Needle in a Haystack: Type 1 Diabetes Arises Equally in Adulthood

Miriam E Tucker

December 04, 2017

Type 1 diabetes occurs with equal frequency throughout the first 60 years of life, according to newly published data from the UK Biobank.

The investigators determined that onset for 42% of the type 1 cases occurred among individuals ages 31 to 60, while 58% were diagnosed prior to age 30 years. Type 1 diabetes accounted for just 4% of all diabetes cases diagnosed among the adults aged 31 to 60 years, however, meaning it is hard for doctors to pick out those individuals.

"Type 1 diabetes…presents across the first 6 decades of life and should not be considered a disease of children and young adults," Nicholas J Thomas, MRCP, of the Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom, and colleagues write.

And the clinical characteristics of type 1 diabetes among those aged 31 to 60 were similar to those of younger people: They had lower average body mass indexes than type 2 diabetes patients and they progressed rapidly to insulin treatment and had an increased risk for diabetic ketoacidosis.

The findings suggest that clinicians who treat adults should keep type 1 on their radar for patients with diabetes that presents differently from garden-variety type 2, say the researchers.

"Generally be suspicious if tablets fail to improve glucose and symptoms in the first year so they end up on insulin.…The best clue is that they go onto insulin within a year as oral agents fail, especially if they are slim or normal weight," principal investigator Dr Andrew T Hattersley told Medscape Medical News.

He also suggests some tests doctors can do if they are suspicious.      

The findings from the full UK biobank cohort were published November 28 in Lancet Diabetes & Endocrinology by Dr Thomas and colleagues; they had previously reported data from a smaller number of individuals in the database in September 2016 at the European Association for the Study of Diabetes (EASD) 2016 Annual Meeting.

Type 1 Hard to Detect in Adults Among Predominance of Type 2

Dr Thomas and colleagues used a genetic risk score based on 29 common variants to identify 1286 individuals with type 1 diabetes from among a total of more than 13,250 diabetes cases in the Biobank.

"The vast majority of adults with diabetes will have type 2 and not type 1, but the absolute numbers of cases of type 1 is about the same in adults and children," Dr Hattersley stressed. "So, your chance of having type 1 is the same if you are a child or adult, but the chance of type 2 is massively increased in an adult."

And that "massive" preponderance of type 2 in adults is the likely reason that type 1 has long been assumed to be a condition of youth.

"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," the authors write.

But "whatever age it presents, type 1 diabetes is associated with rapid requirement for insulin and risk of ketoacidosis, suggesting that it is not a milder phenotype if diagnosed later in life," they stress.

Biomarkers such as C peptide and islet-specific autoantibodies can be used to assess diabetes type, but neither one alone will make the distinction 100% accurately. The ideal approach is to combine laboratory and clinical features, Dr Hattersley said.

"The best thing is to have a suspicion if [the patient] rapidly goes to insulin and then measure nonrandom fasting C peptide. A value under 600 pmol strongly suggests type 1 and less than 200 pmol/L means [the patient] will need a tpe 1 insulin regime with basal and bolus insulin," he said, adding, "I would test only antibodies — ideally [glutamic acid decarboxylase] and [insulin autoantibody 2] — when there is a high clinical suspicion."

In the future, the Exeter team's genetic risk score might be useful as a rule-out test for type 1 diabetes in the middle-aged group, they say.

While more than 90% with a score in the top half will nonetheless still have type 2 diabetes, those with a score in the bottom half are extremely unlikely to have type 1 diabetes. That score can then be combined with other clinical and laboratory measures to make a definitive diagnosis. 

"The best prediction will combine clinical features, antibodies, and the [type 1 diabetes genetic risk score]," Dr Hattersley said, adding, "We are working on making it generally available, but that is not the case yet."

The study was funded by the Wellcome Trust and Diabetes UK. Dr Thomas is supported by a National Institute for Health Research (NIHR) Academic Clinical Fellowship. Dr Hattersley is supported by a Wellcome Trust Senior Investigator Award and an NIHR Senior Investigator award. Disclosure for  the coauthors are listed in the paper.

Lancet Diabetes Endocrinol. Published November 28, 2017. Article

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