A pair of research studies has shed light on the benefits of screening children for type 1 diabetes at a young age.
Children with early-stage type 1 diabetes progress to clinical diabetes at a similar rate, regardless of whether they have a first-degree family history of the condition.
That’s according to the German research team behind a population-based screening study of almost 220,000 children, which ran over a 10-year period.
“Critical gaps remain regarding stage-specific prevalence, progression rates, and the natural history of type 1 diabetes in children without increased genetic risk, information that is required for optimising screening strategies, counselling families, and guiding therapeutic deployment,” the researchers wrote in JAMA.
“Initiated in 2015, the Fr1da study has conducted 10 years of screening to detect and monitor early-stage type 1 diabetes. The objectives of the current analysis are to provide the frequency and disease prognosis of an early-stage type 1 diabetes diagnosis in a general paediatric population.”
Primary care paediatricians located in Bavaria, Germany, who had registered to be part of the study invited children they treated who had not been diagnosed with clinical diabetes to participate in islet autoantibody screening as part of their regular checkups.
If the screening revealed two or more islet autoantibodies, the paediatrician was notified and an additional blood sample was taken to confirm early-stage type 1 diabetes.
The children and their families were invited to attend a specialist paediatric diabetes centre throughout the region for monitoring and follow-up – including metabolic staging using an oral glucose tolerance test and HbA1c measurement on a regular basis – while families who declined staging were monitored in a similar fashion by their primary care clinician.
There were 219,951 children screened during the study (48.7% female, median age of 3.1 years), which represented 17% of the estimated number of children who were eligible to participate. Of these, 730 (0.33% of the entire sample) were found to have two or more islet autoantibodies.
Thirty-three of these participants (4.5%) were diagnosed with stage 3 type 1 diabetes before providing a confirmatory blood sample and were therefore excluded, while a further 67 children were excluded for not providing a confirmatory sample.
Of the 630 remaining children, 590 (93.7%) were again positive for two or more islet autoantibodies and deemed to have early-stage type 1 diabetes.
Multivariable modelling suggested that the relative risk of having early-stage type 1 diabetes increased with age (RR and 95% confidence interval 1.70 [1.36-2.55] for children aged six years and older compared to children under the age of three) was higher in children with a first-degree relative with type 1 diabetes (4.80 [3.85-5.93]), and in children with obesity (1.50 [1.11-1.98] compared to children of a normal weight).
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Most of the children confirmed to have early-stage type 1 diabetes (491/590) participated in metabolic staging, with 366 having stage 1 type 1 diabetes, 87 having stage 2 type 1 diabetes, and 18 as having stage 3 type 1 diabetes.
Two hundred and sixty of the screened children went on to develop clinical diabetes over a median follow-up of 5.7 years; 212 of these came from the 590 children diagnosed with early-stage type 1 diabetes at the initial screening, while 48 children without an early-stage diagnosis going on to develop clinical diabetes.
“In total, 619 participants were diagnosed with early-stage (stage 1 or 2) type 1 diabetes in the first and second screens,” the researchers wrote.
“The cumulative progression to clinical diabetes (stage 3) was 36.2% (95% CI, 31.2%-40.8%; 156 cases) at five years of follow-up, with an annualized rate of 9.6%.”
“The risk did not differ significantly between children with and without a first-degree relative with type 1 diabetes (5-year risk, 41.4% [95% CI, 27.9%-52.4%]; 28 cases, vs 35.3% [95%CI, 29.9%-40.2%]; 128 cases).”
However, the presence of the IA-2A antibodies was associated with an increased rate of progression towards clinical diabetes (hazard ratio 2.32, 1.39-3.61), while the GADA autoantibodies seemed were associated with a slower rate (0.51, 0.33-0.80).
“These findings inform disease-modifying therapy trials and suggest that screening can be considered beyond genetically selected populations,” the German research team concluded.
The importance of diagnosing type 1 diabetes in children early has been highlighted further by the findings of an Australian registry-based population study, which reported that children with an onset of diabetes before they turned seven years old had a lower risk of chronic complications over the following two decades compared to children with an age of onset beyond seven years. The Australian findings were published in Diabetes Care.
Researchers from the University of Sydney analysed data for 5202 people from New South Wales who were diagnosed with type 1 diabetes before the age of 16. Data from hospital, ED, public insurance, and death-related datasets were linked to provide up to 30 years of follow-up for included individuals.
Roughly a third of participants (32.6%) received their diagnosis before age seven, with 48.8% diagnosed between seven and 12 years of age and 18.6% diagnosed between 13 and 16 years. Kidney-related complications (53.4 per 10,000 person-years) were more common than cardiac complications (9.2 per 10,000) in the first two decades after the onset of diabetes.
After accounting for factors including the year of diabetes diagnosis, sociodemographic factors, and the presence of acute diabetes complications, children diagnosed before the age of seven were 68% less likely to experience cardiac complications in the two decades following diagnosis compared to children diagnosed between age 13 and 16 (adjusted hazard ratio and 95% confidence interval 0.32, 0.15-0.69).
Similar associations were observed for a younger age at diagnosis and severe retinopathy (0.25, 0.17-0.36), vascular complications in the lower limb (0.41, 0.24-0.69), peripheral neuropathy (0.16, 0.08-0.32), and kidney complications (0.40, 0.30-0.53).
“Children with type 1 diabetes onset before age seven…had lower chronic complication risk in the first 20 years postdiagnosis, supporting a slower time to develop complications with prepubertal onset,” the researchers concluded.
