ESPE Abstracts

Background: MODY can be mistaken for Diabetes type 1 or type 2.

Objective: To evaluate genetic background in 22 patients presented with diabetes, negative islet cell antibodies, normal C-peptide and positive family history of diabetes. Genetic testing was done at Invitae laboratory and evaluated 28 genes for diagnosis of MODY.

Results: Patients were divided into 2 groups: Group 1 with a positive genetic test for MODY and Group 2 with a negative. In Group 1 there were 15 patients (21.9 ± 15.3 yrs, 6 females and 6 males, from 5 families and in addition 1 female and 2 males), (4 Caucasians, 3 Hispanics, 8 Asians). In Group 2 there were 7 patients (17.4 ± 4.5 yrs, 4 females, 3 males, 5 Hispanic, 2 Asians) In Group 2 BMI (40 ±8.3), C- peptide (3.8 ± 0.7), SBP 134 ± 15.3, DBP 80.3 ± 7 were higher comparing to Group 1: BMI (29 ± 10.2), C- peptide (1.8 ± 1), SBP 115 ± 15.3, DBP (71.6 ± 9.7). There were no differences in Age, Hb A1c, Cholesterol, Triglycerides, HDl, LDl, ALT, AST between groups. In Group 1, after confirmation of genetic test Insulin treatment was discontinued in 3 cases. 3 patients with HNF4A were treated only with Gluburide 1.25 mg twice a day, 8 patients with Glyburide 20 mg twice a day, Metfromin 850 mg twice a day, and 6 patients with additional Victoza, 1 patient with IER3IP1gene was treated with Insulin and Metformin, 3 patients with GCK MODY 2, didn’t require any treatment. In Group 2, 4 patients were treated with Gluburide 20 mg twice a day, Metfromin 850 mg twice a day and Victoza, and 3 patients with Metfromin and Insulin. In Group 1 Hb A1c significantly improved after treatment from 9.9 ± 2.4 % to 6.8 ± 0.8 (P< 0.001). In Group 2 - no improvement in Hb A1c from 7.5 ±1.9 to 7.6 ± 1.7 %. Heterozygous polymorphism in ABCC8 gene was found in 3 cases from 15 (20%) (Mother, daughter c.2473C>T (P.Arg825Trp)) and 1 boy (c.4280A>T (P.Asp1427Val)), in GCK gene in 4 cases 27 % (father, 2 sons (c.452C>A (P.Ser151Tyr)) and 1 girl (c.1033C>G (P.Arg345Gly)), in GLIS3 gene in 2 cases 13% (mother and son (c.951G>T (P.Glu317Asp)), in HNF1A gene in 2 cases 13%(brother, sister (c.775G>ApV2591)), 3 in HNF4A 20% (2 sisters and father c.224+2T>C in intron 2), 1 in IER3IP1 gene 7 % (c.69C>G (P.His23Gln).

Conclusion: Genetic testing in case of suspected MODY is important because of different responses to treatment.