TY - JOUR

T1 - Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12)

T2 - Features of clinical course and therapy

AU - Ovsyannikova, Alla K.

AU - Rymar, Oksana D.

AU - Shakhtshneider, Elena V.

AU - Klimontov, Vadim V.

AU - Koroleva, Elena A.

AU - Voevoda, Mikhail I.

N1 - Овсянникова А.К., Рымар О.Д., Шахтшнейдер Е.В., Климонтов В.В., Королева Е.А., Воевода М.И. Сахарный диабет, связанный с мутацией гена ABCC8 (MODY 12): особенности клинического течения и терапии // Сахарный диабет. - 2019. - Т. 22. - № 1. - С. 88-94

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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, microal-buminuria, 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.

AB - 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, microal-buminuria, 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.

KW - ABCC8

KW - Clinical case

KW - MODY diabetes

KW - Molecular-genetic investigation

KW - Mutations

KW - SGLT2 inhibitors

KW - MODY diabetes

KW - mutations

KW - clinical case

KW - ABCC8

KW - molecular-genetic investigation

KW - SGLT2 inhibitors

KW - DOUBLE-BLIND

KW - ONSET

KW - HYPERGLYCEMIA

KW - VARIABILITY

KW - INHIBITOR

KW - VARIANTS

KW - RISK

UR - http://www.scopus.com/inward/record.url?scp=85065127709&partnerID=8YFLogxK

UR - https://www.elibrary.ru/item.asp?id=37307955

U2 - 10.14341/DM9600

DO - 10.14341/DM9600

M3 - Article

AN - SCOPUS:85065127709

VL - 22

SP - 88

EP - 94

JO - Diabetes Mellitus

JF - Diabetes Mellitus

SN - 2072-0351

IS - 1

ER -