What laboratory tests distinguish between Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM)?

From the Guidelines

The most effective approach to diagnose type 1 vs type 2 diabetes involves a combination of clinical assessment, autoantibody testing, and C-peptide measurement, as outlined in the 2024 standards of care in diabetes 1. To differentiate between type 1 and type 2 diabetes, the following laboratory tests are essential:

• Autoantibody testing, including glutamic acid decarboxylase antibodies (GADA), islet tyrosine phosphatase 2 (IA-2), and zinc transporter 8 (ZnT8) antibodies, which are indicative of an autoimmune process characteristic of type 1 diabetes 1.
• C-peptide measurement, which helps distinguish between type 1 (low or undetectable C-peptide) and type 2 diabetes (normal or high C-peptide), reflecting the underlying pathophysiology of insulin deficiency in type 1 and insulin resistance in type 2 1.
• Blood glucose testing, including fasting plasma glucose and HbA1c, is crucial for diagnosing diabetes but does not differentiate between types.
• Assessment of clinical features such as age of onset, BMI, presence of ketoacidosis, and family history can provide additional context but are not definitive on their own. The flowchart for investigation of suspected type 1 diabetes in newly diagnosed adults, as proposed by the 2024 standards of care in diabetes, offers a structured approach to diagnosis, incorporating these elements 1. It is critical to note that while these tests are valuable, the diagnosis and classification of diabetes should be based on a comprehensive evaluation, considering both clinical presentation and laboratory findings, as emphasized in recent guidelines 1.

From the Research

Diagnostic Tests for Type 1 and Type 2 Diabetes

• The diagnosis of diabetes can be made using various tests, including Hemoglobin A1c (HbA1c), fasting plasma glucose, 2-hour postglucose-load plasma glucose, and oral glucose tolerance tests 2.
• HbA1c testing has the advantages of greater clinical convenience, preanalytic stability, and assay standardization, but it should be used in combination with plasma glucose determinations for the diagnosis of diabetes 2.

HbA1c and Plasma Glucose Measurements

• A diagnostic cut-off point of HbA1c ≥ 6.5% misses a substantial number of people with type 2 diabetes, including some with fasting hyperglycemia, and misses most people with impaired glucose tolerance 2.
• Combining the use of HbA1c and plasma glucose measurements for the diagnosis of diabetes offers the benefits of each test and reduces the risk of systematic bias inherent in HbA1c testing alone 2.
• An HbA1c level ≥ 6.0% or fasting plasma glucose ≥ 5.9 mmol/L were the optimal cut-off thresholds for the prediction of the presence of type 2 diabetes in individuals with impaired fasting plasma glucose 3.

Oral Glucose Tolerance Test (OGTT)

• The OGTT is a cornerstone for detecting prediabetes and type 2 diabetes, and the 2-hour post-load glucose (2-h PG) has been the gold standard for defining dysglycemic states 4.
• The 1-hour plasma glucose (1-h PG) during the OGTT is an accurate predictor of type 2 diabetes, with a cutoff of 11.6 mmol/L having a sensitivity of 0.92 and specificity of 0.91 5.
• Measurement of the 1-h PG level could increase the likelihood of identifying high-risk individuals and has the potential to replace the conventional 2-h OGTT, making it more acceptable in the clinical setting 4.

Comparison of Diagnostic Tests

• The choice of diagnostic test depends on various factors, including clinical convenience, preanalytic stability, and assay standardization 2.
• Self-titration of basal insulin at least twice a week with healthcare provider support leads to superior HbA1c reduction in comparison with other strategies, without increasing the risk of severe hypoglycemia 6.
• The use of a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases 5.