Phenotype Heterogeneity in Glucokinase–Maturity-Onset Diabetes of the Young (GCK-MODY) Patients

Abstract

Objective:The aim of the study was to evaluate the clinical phenotypes of glucokinase-maturity-onset diabetes of the young (GCK-MODY) pediatric patients from Southwest Poland and to search for phenotype-genotype correlations.Methods:We conducted a retrospective analysis of data on 37 CGK-MODY patients consisting of 21 girls and 16 boys of ages 1.9-20.1 (mean 12.5±5.2) years, treated in our centre in the time period between 2002 and 2013.Results:GCK-MODY carriers were found in a frequency of 3% among 1043 diabetes mellitus (DM) patients and constituted the second most numerous group of DM patients, following type 1 DM, in our centre. The mean age of GCK-MODY diagnosis was 10.4±4.5 years. The findings leading to the diagnosis were impaired fasting glucose (IFG) (15/37), symptoms of hyperglycemia (4/37), and a GCK-MODY family history (18/37). Mean fasting blood glucose level was 6.67±1.64 mmol/L. In the sample, there were patients with normal values (4/37), those with DM (10/37), and IFG (23/37). In OGTT, 120 min glucose level was normal in 8, diabetic in 2, and characteristic for glucose intolerance in 27 of the 37 cases. Twelve of the 37 cases (32%) were identified as GCK-MODY carriers. In the total group, mean C-peptide level was 2.13±0.65 ng/mL and HbA1c was 6.26±0.45% (44.9±-18 mmol/mol). Thirty-two patients had a family history of DM. DM autoantibodies were detected in two patients. The most common mutations were p.Gly318Arg (11/37) and p.Val302Leu (8/37). There was no correlation between type of mutations and plasma glucose levels.Conclusion:The phenotype of GCK-MODY patients may vary from those characteristic for other DM types to an asymptomatic state with normal FG with no correlation with genotype.

Screening for monogenic diabetes in primary care

“…Their knowledge regarding the social and family history of the patient can facilitate transferring from insulin to sulphonylureas, thus promoting better quality of life in different ways. [37,38] • Patients taking insulin for years may experience uncertainty, fear, anxiety and excitement on changing to tablets. • Changing from a routine of 2-4 insulin injections a day to tablet therapy improves lifestyle and self-image.…”

“…Oral and insulin treatment are seldom effective and result in a decrease in endogenous insulin production [34,43,44]. Significantly, in cases where therapy with oral hypoglycemic agents or insulin would have been initiated, a molecular diagnosis of GCK MODY leads to cessation of therapy and improvement in quality of life [37].…”

“…In pregnant mothers with HNF1A or HNF4A MODY, sulphonylurea therapy was continued in the past but recognition that sulphonylureas cross the placenta and predispose the fetus to hyperinsulinaemia resulting in macrosomia as well as hypoglycaemia has led to an expert recommendation to switch to insulin pre-pregnancy or in the first trimester during pregnancy [37]. Pearson et al noted that neonates with HNF4A mutations are prone to neonatal hypoglycaemia and macrosomia.…”

Atypical hyperglycemia presentation suggests considering a diagnostic of other types of diabetes: first reported GCK-MODY in Perú

“…Misdiagnosis and unnecessary insulin treatment are commonly used [15]. However, the low doses insulin requirement in a long period of time, more than 06 months, and the absence of DKA diminished the possibility of type 1 diabetes [16]. On the other hand, the age at diagnosis, the absence of relatives with type 2 diabetes and obesity reduce the probability of type 2 diabetes.…”

Maturity Onset Diabetes of the Young in Diabetology Practice

“…Dotychczas opisano kilkanaście genów związanych z MODY. Najczęstszymi postaciami są cukrzyce typu MODY związane z mutacją w genie HNF1α (wątrobowego czynnika transkrypcyjnego 1 alfa) -MODY 3 oraz w genie glukokinazy -MODY 2 (83% u dzieci wszystkich cukrzyc monogenowych) [5,6]. Obraz kliniczny cukrzycy powstającej w wyniku mutacji w genie glukokinazy (MODY 2) różni się od obrazu cukrzyc związanych z defektem genów czynników transkrypcyjnych (np.…”