title: Successful maintenance on sulphonylurea therapy and low diabetes complication rates in a HNF1A-MODY cohort.
abstract: HNF1A gene mutations are the most common cause of maturity-onset diabetes of the young (MODY) in the UK. Persons with HNF1A-MODY display sensitivity to sulphonylurea therapy; however, the long-term efficacy is not established. There is limited literature as to the prevalence of micro- and macrovascular complications in this unique cohort. The aim of this study was to determine the natural progression and clinical management of HNF1A-MODY diabetes in a dedicated MODY clinic.
  
  
  
  Sixty patients with HNF1A-MODY and a cohort of 60 BMI-, age-, ethnicity- and diabetes duration-matched patients with Type 1 diabetes mellitus participated in the study. All patients were phenotyped in detail. Clinical follow-up of the HNF1A-MODY cohort occurred on a bi-annual basis.
  
  
  
  Following a genetic diagnosis of MODY, the majority of the cohort treated with sulphonylurea therapy remained insulin independent at 84-month follow-up (80%). The HbA1c in the HNF1A-MODY group treated with sulphonylurea therapy alone improved significantly over the study period [from 49 (44-63) mmol/mol, 6.6 (6.2-7.9)% to 41 (31-50) mmol/mol, 5.9 (5-6.7)%; P = 0.003]. The rate of retinopathy was significantly lower than that noted in the Type 1 diabetes mellitus group (13.6 vs. 50%; P = 0.0001).There was also a lower rate of microalbuminuria and cardiovascular disease in the HNF1A-MODY group compared with the Type 1 diabetes mellitus group.
  
  
  
  This study demonstrates that the majority of patients with HNF1A-MODY can be maintained successfully on sulphonylurea therapy with good glycaemic control. We note a significantly lower rate of micro- and macrovascular complications than reported previously. The use of appropriate therapy at early stages of the disorder may decrease the incidence of complications.
authors.affiliation: Department of Diabetes & Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Bacon
authors.affiliation: Department of Diabetes & Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: M P
authors.initials: MP
authors.lastname: Kyithar
authors.affiliation: Department of Diabetes & Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: S R
authors.initials: SR
authors.lastname: Rizvi
authors.affiliation: Department of Diabetes & Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Donnelly
authors.affiliation: Department of Diabetes & Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: McCarthy
authors.affiliation: Department of Diabetes & Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Burke
authors.affiliation: Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK.
authors.forename: K
authors.initials: K
authors.lastname: Colclough
authors.affiliation: Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK.|Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ellard
authors.affiliation: Department of Diabetes & Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: M M
authors.initials: MM
authors.lastname: Byrne
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000453:epidemiology / Q000209:etiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology; D016022:Case-Control Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000209:etiology; D048909:Diabetes Complications / Q000453:epidemiology* / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000209:etiology; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000209:etiology; D018450:Disease Progression; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D051538:Hepatocyte Nuclear Factor 1-alpha; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; C496487:HNF1A protein, human; C517652:hemoglobin A1c protein, human