The Influence of Depression, Positive Health Behaviors, and Weight Status on Glycated Hemoglobin: A Sequential Mediation Analysis of the INDEPENDENT Trial

J Gen Intern Med. 2025 Aug 13. doi: 10.1007/s11606-025-09810-1. Online ahead of print.

ABSTRACT

BACKGROUND: Collaborative care models (CoCM) improve both depression and cardiometabolic outcomes, but the mechanisms driving these effects remain unclear.

OBJECTIVE: To determine whether changes in depressive symptoms, positive health behaviors (PHBs), body mass index (BMI), and waist circumference mediate the effect of an adapted CoCM on glycemic control among adults with cardiometabolic risk in India.

DESIGN: Longitudinal structural equation modeling of data from the INtegrating DEPrEssioN and Diabetes TreatmENT (INDEPENDENT) Randomized Control Trial.

PARTICIPANTS: Adults in India with type 2 diabetes or elevated cardiometabolic risk factors and clinically significant depressive symptoms.

INTERVENTIONS: An adapted CoCM integrating behavioral activation (BA) within diabetes care, delivered by a multidisciplinary team to enhance engagement in self-care activities.

MAIN MEASURES: Intervention exposure was the independent variable; mediators were depressive symptoms (Symptom Checklist-20), PHBs (Summary of Diabetes Self-Care Activities), BMI, and waist circumference; the primary outcome was hemoglobin A1c (HbA1c). Confirmatory factor analyses ensured measurement validity, with second-order factors capturing depressive symptom domains (anhedonia, somatization, internalizing symptoms, restlessness).

KEY RESULTS: The intervention significantly reduced depressive symptoms from 0-6 months (β = -0.22, p < 0.01) and 6-12 months (β = -0.34, p < 0.01) and increased PHBs from 0-6 months (β = 0.15, p < 0.05) and 6-12 months (β = 0.11, p < 0.05). Higher depressive symptoms predicted lower PHBs at 6 months (β = -0.26, p < 0.01) and 12 months (β = -0.25, p < 0.01). PHBs mediated reductions in BMI (β = -0.08 to -0.09, p < 0.01) and waist circumference, which in turn mediated improvements in HbA1c.

CONCLUSIONS: An adapted CoCM improved glycemic control and cardiometabolic risk by alleviating depressive symptoms, enhancing PHBs, and reducing BMI and waist circumference. Integrating BA within CoCM may be a key mechanism for optimizing outcomes in integrated cardiometabolic care.

PMID:40804563 | DOI:10.1007/s11606-025-09810-1