Genetic risk score highlights problem of adult-onset type 1 diabetes
medwireNews: Around two in five cases of type 1 diabetes are diagnosed in patients older than 30 years but may be hard to spot against the background of high type 2 diabetes prevalence, show findings from the UK Biobank.
Researchers used a genetic risk score, based on 29 published risk variants for type 1 diabetes, to categorize 13,250 UK Biobank participants with diabetes according to whether their risk score was above or below the median. There were 1286 more patients with above-median than below-median scores, representing those with genetically defined type 1 diabetes.
In other words, 50% of patients with type 2 diabetes are expected to have above-median scores, whereas almost all patients with type 1 diabetes will do so.
Although 42% of these genetically defined type 1 diabetes cases were diagnosed in people older than 30 years, this represented just 4% of all diabetes cases presenting at this age. By contrast, the 58% of type 1 diabetes cases diagnosed at younger ages accounted for 74% of all diabetes cases in this age group.
“Our findings alert clinicians that type 1 diabetes occurs often after age 30 years, but that it is difficult to detect because of the predominance of type 2 diabetes in older adults,” write Andrew Hattersley (University of Exeter Medical School, UK) and study co-authors in The Lancet Diabetes & Endocrinology.
“A high index of suspicion for type 1 diabetes in later life is important because it has a rapidly progressive phenotype with a substantial risk of diabetic ketoacidosis,” they say, adding that it “should be considered in any middle-aged patient with type 2 diabetes who does not show good glycaemic control on rapidly escalating therapy, especially if they are slim.”
Even among patients diagnosed when they were older than 30 years, those with type 1 diabetes were still younger at diagnosis, at an average of 42 years compared with 52 years for those with type 2 diabetes. They also had a lower BMI, on average, at 27.4 versus 32.4 kg/m2, and 89% had progressed to insulin therapy within 1 year of diabetes, compared with 6% of those with type 2 diabetes. Also, 11% versus just 0.3% had a hospital admission for diabetic ketoacidosis.
In an accompanying commentary, Jose Florez (Massachusetts General Hospital, Boston, USA) applauds the researchers’ “ingenious application of genetics.”
Although cautioning that the genetic risk score cannot be used to diagnose type 1 diabetes, because of the high number of type 2 diabetes patients with above-median scores, he suggests it could be better than autoantibody testing or HLA haplotyping for excluding such a diagnosis.
He also raises the issue of latent autoimmune diabetes of adults (LADA), suggesting that a high type 1 diabetes genetic risk score could also capture LADA patients, making it “a reasonable approximation for all autoimmune diabetes, although this would need to be directly tested in a well phenotyped cohort of patients with LADA.”
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