HbA1c variability as an independent risk factor for diabetic retinopathy in type 1 diabetes: a German/Austrian multicenter analysis on 35,891 patients

Abstract

Objective: This study aimed to analyze the effect of HbA1c variability on the occurrence of diabetic retinopathy in type 1 diabetes patients.

Patients and methods: 35,891 patients with childhood, adolescent or adult onset of type 1 diabetes from a large multicentre survey, the German/Austrian prospective documentation system (DPV), were analysed. Cox proportional hazard models were used to examine whether intra-individual HbA1c variability expressed as variation coefficient is an independent risk factor for the occurrence of diabetic retinopathy.

Results: Kaplan-Meier curves stratified by median HbA1c and variation coefficient revealed that retinopathy-free survival probability is lower when both median HbA1c and HbA1c variability are above the 50th percentile. Cox regression models confirmed this finding: After adjustment for age at diabetes onset, gender and median HbA1c, HbA1c variability was independently associated with the occurrence of diabetic retinopathy. Time-covariate interactions used to model non-proportionality indicated an effect decreasing with duration of diabetes for both median HbA1c and HbA1c variability. Predictive accuracy increased significantly when adding HbA1c variability to the Cox regression model.

Conclusions: In patients with type 1 diabetes, HbA1c variability adds to the risk of diabetic retinopathy independently of average metabolic control.

Figure 1. Kaplan Meier curves for retinopathy-free survival according to intrapersonal HbA_1c-MEDIAN and HbA_1c-CV above/below 50^th group percentile.

Green line: HbA_1c-MEDIAN below, HbA_1c-CV below 50^th group percentile. Blue line: HbA_1c-MEDIAN below, HbA_1c-CV above 50^th group percentile. Red line: HbA_1c-MEDIAN above, HbA_1c-CV below 50^th group percentile. Orange line: HbA_1c-MEDIAN above, HbA_1c-CV above 50^th group percentile. Patients were assigned to strata based on group-specific 50^th percentiles according to duration of diabetes, age and gender. Log-rank test was used for comparisons among strata.