Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes

Abstract

Aims/ hypothesis Late onset type 1 diabetes can be difficult to identify. Measurement of endogenous insulin secretion, using C-peptide, provides a gold standard classification in longstanding diabetes that closely relates to treatment requirements. We aimed to determine the prevalence and characteristics of type 1 diabetes defined by severe endogenous insulin deficiency after age 30 and assess whether these patients are identified and managed as having type 1 diabetes in clinical practice. Methods We assessed the characteristics of type 1 diabetes defined by rapid insulin requirement (within 3 years of diagnosis) and severe endogenous insulin deficiency (non-fasting Cpeptide <200pmol/l) within 583 participants with insulin treated diabetes diagnosed after age 30 from the DARE population cohort. We compared characteristics with participants with retained endogenous insulin secretion (>600pmol/L) and 220 participants with severe insulin deficiency diagnosed under age 30. Results Twenty one percent of participants with insulin treated diabetes diagnosed after age 30 met study criteria for type 1 diabetes. Of these participants, 38% did not receive insulin at diagnosis, of whom 47% self-reported type 2 diabetes. Rapid insulin requirement was highly predictive of severe endogenous insulin deficiency: 85% required insulin within 1 year of diagnosis, and 57% of those progressing to insulin within 3 years of diagnosis had type 1 diabetes. Participants with late onset type 1 diabetes defined by development of severe insulin deficiency had similar clinical characteristics to those with young onset type 1 diabetes. However those with later onset type 1 diabetes had modestly lower type 1 diabetes genetic risk score (0.268 vs 0.279, p<0.001, expected type 2 diabetes population median 0.231), higher islet autoantibody prevalence (GAD, IA2 or ZnT8 positive 78 vs 62% at 13 vs 26 years diabetes duration, p=0.02), and were less likely to identify as having type 1 diabetes (79 vs 100%, p<0.001). Conclusion Type 1 diabetes diagnosed over 30 years of age, defined by severe insulin deficiency has similar clinical and biological characteristics to when occurring at younger ages, but is frequently not identified. Clinicians should be aware that patients progressing to insulin within 3 years of diagnosis have a high likelihood of type 1 diabetes, regardless of initial diagnosis.