Clinical factors predict good glycemic control after MODY treatment switch
medwireNews: Baseline glucose control, diabetes duration, and BMI all impact whether an individual achieves optimal glucose control after a genetic diagnosis and treatment change for maturity onset diabetes of the young (MODY), UK researchers report.
Maggie Shepherd (University of Exeter) and colleagues found that, in their study, 73.5% of 49 individuals diagnosed with HNF1A/HNF4A-MODY changed treatment following their genetic diagnosis, including 21 who switched to diet (n=3) or sulfonylureas (n=18) alone, in line with current guidelines.
Of these, 13 (61.9%) had good glycemic control, defined as glycated hemoglobin (HbA1c) at or below 7.5% (≤58 mmol/mol) at 2 years.
However, the researchers point out that although the majority of individuals who switched to diet or sulfonylureas alone achieved good glycemic control, they actually only accounted for 36.1% of the total HNF1A/HNF4A-MODY population who switched treatment.
This could be due to “clinical inertia or limited experience among local clinicians in managing HNF1A/HNF4A-MODY,” previous recommendations to try sulfonylureas even among individuals with longstanding diabetes, or a lack of standardised guidelines for individuals needing additional second-line therapy, Shepherd et al remark.
Of note, individuals with HNF1A/HNF4A-MODY who achieved good glycemic control with diet or sulfonylureas alone had a significantly shorter median diabetes duration (4.6 vs 18.1 years), lower median BMI (24.2 vs 26.0 kg/m2), and lower HbA1c (7.5 vs 8.8%) at the time of genetic diagnosis than those who did not, a finding which the researchers believe supports “the need for early genetic diagnosis and treatment change.”
And when the investigators combined the effect of diabetes duration and HbA1c at HNF1A/HNF4A-MODY diagnosis, they found that 64% of individuals who had diabetes for 11 years or less and an HbA1c no higher than 8.5% (69 mmol/mol) at the time of the genetic test achieved good glycemic control at 2 years with diet or sulfonylurea treatment alone, compared with none of those with a longer diabetes duration and higher HbA1c level.
They chose these cutoffs as they were the median values for the HNF1A/HNF4A-MODY cohort, and similar results were observed when diabetes duration was combined with normal versus overweight or obese BMI (cutoff = 25 kg/m2).
“As a consequence of these data, we now recommend that a sulfonylurea should be added to existing treatment, rather than replacing it, in individuals with HNF1A/HNF4A-MODY with a longer diabetes duration (>11 years), especially in those with higher HbA1c levels at genetic diagnosis and a BMI >25 kg/m2,” Shepherd et al write in Diabetologia.
The authors also report that eight of nine individuals with GCK-MODY stopped all diabetes medication following their genetic diagnosis.
Following treatment cessation, the researchers observed no change in HbA1c among the individuals with GCK-MODY; it remained at the pre-genetic diagnosis level of 6.6% (49.5 mmol/mol) during a median 1.25 years of follow-up.
They say this finding highlights “the significance of identifying individuals with GCK-MODY as diabetes medication is unnecessary and follow-up is not required.”
By Laura Cowen
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