Depression and Long-Term HbA_1c Variability Are Additively Associated With Increased Risk of Cardiovascular-Renal...

Depression and long-term HbA_1c 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).

In the prospective Hong Kong Diabetes Register (2013-2019), we estimated the independent and joint associations of depression and HbA_1c variability with outcomes. Depression was measured using the Patient Health Questionnaire-9 (PHQ-9) with a validated Chinese cut-off score ≥ 7. The HbA_1c variability score (HVS) was expressed as the percentage of HbA_1c, which varied by 0.5% compared to the preceding value.

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 HbA_1c: 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.

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.