What genetic testing do physicians use to determine type 2 diabetes?

Genetic Testing for Type 2 Diabetes Diagnosis

Physicians do not use genetic testing to diagnose type 2 diabetes—there is no role for routine genetic testing in people with type 2 diabetes, and such testing should be confined to research settings only. 1

Standard Diagnostic Approach

Type 2 diabetes is diagnosed using biochemical markers of hyperglycemia, not genetic tests. The recommended diagnostic criteria are 1, 2:

• Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) on two separate occasions
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during 75-g oral glucose tolerance test
• HbA1c ≥6.5% (48 mmol/mol) using an NGSP-certified method
• Random plasma glucose ≥200 mg/dL with classic symptoms of hyperglycemia

The fasting plasma glucose test is preferred for screening because it is faster, easier to perform, more convenient for patients, and less expensive than other options. 1, 3

When Genetic Testing IS Indicated

Genetic testing has specific but limited roles in diabetes diagnosis 1:

For Ambiguous Cases Between Type 1 and Type 2

• Genetic markers and genetic risk scores are recommended when patients cannot be clearly classified as having type 1 or type 2 diabetes 1
• This is a moderate-strength recommendation for cases with phenotypic overlap

For Specific Monogenic Diabetes Syndromes

Genetic testing provides valuable diagnostic and treatment information in 1:

• Neonatal diabetes (diagnosed <6 months of age): All infants should have immediate genetic testing, as 80-85% have an underlying monogenic cause 1
• Maturity-Onset Diabetes of the Young (MODY): Testing is recommended for children and young adults with diabetes not characteristic of type 1 or type 2 that occurs in successive generations (autosomal dominant pattern) 1

Specific Genes Tested in Monogenic Diabetes

For MODY and neonatal diabetes, testing targets specific genes 1:

• GCK, HNF1A, HNF4A (most common MODY genes)
• KCNJ11, ABCC8 (KATP channel mutations in neonatal diabetes)
• INS, PDX1, GATA6, EIF2AK3 (other neonatal diabetes genes)

Why Genetic Testing Doesn't Work for Type 2 Diabetes

Type 2 diabetes is a polygenic disease with multiple genetic factors interacting with environmental influences like obesity. 1 Genome-wide association studies have identified more than 30 genetic factors that increase risk, but these risk alleles all have relatively small effects and do not significantly enhance our ability to predict type 2 diabetes risk. 1

Common Pitfalls to Avoid

• Do not order genetic testing for routine type 2 diabetes diagnosis—it provides no clinical value and wastes resources 1
• Do not confuse autoimmune marker testing with genetic testing—islet autoantibodies (like GAD65) are recommended for differentiating type 1 from type 2 diabetes in ambiguous cases, but these are immunologic tests, not genetic tests 1, 4
• Consider monogenic diabetes in atypical presentations—if a patient has antibody-negative diabetes with features not typical of type 1 or type 2 (especially with family history suggesting autosomal dominant inheritance), refer for genetic evaluation 1, 4
• Consultation with a specialized center is recommended when genetic testing is performed to understand the significance of mutations and guide treatment and genetic counseling 1