Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients
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...
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Endocrinology Research Centre
2022-05-01
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| Series: | Сахарный диабет |
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| Online Access: | https://www.dia-endojournals.ru/jour/article/view/12819 |
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| author | E. A. Sechko T. L. Kuraeva L. I. Zilberman D. N. Laptev O. B. Bezlepkina V. A. Peterkova |
| author_facet | E. A. Sechko T. L. Kuraeva L. I. Zilberman D. N. Laptev O. B. Bezlepkina V. A. Peterkova |
| author_sort | E. A. Sechko |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-03-08T15:18:53Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-0351 2072-0378 |
| language | English |
| last_indexed | 2025-03-14T16:34:46Z |
| publishDate | 2022-05-01 |
| publisher | Endocrinology Research Centre |
| record_format | Article |
| series | Сахарный диабет |
| spelling | doaj.art-0a1ea31930b74524921be7eafbdbe3102025-02-21T09:29:38ZengEndocrinology Research CentreСахарный диабет2072-03512072-03782022-05-0125214515410.14341/DM1281910938Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patientsE. A. Sechko0T. L. Kuraeva1L. I. Zilberman2D. N. Laptev3O. B. Bezlepkina4V. A. Peterkova5Endocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreBACKGROUND: 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 therapyhttps://www.dia-endojournals.ru/jour/article/view/12819gck genemonogenic diabetes mellitusmodyhyperglycemia in childrendiabetes mellitus in children and adolescents |
| spellingShingle | E. A. Sechko T. L. Kuraeva L. I. Zilberman D. N. Laptev O. B. Bezlepkina V. A. Peterkova Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients Сахарный диабет gck gene monogenic diabetes mellitus mody hyperglycemia in children diabetes mellitus in children and adolescents |
| title | Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients |
| title_full | Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients |
| title_fullStr | Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients |
| title_full_unstemmed | Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients |
| title_short | Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients |
| title_sort | non immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene gck mody data of 144 patients |
| topic | gck gene monogenic diabetes mellitus mody hyperglycemia in children diabetes mellitus in children and adolescents |
| url | https://www.dia-endojournals.ru/jour/article/view/12819 |
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