Details

Autor(en) / Beteiligte

• Shepherd, Maggie H.
• Shields, Beverley M.
• Hudson, Michelle
• Pearson, Ewan R.
• Hyde, Christopher
• Ellard, Sian
• Hattersley, Andrew T.
• Patel, Kashyap A.

Titel

A UK nationwide prospective study of treatment change in MODY: genetic subtype and clinical characteristics predict optimal glycaemic control after discontinuing insulin and metformin

Ist Teil von

• Diabetologia, 2018-12, Vol.61 (12), p.2520-2527

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2018

Link zum Volltext

Quelle

SpringerNature Journals

Beschreibungen/Notizen

• Aims/hypothesis Treatment change following a genetic diagnosis of MODY is frequently indicated, but little is known about the factors predicting future treatment success. We therefore conducted the first prospective study to determine the impact of a genetic diagnosis on individuals with GCK -, HNF1A - or HNF4A -MODY in the UK, and to identify clinical characteristics predicting treatment success (i.e. HbA 1c ≤58 mmol/mol [≤7.5%]) with the recommended treatment at 2 years. Methods This was an observational, prospective, non-selective study of individuals referred to the Exeter Molecular Genetic Laboratory for genetic testing from December 2010 to December 2012. Individuals from the UK with GCK - or HNF1A/HNF4A -MODY who were not on recommended treatment at the time of genetic diagnosis, and who were diagnosed below the age of 30 years and were currently aged less than 50 years, were eligible to participate. Results A total of 44 of 58 individuals (75.9%) changed treatment following their genetic diagnosis. Eight individuals diagnosed with GCK -MODY stopped all diabetes medication without experiencing any change in HbA 1c (49.5 mmol/mol [6.6%] both before the genetic diagnosis and at a median of 1.25 years’ follow-up without treatment, p  = 0.88). A total of 36 of 49 individuals (73.5%) diagnosed with HNF1A/HNF4A -MODY changed treatment; however, of the 21 of these individuals who were being managed with diet or sulfonylurea alone at 2 years, only 13 (36.1% of the population that changed treatment) had an HbA 1c ≤58 mmol/mol (≤7.5%). These individuals had a shorter diabetes duration (median 4.6 vs 18.1 years), lower HbA 1c (58 vs 73 mmol/mol [7.5% vs 8.8%]) and lower BMI (median 24.2 vs 26.0 kg/m 2 ) at the time of genetic diagnosis, compared with individuals ( n  = 23/36) with an HbA 1c >58 mmol/mol (>7.5%) (or <58 mmol/mol [<7.5%] on additional treatment) at the 2 year follow-up. Overall, 64% (7/11) individuals with a diabetes duration of ≤11 years and an HbA 1c of ≤69 mmol/mol (≤8.5%) at time of the genetic test achieved good glycaemic control (HbA 1c ≤58 mmol/mol [≤7.5%]) with diet or sulfonylurea alone at 2 years, compared with no participants with a diabetes duration of >11 years and an HbA 1c of >69 mmol/mol (>8.5%) at the time of genetic diagnosis. Conclusions/interpretation In participants with GCK -MODY, treatment cessation was universally successful, with no change in HbA 1c at follow-up. In those with HNF1A/HNF4A -MODY, a shorter diabetes duration, lower HbA 1c and lower BMI at genetic diagnosis predicted successful treatment with sulfonylurea/diet alone, supporting the need for early genetic diagnosis and treatment change. Our study suggests that, in individuals with HNF1A/HNF4A -MODY with a longer duration of diabetes (>11 years) at time of genetic test, rather than ceasing current treatment, a sulfonylurea should be added to existing therapy, particularly in those who are overweight or obese and have a high HbA 1c .