Biomarker Screening Pathway Aids Diagnosis of Monogenic Diabetes

A biomarker screening pathway for monogenic diabetes is an effective and easy approach to systematically screening young-onset patients, according to results of a population-based assessment published in Diabetes Care (2017; doi:10.2337/dc17-0224).


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Monogenic diabetes is often misdiagnosed as type 1 diabetes, leading to unnecessary treatment with insulin. Disease can be confirmed by molecular genetic testing, but this approach tends to be costly. A new screening method for monogenic diabetes is needed to increase the proportion identified from those who choose to undergo genetic testing.

Beverly M Shields, PhD, senior lecturer in medical statistics, Institute of Biomedical and Clinical Science, University of Exeter Medical School (England), and colleagues tested a screening pathway utilizing C-peptide and islet autoantibodies – highly sensitive and specific biomarkers for discerning type 1 diabetes from non-type 1 disease. A total of 1407 patients were sampled from two United Kingdom regions who were diagnosed before age 30 years and currently younger than 50 years.

The biomarker screening pathway consisted of three stages: assessment of endogenous insulin secretion using urinary C-peptide/creatinine ratio (UCPCR); measurement of glutamic acid decarboxylase (GAD) and insulinoma-associated-2 autoantibodies (IA-2A) in the event of demonstrated UCPCR at least 0.2 nmol/mmol; and molecular genetic diagnostic testing for 35 monogenic diabetes subtypes if negative testing for both autoantibodies.

Among the total cohort, 1365 patients had no known cause for their disease, 34 had confirmed monogenic diabetes at baseline, and eight had cystic fibrosis-related diabetes.

Among those with no know genetic cause, 386 (28%) had a UCPCR of at least 0.2 nmol/mmol, 216 of whom were negative for GAD and IA-2A and underwent further genetic testing. Seventeen new cases of monogenic diabetes were diagnosed. The positive predictive value was 20%, indicating a one-in-five successful detection rate for the screening pathway. Negative predictive value was 99.9%.

Researchers concluded that the minimum prevalence of monogenic diabetes in the screening pathway is 3.6% for patients diagnosed aged 30 years or younger. “The biomarker screening pathway for monogenic diabetes is an effective, cheap, and easily implemented approach to systematically screening all young-onset patients,” researchers wrote. However, the most cost-effective approach would likely involve both biomarkers and clinical features, they noted.—Zachary Bessette