Clinically meaningful and lasting HbA1c improvement rarely occurs after 5 years of type 1 diabetes: an argument for early, targeted and aggressive intervention following diagnosis

Abstract

Aims/hypothesis: Our objectives were to explore whether the phenomenon of HbA_1c 'tracking' occurs in individuals with type 1 diabetes, how long after diagnosis does tracking take to stabilise, and whether there is an effect of sex and age at diagnosis on tracking.

Methods: A total of 4525 individuals diagnosed with type 1 diabetes between 1 January 1995 and 1 May 2015 were identified from The Health Improvement Network (THIN) database. Mixed models were applied to assess the variability of HbA_1c levels over time with random effects on general practices (primary care units) and individuals within practices.

Results: 4525 individuals diagnosed with type 1 diabetes were identified in THIN over the study period. The greatest difference in mean HbA_1c measurement (-7.0 [95% CI -8.0, -6.1] mmol/mol [0.6%]) was seen when comparing measurements made immediately after diagnosis (0-1 year since diagnosis) with those at 10 or more years (the reference category). The mean difference in HbA_1c for the successive periods compared with 10 or more years after diagnosis declined and was no longer statistically significant after 5 years. In the stratified analysis using sex and age group there was considerable heterogeneity with adult onset type 1 diabetes appearing to track earlier and at a lower mean HbA_1c.

Conclusions/interpretation: In individuals with type 1 diabetes, glycaemic control measured by HbA_1c settles onto a long-term 'track' and this occurs on average by 5 years following diagnosis. Age at diagnosis modifies both the rate at which individuals settle into their track and the absolute HbA_1c tracking level for the next 10 years.

Keywords: Glycated haemoglobin; HbA1c; Tracking; Type 1 diabetes mellitus.

Fig. 1

Mean HbA_1c by year from diagnosis of type 1 diabetes in 4525 patients with newly diagnosed diabetes. For example, duration time 0 represents the HbA_1c values captured from date of diagnosis to year 1; time 1 represents the HbA_1c measurements from year 1 to 2, and time 9 represents HbA1c measurements from year 9 to 10

Fig. 2

Mean (95% CI) difference in HbA_1c between the mean for the reference group (≥10 years post diagnosis) and the mean for each year after diagnosis. Duration time 0 represents the HbA_1c values captured from date of diagnosis to year 1; time 1 represents the HbA_1c measurements from year 1 to 2, etc. Models were constructed using a random intercept and slopes model adjusting for age, sex and Townsend index. The time point at which the 95% CI for the yearly difference crosses the null value (zero) is considered the starting point of tracking

Fig. 3

Difference in HbA_1c between the reference group (≥10 years) and each year after the time of diagnosis of type 1 diabetes stratified by age at diagnosis and sex. Duration time 0 represents the HbA_1c values captured from date of diagnosis to year 1; time 1 represents the HbA_1c measurements from year 1 to 2, etc. (a, e) Diagnosis between ages 0 and 10 years; (b, f) between ages 10 and 20 years; (c, g) between ages 20 and 30 years; (d, h) between ages 30 and 40 years; male group (a–d) and female group (e–h). Models were constructed using a random intercept and slopes model adjusting for age, sex and Townsend index. The difference is given for each year with a point estimate and its 95% CI. The time point where the above difference crosses the null value (zero) is considered the starting point of tracking