Risk factors

Insufficient testing suggested true prevalence of monogenic diabetes is underestimated

Rates of referral for genetic testing for monogenic diabetes need to improve, according to a Victorian study.

A retrospective study of 2,576 referrals to the diabetes clinic at Austin Health between 2018 and 2021 found just 1.8% were referred for genetic testing for suspected maturity onset diabetes of the young (MODY).

The study, published in Diabetes Epidemiology & Management, found of the individuals who proceeded to testing, 37% had a positive genetic test result. A further person showed a genetic variant of unknown significance.

“This suggests that when a clinician clearly suspects a genetic cause of diabetes, a variant is found in more than a third of cases,” the study said.

GCK was the most common variant identified – in four individuals – followed by HNF1A in three individuals, HNF4A in two individuals and INS in one individual.

“3 out of these 4 individuals with GCK-MODY were female and 1 was initially diagnosed with gestational diabetes,” the study said.

It said HNF1A and HNF4A-MODY have a five-fold greater response to sulphonylureas than metformin and nearly a four-fold greater response to sulphonylureas than those with T2DM.

A molecular diagnosis of GCK-MODY allows pharmacological therapy to be discontinued and reduces the need for frequent medical surveillance and complication screening, the researchers said.

“Our results are consistent with previous, showing all of those with GCK, HNF1A and HNF4A variants underwent appropriate treatment changes and glycaemia, reflected by HbA1c, which remained stable over time.”

The INS-MODY case was a 33 year old woman who had been diagnosed with type 1 diabetes at 2 years of age. Her diagnosis was revisited after her own child was diagnosed with monogenic diabetes.

“Although the genetic diagnosis did not alter the treatment of Patient 6’s diabetes, it was important to allow cascade genetic testing of her family members.”

The study said one quarter of patients who declined genetic testing said the cost, at about $AUD 1,100 for next generation sequencing of MODY panel, was prohibitive.

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