Early increase in HbA1c trajectory predicts development of severe microangiopathy in patients with type 1 diabetes: the VISS study

Abstract

Introduction: To study the HbA1c trajectory from the time of diagnosis to examine if patients at the greatest risk for severe microangiopathy can be identified early allowing clinicians to intervene as soon as possible to avoid complications.

Research design and methods: In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age, 1983-1987, were followed from diagnosis until 2019. Mean HbA1c was calculated each year for each patient. Severe diabetic microangiopathy was defined as proliferative diabetic retinopathy (PDR) or macroalbuminuria (nephropathy).

Results: After 32 years, 27% had developed PDR and 8% macroalbuminuria. Patients with weighted HbA1c (wHbA1c); <57 mmol/mol; <7.4% did not develop PDR or macroalbuminuria. The HbA1c trajectories for patients developing PDR and macroalbuminuria follow separate courses early on and stay separated for 32 years during the follow-up. Patients without severe complications show an initial dip, after which HbA1c slowly increases. HbA1c in patients with severe complications directly rises to a high level within a few years. Mean HbA1c calculated for the period 5-8 years after diabetes onset strongly predicts the development of severe complications. Females with childhood-onset diabetes exhibit a high peak in HbA1c during adolescence associated with higher wHbA1c and higher prevalence of PDR.

Conclusions: The HbA1c trajectory from diabetes onset shows that mean HbA1c for the period 5-8 years after diagnosis strongly predicts severe microangiopathy. Females with childhood-onset diabetes exhibit a high peak in HbA1c during adolescence associated with higher wHbA1c and a higher prevalence of PDR.

Keywords: Diabetes Mellitus, Type 1; Diabetic Angiopathies; Glycated Hemoglobin A.

Figure 1. Yearly mean HbA1c values (A) in relation to age and (B) in relation to age and sex. Error bars denotes 95% CIs.

Figure 2. Yearly mean HbA1c values in patients with type 1 diabetes, (A) in relation to diabetes duration in males and females diagnosed before 18 years of age and (B) in relation to diabetes duration in males and females diagnosed at an age of 18 years or later. Error bars denotes 95% CIs.

Figure 3. (A) Yearly mean HbA1c values in relation to duration in patients with and without proliferative diabetic retinopathy, (B) yearly mean HbA1c values in relation to duration in patients with and without macroalbuminuria. Error bars denotes 95% CIs.

Figure 4. Quartiles of mean HbA1c for the period 5–8 years after diabetes onset related to PDR and nephropathy. Compared with HbA1c <7.4%, the increase was significant (p<0.001) at HbA1c 8.3–9.4% and >9.4% for PDR and >9.4% for macroalbuminuria (p<0.001). Expressed in mmol/mol <7.4%=<57; 7.4–8.2%=57–66; 8.3–9.4%=67–79; >9.4%=>79. PDR, proliferative diabetic retinopathy.