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Treatment of young patients with HNF1A mutations (HNF1A-MODY)
Insights
Children with HNF1A-MODY diabetes should receive sulfonylurea treatment per guidelines. Many still receive insulin alone, leading to worse control and hypoglycemia risk, contrary to current pediatric diabetes recommendations.
Area of Science:
- Pediatric Endocrinology
- Molecular Genetics
- Diabetes Mellitus
Background:
- Hepatocyte Nuclear Factor 1-Alpha (HNF1A)-Maturity-Onset Diabetes of the Young (MODY) is a genetic form of diabetes.
- Current guidelines recommend oral sulfonylurea treatment for HNF1A-MODY in children and adolescents.
- Deviations from guideline-recommended treatment may impact patient outcomes.
Purpose of the Study:
- To evaluate current treatment practices for HNF1A-MODY in pediatric patients.
- To compare metabolic control and hypoglycemia risk across different treatment modalities.
- To assess adherence to International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines.
Main Methods:
- Analysis of the German-Austrian DPV database including 114 pediatric patients with genetically confirmed HNF1A-MODY.
- Categorization of patients based on treatment: insulin alone, sulfonylurea, meglitinides, or lifestyle.
- Assessment of severe hypoglycemia, HbA1c levels, BMI standard deviation score, serum lipids, and blood pressure.
Main Results:
- Insulin treatment was associated with the highest HbA1c levels (58 mmol/mol) and the highest risk of severe hypoglycemia (3.6 events per 100 patient-years).
- Meglitinide treatment showed the lowest HbA1c (52 mmol/mol) and no severe hypoglycemia.
- Despite guidelines, 40% of medically treated pediatric HNF1A-MODY patients received insulin alone.
Conclusions:
- Insulin monotherapy in pediatric HNF1A-MODY is suboptimal, linked to poorer glycemic control and hypoglycemia risk.
- Non-adherence to ISPAD guidelines, with 40% on insulin alone, suggests potential contributing factors like off-label drug use and treatment inertia.
- Optimizing treatment strategies for HNF1A-MODY in youth is crucial for improved metabolic outcomes.
Aim:
Children and adolescents with a molecular diagnosis of HNF1A-MODY should be treated with oral sulfonylurea according to current International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines.
Methods:
We surveyed the German-Austrian DPV database of 50 043 people and included 114 patients with a confirmed molecular-genetic diagnosis of HNF1A mutation and diabetes onset at below age 18 years. We analysed hypoglycaemic episodes, metabolic control (HbA1c ) and other clinical variables according to treatment groups.
Results:
People with HNF1A-MODY were included and analysed according to treatment with insulin alone (n = 34), sulfonylurea (n = 30), meglitinides (n = 22) or lifestyle (n = 28). In those receiving any drug treatment (n = 86), severe hypoglycaemia did not occur with meglitinide and was highest (at 3.6 events per 100 patient-years) with insulin. HbA1c was highest with insulin treatment (insulin = 58 mmol/mol, 7.5%; sulfonylurea = 55 mmol/mol, 7.2%; meglitinides = 52 mmol/mol, 6.9%; P = 0.008), whereas weight (BMI SD score), serum lipids and blood pressure were not different.
Conclusions:
Of note, 40% of people with HNF1A-MODY and medical treatment were receiving insulin alone and thus were not being treated in line with up-to-date International Society for Pediatric and Adolescent Diabetes/International Diabetes Federation guidelines, despite insulin treatment being associated with worse metabolic control and the risk of hypoglycaemia. The unlicensed use of oral drugs in patients below age 18 years and adherence by both doctors and patients to the initial insulin treatment might contribute to this finding.
