Successful maintenance on sulphonylurea therapy and low diabetes complication rates in a HNF1A-MODY cohort

Diabet Med. 2016 Jul;33(7):976-84. doi: 10.1111/dme.12992. Epub 2015 Nov 17.


Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / epidemiology
  • Albuminuria / etiology
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Case-Control Studies
  • Coronary Disease / epidemiology
  • Coronary Disease / etiology
  • Diabetes Complications / epidemiology*
  • Diabetes Complications / etiology
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / etiology
  • Diabetic Retinopathy / epidemiology
  • Diabetic Retinopathy / etiology
  • Disease Progression
  • Female
  • Glycated Hemoglobin A / metabolism
  • Hepatocyte Nuclear Factor 1-alpha / genetics*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Maintenance Chemotherapy / methods
  • Male
  • Middle Aged
  • Sulfonylurea Compounds / therapeutic use*
  • Treatment Outcome
  • United Kingdom
  • Young Adult


  • Glycated Hemoglobin A
  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human

Supplementary concepts

  • Maturity-Onset Diabetes of the Young, Type 3