Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC 8 gene: response to appropriate therapy

Autor: Begona Sanchez-Lechuga, Nicholas Ng, S. Clinton, Maria M. Byrne, Kevin Colclough, Marie Burke, F. Reilly, G. Crowe
Rok vydání: 2019
Předmět:
Adult
Blood Glucose
Male
medicine.medical_specialty
Adolescent
Genotype
medicine.drug_class
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Mutation
Missense
030209 endocrinology & metabolism
Sulfonylurea Receptors
Gastroenterology
ABCC8
Young Adult
03 medical and health sciences
0302 clinical medicine
Endocrinology
Diabetes mellitus
Internal medicine
Internal Medicine
medicine
Humans
Hypoglycemic Agents
Insulin
030212 general & internal medicine
Glycated Hemoglobin
Diabetic Retinopathy
C-Peptide
biology
Drug Substitution
business.industry
Incidence (epidemiology)
Glucose Tolerance Test
Middle Aged
medicine.disease
Sulfonylurea
Hypoglycemia
Pedigree
Phenotype
Sulfonylurea Compounds
Diabetes Mellitus
Type 2
Cohort
biology.protein
Phenotype genotype
Female
business
Retinopathy
Zdroj: Diabetic Medicine. 37:876-884
ISSN: 1464-5491
0742-3071
DOI: 10.1111/dme.14145
Popis: Aims To examine the phenotypic features of people identified with ABCC8-maturity-onset diabetes of the young (MODY) who were included in the adult 'Mater MODY' cohort and to establish their response to sulfonylurea therapy. Methods Ten participants with activating ABCC8 mutations were phenotyped in detail. A 2-hour oral glucose tolerance test was performed to establish glycaemic tolerance, with glucose, insulin and C-peptide measurements taken at baseline and 30-min intervals. Insulin was discontinued and sulfonylurea therapy initiated after genetic diagnosis of ABCC8-MODY. A blinded continuous glucose monitoring sensor was used to establish glycaemic control on insulin vs a sulfonylurea. Results The mean age at diagnosis of diabetes was 33.8 ± 11.1 years, with fasting glucose of 18.9 ± 11.5 mmol/l and a mean (range) HbA1c of 86 (51,126) mmol/mol [10.0 (6.8,13.7)%]. Following a genetic diagnosis of ABCC8-MODY three out of four participants discontinued insulin (mean duration 10.6 ± 1.69 years) and started sulfonylurea treatment. The mean (range) HbA1c prior to genetic diagnosis was 52 (43,74) mmol/mol (6.9%) and the post-treatment change was 44 (30,57) mmol/mol (6.2%; P=0.16). Retinopathy was the most common microvascular complication in this cohort, occurring in five out of 10 participants. Conclusions Low-dose sulfonylurea therapy resulted in stable glycaemic control and the elimination of hypoglycaemic episodes attributable to insulin therapy. The use of appropriate therapy at the early stages of diabetes may decrease the incidence of complications and reduce the risks of hypoglycaemia associated with insulin therapy.
Databáze: OpenAIRE
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