A Plasma Metabolite Score Related to Psychological Distress and Diabetes Risk: A Nested Case-control Study in US Women

Tianyi Huang; Yiwen Zhu; Katherine H Shutta; Raji Balasubramanian; Oana A Zeleznik; Kathryn M Rexrode; Clary B Clish; Qi Sun; Frank B Hu; Laura D Kubzansky; Susan E Hankinson

doi:10.1210/clinem/dgad731

A Plasma Metabolite Score Related to Psychological Distress and Diabetes Risk: A Nested Case-control Study in US Women

J Clin Endocrinol Metab. 2023 Dec 13:dgad731. doi: 10.1210/clinem/dgad731. Online ahead of print.

Authors

Tianyi Huang^{1

2}, Yiwen Zhu³, Katherine H Shutta^{1

4}, Raji Balasubramanian⁵, Oana A Zeleznik¹, Kathryn M Rexrode^{6

7}, Clary B Clish⁸, Qi Sun^{1

3

9}, Frank B Hu^{1

3

9}, Laura D Kubzansky¹⁰, Susan E Hankinson⁵

Affiliations

¹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
² Division of Sleep Medicine, Harvard Medical School, Boston, MA.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
⁴ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
⁵ Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA.
⁶ Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
⁷ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
⁸ Broad Institute of MIT and Harvard, Boston, MA.
⁹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
¹⁰ Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA.

PMID: 38092374
DOI: 10.1210/clinem/dgad731

Abstract

Context: Psychological distress has been linked to diabetes risk. Few population-based, epidemiologic studies have investigated the potential molecular mechanisms (e.g., metabolic dysregulation) underlying this association.

Objective: To evaluate the association between a metabolomic signature for psychological distress and diabetes risk.

Methods: We conducted a nested case-control study of plasma metabolomics and diabetes risk in the Nurses' Health Study, including 728 women (mean age: 55.2 years) with incident diabetes and 728 matched controls. Blood samples were collected between 1989-1990 and incident diabetes was diagnosed between 1992-2008. Based on our prior work, we calculated a weighted plasma metabolite-based distress score (MDS) comprised of 19 metabolites. We used conditional logistic regression accounting for matching factors and other diabetes risk factors to estimate odds ratios (OR) and 95% CI for diabetes risk according to MDS.

Results: After adjusting for sociodemographic factors, family history of diabetes, and health behaviors, the OR (95% CI) for diabetes risk across quintiles of the MDS was 1.00 (reference) for Q1, 1.16 (0.77, 1.73) for Q2, 1.30 (0.88, 1.91) for Q3, 1.99 (1.36, 2.92) for Q4, and 2.47 (1.66, 3.67) for Q5. Each SD increase in MDS was associated with 36% higher diabetes risk (95% CI: 1.21, 1.54; p-trend<0.0001). This association was moderately attenuated after additional adjustment for BMI (comparable OR: 1.17; 95% CI: 1.02, 1.35; p-trend=0.02). The MDS explained 17.6% of the association between self-reported psychological distress (defined as presence of depression or anxiety symptoms) and diabetes risk (p=0.04).

Conclusions: MDS was significantly associated with diabetes risk in women. These results suggest that differences in multiple lipid and amino acid metabolites may underlie the observed association between psychological distress and diabetes risk.

Keywords: Anxiety; Depression; Diabetes Mellitus; Female; Metabolomics; Middle Aged; Type 2.