Сахарный диабет (May 2022)
Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients
Abstract
BACKGROUND: Monogenic diabetes mellitus (MDM) is a rare form of diabetes mellitus (DM) which caused by one or more mutations in one of the genes that cause pancreatic β-cell dysfunction. Despite the sufficient knowledge of the most common subtypes of MODY, cases of MDM are undiagnosed and classified as type 1 diabetes mellitus and type 2 diabetes mellitus.AIM: To study the clinical, laboratory characteristics, as well as age-related features of GCK-MODY in children.MATERIALS AND METHODS: The studied population is patients with GCK-MODY under the age of 18 years. The diagnosis was confirmed by genetic test, a heterozygous mutation was identificated in the GCK gene.RESULTS: MODY-GCK was verified in 144 patients (131 probands and 13 siblings) under the age of 18 years. Missense mutations were detected in 80.2% (n=105). Mutation was detected in one case in 59.6%. The most common missense mutations were p.G261R (n=7) and p.G258C (n=6). The age of diagnosis of carbohydrate metabolism disorders was 7.6 years [4.0; 11.2]. In 72.2% carbohydrate metabolism disorders were diagnosed accidentally, in 16.7% the examination was provided due to a family history of diabetes, 11.1% had clinical symptoms of diabetes. Fasting glycemia at diagnosis was 6.8 mmol / l [6.4; 7.3], HbA1c — 6.4% [6.1; 6.7]. At examination, the level of fasting glycemia corresponded to normal values in 16.4% of patients, impaired fasting glycemia — in 57.8%, diabetic — in 25.8%. In 62.3% of patients was impaired glucose tolerance, in 18.9% — to diabetic values, and in 11.7% of patients — to a normal level at 120 minutes during the oral glucose tolerance test. A moderate positive correlation was found between the age of examination and the levels of fasting glycemia (r=0.347, p<0.01), C-peptide (r=0.656, p<0.001), and insulin (r=0.531, p<0.001). Insulin resistance (IR) (HOMA index) was detected in 21 patients (14.5%), obesity — in 6 patients (4.2%). In 9 patients (6.25%) was revealed a moderate increase in the titer of specific pancreatic antibodies (AT). The presence of IR, obesity, AT did not affect the level of HbA1c. In 92.3% diet was priscribed, in 4.2% insulin was prescribed, 2.1% — metformin, 1.4% — sulfonylureas.CONCLUSION: In children, disorders of carbohydrate metabolism in GCK-MODY are diagnosed accidentally, asymptomatically at any age from birth, and are characterized by a combination of impaired fasting glycemia and impaired glucose tolerance and, as a rule, do not require antihyperglycemic therapy
Keywords
