Depression and Long-Term HbA1c Variability Are Additively Associated With Increased Risk of Cardiovascular-Renal Outcomes, Severe Hypoglycaemia and Mortality in Type-2 Diabetes
In brief
Depression raises cardiovascular risk by roughly 80% in type-2 diabetes
In a Hong Kong cohort of 5,657 adults with type-2 diabetes, patients scoring at least 7 on the PHQ-9 had a 79% higher chance of cardiovascular events after adjusting for other factors. High long-term HbA1c variability independently increased kidney disease and severe hypoglycemia risk, and the combination of depression plus variable glucose led to the worst outcomes, highlighting the need for routine mood screening and stable glycemic control.
- Journal
- Diabetes/metabolism research and reviews (Q1)
- Published
- 1 September 2026
- Study design
- Unclassified
- Evidence level
- Level 5, Expert Opinion (CEBM 5)
- Authors
- Kelly T C Wong, Edith W K Chow, Eric S H Lau, Chun Kwan O, Alice P S Kong, Ronald C W Ma, et al.
- PMID
- 42671118
- DOI
- 10.1002/dmrr.70222
Why clinicians should know about it
- Picked for Internal Medicine (paper of the day, 5 September 2026): Depression + HbA1c variability worsens outcomes
Abstract
AIMS: Depression and long-term HbA1c variability are associated with adverse outcomes in type-2 diabetes (T2D), which may be related to suboptimal self-management practices and health-related quality of life (HRQoL). MATERIALS AND METHODS: In the prospective Hong Kong Diabetes Register (2013-2019), we estimated the independent and joint associations of depression and HbA1c variability with outcomes. Depression was measured using the Patient Health Questionnaire-9 (PHQ-9) with a validated Chinese cut-off score ≥ 7. The HbA1c variability score (HVS) was expressed as the percentage of HbA1c, which varied by 0.5% compared to the preceding value. RESULTS: Amongst 5657 Chinese patients with T2D [58.7% male, age (mean ± SD): 58.47 ± 10.62 years, duration of diabetes: 10.63 ± 8.19 years and time-weighted HbA1c: 7.44% ± 1.04%], 13.3% had depression. After full adjustment, depression was associated with increased risk of cardiovascular disease (CVD) [adjusted hazard ratio (aHR): 1.79 (95% CI: 1.15-2.79); p = 0.010], whereas high HVS (≥ median, 42.9%) was associated with increased risks of chronic kidney disease (CKD) [1.49 (1.21-1.82); p < 0.001] and severe hypoglycaemia (SH) [1.93 (1.22-3.07); p = 0.005]. The depression-high-HVS group had the highest aHR for CKD, which was attenuated from 1.90 (1.41-2.56) to 1.74 (1.25-2.44), and that for all-cause mortality from 2.00 (1.33-3.01) to 1.72 (1.06-2.78) after adjustment for self-management practices and HRQoL. CONCLUSIONS: Depression and high HVS are independently and differentially associated with adverse events, with the depression-high-HVS group having the worst outcomes, which were modulated by self-management and HRQoL, calling for systematic screening of depression and holistic management aimed at avoiding fluctuating glycaemic control in T2D.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.