ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Lancet 218; 392: 451–530

Despite great improvements in diabetes care, people with type 1 diabetes (T1D) remain at increased risk of mortality and morbidity, in particular from cardiovascular disease (CVD). How exactly diabetes leads to CVD and which factors contribute to the increased risk profile is still largely unknown. Molecular mechanisms are being studied extensively (1). However, simple factors such as age are not considered in current guidelines. This study of the Swedish National Diabetes Register examined how age at diagnosis of T1D influences excess mortality and CVD risk compared to matched controls from the general population.

All patients from Sweden with at least one registration between Jan 1, 1998, and Dec 31, 2012 were included. The authors used Cox regression, with adjustment for diabetes duration, to estimate the excess risks of disease stratified by age at T1D onset (0–10, 11–15, 16–20, 21–25, and 26–30 years). A huge cohort of 27,195 patients with T1D were compared to an even larger number (135,178) of matched controls. 959 patients with T1D and 1501 controls died during follow-up (median duration 10 years).

Patients who developed T1D at a young age (0–10 years) had much higher risks for all-cause mortality (hazard ratio: 4.11; 95% CI 3.24–5.22); CVD mortality (7.38; 3.65–14.94); non-CVD mortality (3.96; 3.06–5.11); CVD events (11.44; 7.95–16.44); coronary heart disease (30.50;(19.98–46.57); acute myocardial infarction (30.95; 17.59–54.45); stroke (6.45; 4.04–10.31); and heart failure (12.90; 7.39–22.51). Corresponding risks for patients who developed T1D in the oldest age group (26–30 years) were 2.83 (95% CI 2.38–3.37) for all-cause mortality, 3.64 (2.34–5.66) for CVD mortality, 2.78 (2.29–3.38) for non-CVD mortality, 3.85 (3.05–4.87) for CVD disease events, 6.08 (4.71–7.84) for coronary heart disease, 5.77 (4.08–8.16) for acute myocardial infarction, 3.22 (2.35–4.42) for stroke, and 5.07 (3.55–7.22) for heart failure. Hence, the excess risks differed by up to 5-times across the diagnosis age groups. The highest overall incidence rate, noted for all-cause mortality, was 1.9 (95% CI 1.71–2.11) per 100 000 person-years for patients with T1D. Sadly, onset of T1D before 10 years of age resulted in a loss of 17.7 life-years (95% CI 14.5–20.4) for women and 14.2 life-years (12.1–18.2) for men.

In summary, young age at onset of T1D is indeed one of the most important determinants of survival, as well as all CVD outcomes. In addition, risk of CVD disease is also gender related, with higher excess risks in women. Even greater care for cardioprotection, such as optimal treatment of hyperlipidemia and hypertension, are warranted in patients with early-onset T1D. Children with T1D are indeed a vulnerable group and need our greatest attention.

Reference: 1. Nurten E, Vogel M, Michael Kapellen T, Richter S, Garten A, Penke M, Schuster S, Körner A, Kiess W, Kratzsch J. Omentin-1 and NAMPT serum concentrations are higher and CK-18 levels are lower in children and adolescents with type 1 diabetes when compared to healthy age, sex and BMI matched controls. J Pediatr Endocrinol Metab. 2018;31:959–969.