMed, and APA PsycArticles from inception through June 2021. They included 1) cross-sectional, retrospective, and prospective studies in English or Chinese; 2) studies that diagnosed bipolar disorder by DSM or ICD criteria; and 3) studies that used valid criteria to measure fasting glucose. Studies that were not peer-reviewed, did not quantitatively measure glucose or obesity, or only included children and adolescents were excluded. Data were analyzed using random-effects meta-analysis. The authors also used meta-regression analyses to assess the effects of the following covariates: age, sex, BMI, study design, and illness duration. Article quality was assessed using the Newcastle-Ottawa Scale.

The authors identified 6352 studies, of which 49 were included in the meta-analysis, including 32 cross-sectional, 15 retrospective, and 1 prospective study. Twenty-three studies recruited age- and sex-matched controls, and 23 studies met the criterion for satisfactory methodological quality. The pooled prevalence of type 2 diabetes in 23 studies (n=342,826) was 9.6% (95% CI 7.3-12.2%) and was moderated by older age and female sex. The pooled prevalence of impaired fasting glucose (ADA criteria of ≥100 mg/dL) in 21 studies (n=2454) was 22.4% (95% CI 16.7-28.7%), with no significant moderators. The pooled prevalence of impaired fasting glucose (WHO criteria of ≥110 mg/dL) in 11 studies (n=1582) was 14.8% (95% CI 10.8-19.3%) and was moderated by study design (higher prevalence in retrospective studies).

The pooled prevalence of obesity in 32 studies (n=322,494) was 29% (95% CI 22.8-35.6%), with no significant moderators. The pooled prevalence of abdominal obesity in 16 studies (n=2378) was 51.1% (95% CI 45.0-57.3%, and was moderated by longer illness duration and female sex. In 7 studies with controls, there was a 1.6-fold increased risk of diabetes in patients with bipolar disorder. In 11 studies with controls, there was a significant 1.7-fold increased risk of obesity in patients with bipolar disorder.

Study Conclusions

The authors found a 10% prevalence of type 2 diabetes, an approximate 20% prevalence of impaired glucose tolerance, an almost 30% prevalence of obesity, and an over 50% prevalence of abdominal obesity in patients with bipolar disorder. Study strengths included the large sample size; consideration of impaired glucose tolerance and abdominal obesity separate from diabetes and general obesity; and the consideration of several potential moderators. A primary limitation was the lack of data on pharmacotherapies.

The Bottom Line

Bipolar disorder is associated with an increased prevalence of diabetes, impaired fasting glucose, and general and abdominal obesity. Primary prevention, screening, and treatment efforts are needed for this patient population to mitigate increased cardiovascular disease morbidity and mortality.

Dr. Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times^TM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

References

1. Correll CU, Solmi M, Veronese N, et al. Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls [published correction appears in World Psychiatry. 2018 Feb;17 (1):120]. World Psychiatry. 2017;16(2):163-180.

2. Kessing LV, Ziersen SC, Andersen PK, Vinberg M. A nation-wide population-based longitudinal study mapping physical diseases in patients with bipolar disorder and their siblings. J Affect Disord. 2021;282:18-25.

3. Liu YK, Ling S, Lui LMW, et al. Prevalence of type 2 diabetes mellitus, impaired fasting glucose, general obesity, and abdominal obesity in patients with bipolar disorder: a systematic review and meta-analysis. J Affect Disord. 2022;300:449-461.