Additive interaction of hyperglycaemia and albuminuria on risk of ischemic stroke in type 2 diabetes mellitus – Hong Kong Diabetes Registry

Abstract

Objective The study aims to test whether biological interaction between hyperglycaemia and albuminuria can explain the inconsistent findings from epidemiological studies and clinical trials about effects of hyperglycemia on stroke in type 2 diabetes (T2DM).

Research design and methods 6445 Hong Kong Chinese patients with T2DM and free of stroke at enrolment were followed up for a median of 5.37 years. Spline Cox proportional hazard regression was used to obtain hazard ratio curves, which were used to identify cutoff points of glycated haemoglobin (HbA_1c) and spot urinary albumin to creatinine ratio (ACR) for increased stroke risk. The identified cut-off point of HbA1c was used to check biological interaction between HbA_1c and albuminuria (micro- and macro-albuminuria). The biological interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index.

Results During the follow-up period, 4.45% (n=287) patients developed ischemic stroke. HbA_1c was associated with increased hazard ratios of ischemic stroke in a near-linear manner except for two points, 6.2 % and 8.0 %, where the slope between these 2 points accelerated. For HbA1c values less than 6.2 %, the presence of micro/macro albuminuria did not confer additional risk while significant biological interaction between HbA1c and micro/macro albuminuria for values ≥6.2 % was observed (PERI=0.92, 95% CI: 0.16-1.68 and AP=0.40 95% CI: 0.01-0.78).

Conclusions: HbA1c ≥6.2 % and micro/macro albuminuria interact to markedly increase the ischemic stroke risk which explain a large proportion of risk in patients with T2DM harbouring both risk factors.