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

Introduction: 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. Objectives: 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 and methods: 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 m$^{2}$), overt proteinuria, blindness, and diabetic foot syndrome. Mutations in the 7 most frequent monogenic diabetes genes were identified using next-generation sequencing. Results: 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 A$_{1c}$ 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/m$^{2}$; and eGFR, 82.2 (12.1) ml/min/1.73 m$^{2}$. 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. Conclusions: 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.