Distinguishing Between Type 1 and Type 2 Diabetes Mellitus

Diagnostic Tests

The American Diabetes Association recommends testing for multiple autoantibodies, including Zinc transporter 8 (ZnT8) antibodies, to differentiate between T1DM and T2DM 1
C-peptide measurement assesses endogenous insulin production capacity, with lower levels typically indicating T1DM and higher levels suggesting T2DM 2, 3
For accurate C-peptide results, measure fasting C-peptide when simultaneous fasting plasma glucose is ≤220 mg/dL (12.5 mmol/L) 2, 3

The American Diabetes Association suggests considering autoantibody testing in adults with phenotypic risk factors that overlap with T1DM, such as younger age at diagnosis, unintentional weight loss, ketoacidosis, or rapid progression to insulin dependence 1
The American Academy of Pediatrics recommends considering autoantibody testing in obese children/adolescents presenting with ketosis or ketoacidosis 4, 5
The American Diabetes Association recommends using the AABBCC clinical approach to complement laboratory testing, considering factors such as Age, Autoimmunity, Body habitus, Background, Control, and Comorbidities 1

A diagnosis of T1DM does not preclude having features classically associated with T2DM, such as insulin resistance or obesity 1
Some patients may have features of both T1DM and T2DM, requiring treatment approaches for both conditions 1
C-peptide measurement alone may not be clinically necessary in all cases, as response to therapy can provide useful diagnostic information 3
Insulin or proinsulin testing is not recommended for routine clinical care and is primarily useful for research purposes 6, 3

The American Diabetes Association recommends islet autoantibody testing as the most valuable laboratory test for differentiating between Type 1 and Type 2 diabetes mellitus, particularly in cases where clinical presentation is ambiguous 7
Testing for multiple autoantibodies, including GADA, IA-2A, IAA, and ZnT8A, provides the strongest differentiation between T1DM and T2DM 7, 8
C-peptide measurement assesses endogenous insulin production capacity, with lower levels typically indicating T1DM and higher levels indicating T2DM 9, 10

The European Association for the Study of Diabetes suggests that when clinical presentation is unclear, proceed with antibody testing, and multiple positive autoantibodies strongly suggest T1DM or latent autoimmune diabetes in adults (LADA) 7, 10, 11
In adults with T2DM phenotype but positive autoantibodies (LADA), insulin dependency typically develops over several years 10, 11

The American Diabetes Association recommends that islet autoantibody testing should be performed only in accredited laboratories with established quality control programs 8
Autoantibodies may not be detectable in all T1DM patients and tend to decrease with age 10, 11
The presence of certain HLA-DQB1 alleles may provide additional information as they are mostly protective against T1DM 8