Does Genetic Susceptibility Lead to Late-Onset Type 1 Diabetes?

Having genetic susceptibility to insulin-dependent diabetes is associated with the development of type 1 diabetes (T1D) in adult patients older then 30, according to findings from a cross-sectional analysis published in the Lancet Diabetes & Endocrinology.

Using a genetic risk score, investigators identified white individuals of European descent from the UK Biobank who had a genetic susceptibility to T1D (N=379,511). Researchers then assessed the percentage of patients who had received a diabetes diagnosis within their first 6 decades of life (n=13,250). 

A total of 1286 cases of diabetes were found to be in the half of the UK Biobank population that had high vs low genetic susceptibility to T1D. Approximately 42% of genetically defined T1D cases were in patients who were diagnosed between age 31 and 60, which comprised 4% of all diagnosed diabetes cases older than 30.

 

There were no differences between patients diagnosed with T1D between age 31 and 60 and patients diagnosed younger than age 30 with regard to clinical characteristics. Patients age 31 to 60 diagnosed with T1D did have a significantly lower body mass index (BMI) (27.4 kg/m² [95% CI, 26.7-28.0] vs 32.4 kg/m² [32.2-32.5]; P <.0001), a greater chance of having diabetic ketoacidosis (11% [61/537] vs 0.3% [30/11,696]; P <.0001), and were more likely to use insulin in the first year following diagnosis (89% [476/537] vs 6% [648/11,696]; P <.0001) than patients who were diagnosed with type 2 diabetes.

Volunteer participants in the UK Biobank are generally healthier and come from higher socioeconomic status than the overall UK population, limiting the ability to generalize these findings.

 

In addition to applying to diabetes, screening for genetic susceptibility may also hold potential utility in “other polygenic diseases with strong genetic susceptibility to provide an unbiased population assessment of their contribution to a common phenotype with multiple alternative causes.”

Reference

Thomas NJ, Jones SE, Weedon MN, Shields BM, Oram RA, Hattersley AT. Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank [published online November 30, 2017]. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(17)30362-5