The Diverse Patterns of HbA1c from Childhood to Adolescence

Identifying high-risk patients with unstable HbA1c patterns from childhood to adolescence can have significant outcomes. 

The study conducted by Sherr et al. aimed to identify distinct trajectories of the young with type 1 diabetes (T1D) from diagnosis to 10 years after using three registries, German-Austrian-Luxembourgian-Swiss diabetes prospective follow-up initiative, also known as (Diabetes Patienten Verlaufsdokumentation (DPV); Australasian Diabetes Data Network (ADDN); and the US T1D Exchange Clinic Registry (T1DX). The Diabetes Control and Complications Trial (DCCT) has demonstrated that intensive insulin therapy can reduce rates of microvascular complications, thereby proving the importance of setting glycemic goals. The longitudinal follow-up in the EDIC trial demonstrated a reduction of macro and microvascular complications through intensive treatment over standard treatment, justifying yet again the urgency to obtain optimum glucose goals. However, among the youth with T1D, this has been difficult to achieve, thus leading to inadequate glucose control. A previous study using the Austrian and German diabetes registry by Schwandt et al. analyzed the transition from childhood to adolescence and discovered five distinct HbA1c trajectories, highlighting the course of HbA1c patterns irrespective of disease duration. Following the HbA1c patterns in the young from T1D onset as they mature will enable us to identify those at greater risk of suboptimal HbA1c and long-term complications due to their disease. 

The study included patients who were less than 18 years old at the time of being diagnosed with T1D, who had at least one measurement of HbA1c within one year of being diagnosed, and three or more duration years composite of HbA1c values over ten years of follow up. Seven thousand two hundred ninety-two participants were from the ADDN. Most of the participants were from the DPV at 39,226. The US T1D Exchange Clinic Registry included 3704 participants, a total of 50,222 patients. Participants with pancreas or islet cell transplants could not join the study. The ADDN transmitted de-identified data twice yearly from 20 adult and pediatric centers to the central database. Data submitted by the DPV included 500 centers from Germany, Luxembourg, Switzerland, and Austria, also de-identified and sent to Ulm University in Germany. The T1DX included more than 80 pediatric and adult endocrinology clinics specializing in diabetes. In addition, collected retrospective records were sent to the managing registry, including HbA1c over the past ten years. The composite HbA1c was used every year for assessment. The study used the HbA1c at the target range recommended by the American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD), ≤7%. HbA1c was further classified as near target 7 to 7.5% and above targe >7.5%. Nagin’s group-based trajectory modeling was utilized to assess data longitudinally for statistical analysis. Continuous variates, x2 tests, or Kruskal-Wallis were used to describe or compare trajectory groups among registries. 

The study assessed more than >50,000 participants, and all three registries had similar sex distributions. The age ranges slightly differed among the three groups as follows: T1DX 5 years old (interquartile range (IQR 3 to 8), DPV 8.8 years old (IQR 5.3 to 11.8), and ADDN 8.1 years old (IQR 4.7 to 11.2). Among the three registries, the study was able to identify 5 HbA1c trajectories, which were low stable, intermediate stable, high stable, target increase, and high increase. Patients with low or intermediate stable HbA1c were>50%, nearly 15% in each registry were classified as high stable >8% HbA1c, and approximately 11% started at near or at goal HbA1c but increased. Roughly 5% of the participants were classified as high increase, were above goal from their diagnosis, and HbA1c progressed through the years. This group was distinct from the rest by having older ages at the time of T1D diagnosis and the most considerable rates of minority status among the three registries (p≤0.001). A limitation of the current study includes demographic elements such as socioeconomic status, BMI, or level of education not being evaluated and how they might influence the trajectories of HbA1c in young patients. It appears beneficial for additional studies to explore this area. 

Practical Pearls: 

• 5 HbA1c trajectories of HbA1c from the time of T1D diagnosis to a 10-year follow-up were identified: low stable, intermediate stable, high stable, target increase, and high increase. 
• The longitudinal follow-up of childhood to adolescent HbA1c allows for identifying those who are more at risk of HbA1c worsening; thus, early or aggressive treatment can be initiated to prevent complications of the disease. 
• Being classified as a minority and diagnosed at an older age were among the 5% of the study population classified as high increase, a potential group for an increase of HbA1c declination. 

References for “The Diverse Patterns of HbA1c from Childhood to Adolescence”:
Sherr, Jennifer L et al. “Hemoglobin A1c Patterns of Youth With Type 1 Diabetes 10 Years Post Diagnosis From 3 Continents.” Pediatrics vol. 148,2 (2021): e2020048942. doi:10.1542/peds.2020-048942.  

Schwandt A, Hermann JM, Rosenbauer J, et al; DPV Initiative. Longitudinal trajectories of metabolic control from childhood to young adulthood in type 1 diabetes from a large German/Austrian registry: a group-based modeling approach. Diabetes Care. 2017;  

Trina Maglalang RPh, PharmD Candidate University of Colorado Skaggs School of Pharmacy