Depression and Long‐Term HbA 1c Variability Are Additively Associated With Increased Risk of Cardiovascular–Renal Outcomes, Severe Hypoglycaemia and Mortality in Type‐2 Diabetes

Aims 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). Materials and Methods 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. 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 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. 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.