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

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Abstract

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.

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