Mutation search within monogenic diabetes genes in Polish patients with long-term type 1 diabetes and preserved...

Some patients with type 1 diabetes (T1DM) are free from advanced complications despite long‑standing disease. These patients may be carriers of gene mutations responsible for maturity‑onset diabetes of the young and may have been misdiagnosed with T1DM.

We aimed to determine the clinical characteristics of patients with long‑term T1DM, without advanced microvascular complications, and with well‑preserved kidney function. A search for mutations in monogenic diabetes genes was performed.

Patients were recruited at 2 Polish university centers based on the following criteria: T1DM duration of 40 years or longer and absence of advanced complications defined as chronic kidney disease (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 ), overt proteinuria, blindness, and diabetic foot syndrome. Mutations in the 7 most frequent monogenic diabetes genes were identified using next‑generation sequencing.

We enrolled 45 patients with T1DM (mean [SD] age at examination, 59.2 [8.0] years; mean [SD] age at T1DM diagnosis, 14.6 [6.7] years). Mean (SD) hemoglobin A1c levels were 7.6% (1.4%); daily insulin dose, 0.48 (0.17) U/kg; high‑density lipoprotein (HDL) cholesterol levels, 1.9 (0.6) mmol/l; body mass index (BMI), 26.4 (5.0) kg/m2 ; and eGFR, 82.2 (12.1) ml/min/1.73 m2 . Albuminuria and retinopathy were reported in 7 and 39 patients, respectively. We were not able to assign a causative role to any of 10 genetic variants identified by next‑generation sequencing in this cohort.

Patients with long‑term T1DM and preserved kidney function have good glycemic control, elevated HDL cholesterol levels, low insulin requirements, near ‑normal BMI, and a rare occurrence of mutations in monogenic diabetes genes.