HbA1c Variability as an Independent Risk Factor for Diabetic Retinopathy in Type 1 Diabetes: A German/Austrian Multicenter Analysis on 35,891 Patients

Abstract

ObjectiveThis study aimed to analyze the effect of HbA1c variability on the occurrence of diabetic retinopathy in type 1 diabetes patients.Patients and Methods35,891 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.ResultsKaplan-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.ConclusionsIn patients with type 1 diabetes, HbA1c variability adds to the risk of diabetic retinopathy independently of average metabolic control.

Risk factors for development and progression of diabetic retinopathy in Dutch patients with type 1 diabetes mellitus

“…(2013b) and Hermann et al. (2014) also reported HbA1c variability as a risk factor for development of DR independently of average glycaemic control. Kilpatrick (2012) proposed several explanatory mechanisms for this correlation.…”

Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis

“…Twenty studies in 87,641 participants met the inclusion criteria. Ten studies included participants from Europe (10,11,14,(16)(17)(18)(19)26,29,35,36), eight from Asia (12,13,15,18,20,24,27,28), four from North America (6,18,23, 25), and one from Australasia (18). The number of participants in each study ranged from 234 to 35,891.…”

“…Seven studies included 44,021 participants with type 1 diabetes (6,10,11,14,25,29,35). These comprised three retrospective cohort studies (11,14,25), two prospective cohort studies (10,29), one post hoc analysis of a randomized controlled trial (6), and one cross-sectional study (35).…”

“…A recent meta-analysis concluded that HbA 1c variability, assessed by the SD, is associated with renal disease in type 1 and type 2 diabetes (9). However, no systematic reviews or meta-analyses have evaluated the relationship between long-term glycemic variability and other complications in diabetes, despite contradictory literature providing evidence in support (6,(10)(11)(12)(13)(14)(15) and against (16)(17)(18)(19)(20) such a relationship.…”

“…First, unlike short-term glycemic variability, longterm glycemic variability may predict complications in both type 1 and type 2 diabetes (6,(10)(11)(12)(13)(14)(15)(21)(22)(23)(24)(25)(26)(27)(28)(29). Second, HbA 1c is routinely recorded in primary care for both types of diabetes, whereas measures of short-term variability are not (30,31).…”