Earlier Onset of T1D Linked With Poorer Glycemic Control

Young age at type 1 diabetes (T1D) onset plays a substantial role in subsequent glycemic control and the presence of albuminuria, according to study results published in BMJ Open Diabetes Research & Care. Findings also showed patients with early-onset T1D may accrue a substantial glycemic load during this period, the authors wrote.

“Patients with early onset of T1D have a high excess risk of premature mortality, cardiovascular [CV] complications, and several life years lost, where poor glycemic control and adverse CV risk factors are associated with poor outcomes,” the researchers said.

Although studies have indicated increased levels of glycated hemoglobin (A1C) occur in adolescent patients or in patients during early adulthood, trajectories for glycemic controls and other CV risk factors by age of onset have yet to be investigated.

To address this knowledge gap and to identify any predicting factors associated with baseline A1C based on age of disease onset, the researchers stratified over 30,000 patients with T1D between the ages of 18 and 75.

Data were gleaned from the Swedish National Diabetes Registry for patients enrolled between January 1998 and December 2012. Patients were broken down into 4 categories based on age of T1D onset: 0 to 10, 11 to 15, 16 to 20, 21 to 25, and 26 to 30 years.

Information regarding CV disease, heart failure, and other additional health complications was amassed from the Swedish Hospital Registry, while demographic data were collected via the Longitudinal Integration Database For Health Insurance And Labour Market Studies.

A total of 32,005 patients with 320,505 registered visits were included in the final analysis. “To calculate risk factor trajectories, mixed linear regression was used and generalized linear mixed model for the outcome of albuminuria, where microalbuminuria and macroalbuminuria were combined into a binary outcome in order to increase power,” the authors wrote. Models were adjusted for sex, groups by age of onset, and other factors.

Among patients aged 25 to 30 years at T1D onset, systolic blood pressure (SBP), body mass index (BMI), frequency of statin use, and the proportion of smokers were slightly higher compared with patients with younger-onset T1D.

Analyses revealed:

• Individuals ≥16 years at onset displayed a relatively low mean A1C level (approximately 55-57 mmol/mol) that gradually increased
• Individuals who received their diagnosis when they were ≤15 years entered adulthood with a mean A1C of approximately 70 mmol/mol
• For all groups, A1C levels stabilized at a mean of approximately 65 mmol/mol by about age 40 years
• In patients who were young at the time of onset, albuminuria appeared at an earlier age, suggesting a more rapid decrease in estimated glomerular filtration rate (eGFR)
• There were no distinct differences in BMI, SBP, and low-density lipoprotein cholesterol (LDL-C) trajectories between groups
• Low education, higher age, and poor risk factor control were associated with higher A1C
• Women displayed slightly higher mean A1C levels, lower eGFR levels, and a flatter LDL-C curve than men, although men seemed to have a slightly higher risk of albuminuria in all age categories

“In this nationwide study, we found substantial differences in mean A1C levels in patients younger than 35 years of age, depending on age at onset, such that onset before the age of 15 was associated with high A1C levels for a long period during early adulthood and an early increase in the probability of albuminuria that suggested a more rapid decline in eGFR,” the authors wrote.

Findings indicate adolescence and early adulthood may be critical periods for improving outcomes for patients with T1D, while treating glycemic levels as aggressively as possible in patients under the age of 16 could reduce the risk of future complications.

However, hormonal changes and social and psychological challenges during puberty could influence patients’ ability to cope with diabetes care management in early adulthood, the researchers noted.

More studies are warranted to determine how to prolong or keep low levels of glucose observed in patients in the first 10 years of follow-up. In addition, “whether lowering of glycemic load specifically for patients with an early onset of T1D will have an impact on the excess risks of late complications and prolong life expectancy should be the subject of further investigation.”

The study was conducted prior to the implementation of continuous glucose monitoring in Sweden, marking a limitation. Data from the day of T1D onset in all patients registered were also unavailable, and some patients had the disease several years prior to inclusion in the database.

Overall, the findings emphasize “the importance of multifaceted medical care, including use of modern technology, for patients with T1D, with a focus on the need for optimizing glycemic control in patients with early-onset diabetes and attempting to mitigate the increase in A1C levels in patients with later-onset disease,” the authors concluded.

Reference:

Edqvist J, Rawshani A, Rawshani A, et al. Trajectories in HbA1c and other risk factors among adults with type 1 diabetes by age at onset. BMJ Open Diabetes Res Care. Published online May 31, 2021. doi:10.1136/bmjdrc-2021-002187