Islet autoantibody negativity, mild hyperglycemia should trigger MODY genetic screening
medwireNews: Islet autoantibody negativity plus mild hyperglycemia and a family history of diabetes can be used to identify children newly diagnosed with diabetes who should undergo genetic testing for maturity-onset diabetes of the young (MODY), study findings indicate.
“Identifying patients for genetic testing at diabetes diagnosis will prevent delays in the correct molecular genetic diagnosis of patients,” say Claude Marcus (Karolinska Institute, Stockholm, Sweden) and colleagues.
They add: “This will lead to improvements in treatment and quality of life and reductions in treatment and monitoring costs and should be universally advocated in patients with pediatric diabetes at diagnosis.”
The investigators studied a cohort of 3933 children aged 1–18 years (mean 10.1 years) diagnosed with diabetes in Sweden between 2005 and 2010.
Of these, 462 (12%) were negative for autoantibodies against glutamic acid decarboxylase (GAD) antibody, insulinoma antigen-2A, zinc transporter 8A, or insulin.
Among the autoantibody negative participants, 303 underwent genetic testing for the MODY subtypes glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A, and 46 (15%) were diagnosed with MODY.
This equates to a minimal prevalence of 1.2% in the whole cohort, but the researchers estimated that if all autoantibody-negative patients had been genetically tested for MODY, the prevalence would be approximately 1.4%.
Marcus and team found that the key discriminatory clinical feature of MODY was negativity to all four islet autoantibodies, which occurred in 100% of people with MODY versus 11% of those without known MODY.
In addition, patients with MODY had significantly lower mean glycated hemoglobin (HbA1c) levels (7.0 vs 10.7% [53 vs 93 mmol/mol]), plasma glucose levels (11.7 vs 26.7 mmol/L), and rates of diabetic ketoacidosis (0 vs 15%), and were more likely to have a history of parental diabetes (63.0 vs 12.0%).
When the researchers limited genetic testing to the 73 patients who were both autoantibody negative and had an HbA1c level below 7.5% (58 mmol/mol; the previously defined limit for the diagnosis of GCK MODY), the detection rate increased to 49% (36 of 73), with 78% (36 of 46) of the patients with MODY correctly identified.
If the criteria for testing were expanded to include individuals with an HbA1c level below 7.5% or a parent with diabetes, in combination with autoantibody negativity (n=131), the detection rate was 33% (44 of 131), with 96% of the 46 individuals with MODY identified correctly.
Marcus et al also note that at a mean of 5.9 years after initial diabetes diagnosis, the individuals with MODY had “excellent glycemic control,” with a mean HbA1c level of 6.4% (47 mmol/mol), and a low rate of insulin use (9%). Furthermore, 77.8% of the 18 patients on insulin at diagnosis discontinued following a positive genetic test result.
Writing in Diabetes Care, Marcus and co-authors conclude: “At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA1c <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY.”
They add: “It is important to detect MODY, as our results show improved outcome both in terms of insulin cessation and HbA1c.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group