Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapy
Maturity-Onset Diabetes of the Young (MODY) is a heterogeneous group of diseases associated with genes mutations leading to dysfunction of pancreatic β-cells. Among the 14 identified MODY variants, MODY 1–5 are the most studied. The article reports a MODY 12 clinical case, with mu...
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| Format: | Article |
| Language: | English |
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Endocrinology Research Centre
2019-03-01
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| Series: | Сахарный диабет |
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| Online Access: | https://www.dia-endojournals.ru/jour/article/view/9600 |
| _version_ | 1826588058532708352 |
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| author | Alla K. Ovsyannikova Oksana D. Rymar Elena V. Shakhtshneider Vadim V. Klimontov Elena A. Koroleva Mikhail I. Voevoda |
| author_facet | Alla K. Ovsyannikova Oksana D. Rymar Elena V. Shakhtshneider Vadim V. Klimontov Elena A. Koroleva Mikhail I. Voevoda |
| author_sort | Alla K. Ovsyannikova |
| collection | DOAJ |
| description | Maturity-Onset Diabetes of the Young (MODY) is a heterogeneous group of diseases associated with genes mutations leading to dysfunction of pancreatic β-cells. Among the 14 identified MODY variants, MODY 1–5 are the most studied. The article reports a MODY 12 clinical case, with mutation in ABCC8, encoding the sulphonylurea receptor. Diabetes mellitus manifested in a 27-year-old man with hyperglycaemia up to 24 mmol/L, without ketosis. Non-proliferative diabetic retinopathy, microalbuminuria, dyslipidaemia and carotid atherosclerosis were revealed upon initial examination. The levels of pancreatic islet cell antibodies and glutamate decarboxylase antibodies were negative, while the level of C-peptide was within the normal range. Insulin therapy in the basal-bolus regimen was provided with a gradual dose reduction due to frequent hypoglycaemia. The preproliferative retinopathy with macular oedema was revealed after 4 months of therapy, and panretinal photocoagulation of both eyes was performed. A molecular genetics study revealed a mutation in the gene ABCC8, the same mutation was found in patient’s mother and uncle. Insulin therapy was cancelled, and the treatment of gliclazide MR 60 mg/day was initiated, which resulted in extreme glycaemic excursions. Thereby, sodium–glucose cotranporter-2 (SGLT2) inhibitor dapagliflozin 10 mg/day was added. A reduction in glucose variability parameters were observed on combination therapy. After 6 months till 1.5 years of treatment, glycaemic control was optimal, no hypoglycaemic episodes were observed. This case study demonstrates clinical features of MODY 12, and the potential of combination of sulfonylurea and SGLT2 inhibitor in the treatment of this disease. |
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| format | Article |
| id | doaj.art-948b836d2f294e77b3cc083993c40b71 |
| institution | Directory Open Access Journal |
| issn | 2072-0351 2072-0378 |
| language | English |
| last_indexed | 2025-03-14T16:35:18Z |
| publishDate | 2019-03-01 |
| publisher | Endocrinology Research Centre |
| record_format | Article |
| series | Сахарный диабет |
| spelling | doaj.art-948b836d2f294e77b3cc083993c40b712025-02-21T09:29:35ZengEndocrinology Research CentreСахарный диабет2072-03512072-03782019-03-01221889410.14341/DM96008643Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapyAlla K. Ovsyannikova0Oksana D. Rymar1Elena V. Shakhtshneider2Vadim V. Klimontov3Elena A. Koroleva4Mikhail I. Voevoda5<p>Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences; Novosibirsk State University</p><p>Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences</p><p>Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences</p><p>Novosibirsk State University; Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences</p><p>Novosibirsk State University; Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences</p><p>Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences; Novosibirsk State University</p>Maturity-Onset Diabetes of the Young (MODY) is a heterogeneous group of diseases associated with genes mutations leading to dysfunction of pancreatic β-cells. Among the 14 identified MODY variants, MODY 1–5 are the most studied. The article reports a MODY 12 clinical case, with mutation in ABCC8, encoding the sulphonylurea receptor. Diabetes mellitus manifested in a 27-year-old man with hyperglycaemia up to 24 mmol/L, without ketosis. Non-proliferative diabetic retinopathy, microalbuminuria, dyslipidaemia and carotid atherosclerosis were revealed upon initial examination. The levels of pancreatic islet cell antibodies and glutamate decarboxylase antibodies were negative, while the level of C-peptide was within the normal range. Insulin therapy in the basal-bolus regimen was provided with a gradual dose reduction due to frequent hypoglycaemia. The preproliferative retinopathy with macular oedema was revealed after 4 months of therapy, and panretinal photocoagulation of both eyes was performed. A molecular genetics study revealed a mutation in the gene ABCC8, the same mutation was found in patient’s mother and uncle. Insulin therapy was cancelled, and the treatment of gliclazide MR 60 mg/day was initiated, which resulted in extreme glycaemic excursions. Thereby, sodium–glucose cotranporter-2 (SGLT2) inhibitor dapagliflozin 10 mg/day was added. A reduction in glucose variability parameters were observed on combination therapy. After 6 months till 1.5 years of treatment, glycaemic control was optimal, no hypoglycaemic episodes were observed. This case study demonstrates clinical features of MODY 12, and the potential of combination of sulfonylurea and SGLT2 inhibitor in the treatment of this disease.https://www.dia-endojournals.ru/jour/article/view/9600mody diabetesmutationsclinical caseabcc8molecular-genetic investigationsglt2 inhibitors |
| spellingShingle | Alla K. Ovsyannikova Oksana D. Rymar Elena V. Shakhtshneider Vadim V. Klimontov Elena A. Koroleva Mikhail I. Voevoda Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapy Сахарный диабет mody diabetes mutations clinical case abcc8 molecular-genetic investigation sglt2 inhibitors |
| title | Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapy |
| title_full | Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapy |
| title_fullStr | Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapy |
| title_full_unstemmed | Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapy |
| title_short | Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapy |
| title_sort | diabetes mellitus associated with the mutation of the abcc8 gene mody 12 features of clinical course and therapy |
| topic | mody diabetes mutations clinical case abcc8 molecular-genetic investigation sglt2 inhibitors |
| url | https://www.dia-endojournals.ru/jour/article/view/9600 |
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