What initial investigations should be done for a young adult patient newly diagnosed with Type 1 Diabetes Mellitus (T1DM)?

Initial Investigations for Type 1 Diabetes

For a young adult newly diagnosed with Type 1 Diabetes, start with islet autoantibody testing (GAD antibodies first, followed by IA-2 and ZnT8 if GAD is negative), then screen for associated autoimmune conditions including thyroid antibodies, TSH, and celiac disease markers, along with baseline lipid profile and blood pressure measurement. 1, 2

Diagnostic Confirmation Tests

Islet Autoantibody Panel

• Glutamic acid decarboxylase (GAD) antibodies should be measured first as the primary screening test 1, 2, 3
• If GAD is negative, proceed to IA-2 (islet tyrosine phosphatase 2) antibodies and ZnT8 (zinc transporter 8) antibodies where available 1, 2
• In patients not yet treated with insulin, insulin autoantibodies (IAA) may also be useful 1, 2
• These tests must be performed in an accredited laboratory with established quality control and proficiency testing programs 2
• Note that 5-10% of adult-onset type 1 diabetes cases are autoantibody negative, so negative results in a young adult with acute onset do not exclude the diagnosis 1, 3

C-Peptide Assessment (When Indicated)

• C-peptide testing is particularly useful if the patient is already on insulin therapy to assess residual β-cell function 3, 4
• Do not perform C-peptide testing within 2 weeks of a hyperglycemic emergency, as results will be misleading 2
• Obtain a random (non-fasting) sample within 5 hours of eating with concurrent glucose measurement 3
• Interpretation: <200 pmol/L indicates significant β-cell loss; 200-600 pmol/L is indeterminate; >600 pmol/L suggests preserved function 1, 3

Screening for Associated Autoimmune Conditions

Thyroid Disease Screening

• Measure antithyroid peroxidase (anti-TPO) antibodies soon after diagnosis, as they are more predictive than antithyroglobulin antibodies 1
• Consider measuring antithyroglobulin antibodies as well 1
• Measure TSH when clinically stable or soon after optimizing glycemia (not at initial diagnosis if in DKA or severe hyperglycemia, as results may be misleading due to euthyroid sick syndrome) 1
• If normal, recheck every 1-2 years, or sooner if positive thyroid antibodies or symptoms develop 1
• Rationale: 17-30% of individuals with type 1 diabetes develop autoimmune thyroid disease, and 25% have thyroid autoantibodies at diagnosis 1

Celiac Disease Screening

• Measure IgA tissue transglutaminase (tTG) antibodies with documentation of normal total serum IgA levels soon after diagnosis 1
• If IgA is deficient, measure IgG tTG and deamidated gliadin antibodies instead 1
• Repeat screening within 2 years of diabetes diagnosis, then again after 5 years 1
• Consider more frequent screening if symptoms develop or if there is a first-degree relative with celiac disease 1
• Rationale: Celiac disease occurs in 1.6-16.4% of individuals with type 1 diabetes compared to 0.3-1% in the general population 1

Cardiovascular Risk Assessment

Lipid Profile

• Perform initial lipid profile soon after diagnosis, preferably after glycemia has improved and age is ≥2 years 1
• Initial testing may be done with a non-fasting lipid level with confirmatory testing using a fasting lipid panel 1
• If initial LDL cholesterol is ≤100 mg/dL (≤2.6 mmol/L), repeat testing at 9-11 years of age 1

Blood Pressure Monitoring

• Measure blood pressure at every routine visit 1
• If blood pressure is ≥90th percentile for age, sex, and height (or ≥120/80 mmHg in adolescents aged ≥13 years) on three separate measurements, strongly consider ambulatory blood pressure monitoring 1

Important Clinical Caveats

• Avoid relying solely on A1C for diagnosis in patients with classic symptoms of hyperglycemia or hyperglycemic crisis; use plasma glucose instead (random plasma glucose ≥200 mg/dL is diagnostic with symptoms) 2, 4
• Point-of-care A1C assays should not be used for diagnosis unless FDA-cleared specifically for diagnostic purposes 2
• Approximately one-third of patients with type 1 diabetes present with life-threatening diabetic ketoacidosis 4
• Multiple positive autoantibodies indicate higher risk (70% progression within 10 years) compared to single positive antibody (15% risk) 3
• Other less common autoimmune conditions (Addison disease, autoimmune hepatitis, autoimmune gastritis) should be assessed if clinically indicated 1