Positive islet autoantibodies confirm classical type 1 diabetes in patients treated as type 2 diabetes who have early progression to insulin
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Objective
Early progression to insulin following initial management as type 2 diabetes may indicate missed type 1 diabetes. Recent guidelines advise islet-autoantibody testing in all adults who progress to insulin within 3 years, though this has not been directly tested. We aimed to determine whether positive islet autoantibodies in this setting confirm the genetic characteristics and C-peptide progression of classical type 1 diabetes.
Research Design and Methods
We compared genetic susceptibility to type 1 and type 2 diabetes (T1DGRS and T2DGRS) and prospectively assessed C-peptide loss over 3 years after diagnosis among islet-autoantibody-positive adults initially treated as having type 2 diabetes (without insulin) who progressed to insulin within 3 years (n=86), versus participants with classical type 1 (n=499) and type 2 (n=603) diabetes. Results were replicated in cross-sectional data from the DARE/GoDARTS studies (n=9466).
Results
Participants who progressed to insulin within 3 years and had positive islet autoantibodies had the genetic characteristics and C-peptide loss of classical type 1 diabetes: T1DGRS −0.04 (−0.27, 0.18) vs 0.00 (−0.09, 0.09) [p=0.71], T2DGRS −0.35 (−0.59, −0.11) vs −0.35 (−0.44, −0.26) [p=0.99] and annual change in urine C-peptide creatinine ratio −47% (−55%, −40%) vs −49% (−52%, −46%) [p=0.6] respectively. In contrast, autoantibody-positive participants without early insulin (n=51) had genetic and C-peptide characteristics consistent with type 2 diabetes. Findings were similar in cross-sectional cohorts.
Conclusion
Islet-autoantibody-positive individuals with early insulin requirement following initial treatment as type 2 diabetes have similar genotype and progression to classical type 1 diabetes. This supports recent guidance that they should be diagnosed and treated as type 1 diabetes.
Graphical Abstract
Article highlights
Why did we undertake this study?
Recent international clinical guidelines have suggested that patients initially thought to have type 2 diabetes who progress to insulin within 3 years should have islet antibody testing, and that in this setting, positive islet autoantibodies will confirm classical type 1 diabetes. The guidelines are based on the mathematical interpretation of islet-autoantibody test performance and have not been directly tested.
What is the specific question(s) we wanted to answer?
Does a positive islet autoantibody test in people initially treated as having type 2 diabetes (without insulin) who progress to insulin within 3 years of diagnosis identify those with the genetic characteristics and C-peptide loss seen in classical type 1 diabetes?
What did we find?
In prospective analysis from diagnosis, we found that individuals initially treated as type 2 diabetes who progressed to insulin within 3 years of diagnosis and had one or more positive islet autoantibodies had similar genetic susceptibility to type 1 diabetes, and rate of C-peptide loss over 3 years, as individuals with classical type 1 diabetes. In contrast, the genetic susceptibility and rate of C-peptide loss in participants autoantibody positive without insulin requirement were largely similar to antibody-negative type 2 diabetes. Findings were similar in the analysis of two cross-sectional studies.
What are the implications of our findings?
Our results support routine islet autoantibody testing in patients initially thought to have type 2 diabetes who require insulin within 3 years and suggest that individuals who test positive should be classified and managed as classical type 1 diabetes, in line with recent international guidelines.
