Endocrine Abstracts

Introduction

Maturity Onset Diabetes of the Young (MODY) type 1 is characterized by mutations in hepatocyte nuclear factor 4a (HNF4a) gene, leading to progressive dysfunction of pancreatic beta-cells with optimal response to sulphonylurea treatment. However, most of these patients are initially misdiagnosed as having type 1 diabetes and inappropriately treated with insulin. Data on adequate transferring from insulin to sulphonylureas following genetic diagnosis in this setting is limited.

Case

We report the case of a 45 year-old male with a so-called type 1 diabetes, diagnosed at 10 years-old. He was under metformin and glibenclamide for twelve years, and then insulin therapy was initiated. He was not overweight and presented significant family history of diabetes: mother, grandmother, father and a 12 year-old daughter (diagnosed two years ago, under insulin regimen). Further investigation revealed negative pancreatic antibodies, low C-peptide and poor metabolic control throughout the years, with diabetic retinopathy. Given these data, genetic testing for MODY was performed and identified a heterozygous missense variant of HNF4a gene (c.602A > C, p.His201Pro), recently described in the literature (also found in his daughter). In December/2020, he was under an intensive basal-bolus insulin regimen (insulin detemir 14 units twice daily and insulin glulisine before meals; total daily dose 34 units, body weight 75.4 kg). Laboratory workup showed glucose 274 mg/dl, C-peptide 0.37 ng/ml (0.81–3.85), HbA1c 8.5%. Flash glucose monitoring system revealed estimated A1c 9.1% and marked glycemic variability: 67% above target, 32% in target and 1% below. Transferring of treatment was performed under medical surveillance: we stopped rapid-acting insulin, maintained long-acting insulin dosage and started gliclazide 80 mg/day. Close patient monitoring was maintained and three weeks later he presented a much more stable glycemic pattern with estimated A1c 7.6% and glucose values 37% above target, 63% in target and 0% below. Basal insulin was reduced to 20 units/day and gliclazide dose increased to 120 mg, with continuous glycemic improvement (estimated A1c 7.0%), on ongoing monitoring.

Discussion

Recent data on HNF4a-MODY suggests that sulphonylurea should be added to existing insulin therapy, rather than replacing it, in subjects with longer duration of diabetes who are overweight and have high HbA1c at the time of genetic diagnosis, as found in our case. Nonetheless, this commonly forgotten diagnosis should be seeked, given that treatment change could have significant clinical impact, with improvement of glycemic control and patient quality of life (as a pill replaced three insulin injections per day).