Parsing metabolic heterogeneity in mood disorders: A hypothesis-driven cluster analysis of glucose and insulin abnormalities.

Abstract

OBJECTIVES:

Metabolically based distinctions for disturbances in glucose and insulin may provide meaningful insights both clinically and mechanistically.

METHODS:

Data were derived from 352 subjects of previously completed clinical studies with a mood disorder (MD) (bipolar disorder: n = 179, major depressive disorder: n = 173) and 218 healthy controls from the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy. We conducted a factor analysis to replicate a priori dissociable factors informed by glucose and insulin levels and indices of insulin resistance and beta-cell function: elevated insulin and insulin resistance ("insulin-IR"), and increased fasting glucose and reduced insulin secretion ("glucotoxicity"). Cluster analyses were conducted, separately in men and women, to evaluate the clinical relevance of subtyping individuals with MDs using insulin-IR and glucotoxicity (GT) factor scores.

RESULTS:

Factors insulin-IR and GT explained 92.64% and 92.09% of the variance in men and women respectively. Three clusters were replicated in men and women separately: metabolically healthy (MH), high GT, and insulin-resistant (IR). After adjusting for age, gender, study cohort, MD diagnosis, and antipsychotics use, body mass index (BMI) and mean arterial pressure were higher in IR- vs GT- or MH-clustered individuals; GT-clustered individuals had more metabolic syndrome components and higher C-reactive protein. Glucotoxic-clustered subjects reported greater impairments in cognitive function and global functioning when compared to MH- or IR-clustered subjects.

CONCLUSIONS:

Using simple, cost-effective, and accessible measures, we identified stable, gender-convergent, subgroups of individuals that significantly diverged on measures of cognitive dysfunction, self-reported anhedonia, functional disability, BMI, and blood pressure.

• Authors: Rodrigo B Mansur, Yena Lee, Mehala Subramaniapillai, Danielle S Cha, Elisa Brietzke, Roger S McIntyre
• Journal: Bipolar disorders (Bipolar Disord) Vol. 22 Issue 1 Pg. 79-88 (02 2020) ISSN: 1399-5618 [Electronic] Denmark
• PMID: 31464359 (Publication Type: Journal Article)
• Copyright: © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Blood Glucose
• Insulin
• C-Reactive Protein

Topics

• Adult
• Anhedonia
• Bipolar Disorder (blood, diagnosis)
• Blood Glucose (metabolism)
• C-Reactive Protein (analysis)
• Cluster Analysis
• Cognitive Dysfunction (diagnosis)
• Depressive Disorder, Major (blood, diagnosis)
• Female
• Humans
• Insulin (blood)
• Insulin Resistance
• Male
• Metabolic Syndrome (diagnosis, psychology)
• Middle Aged
• Risk Factors