Providing information for patients and professionals on research and clinical care in genetic types of diabetes.

Guidance for transferring HNF1A or HNF4A patients from insulin to sulphonylureas

This approach would be appropriate for patients with a confirmed mutation in HNF1A or HNF4A who have not previously progressed from diet, to sulphonylureas to insulin and with no previous history of ketoacidosis. Often these patients have been on insulin from diagnosis, in such cases we advise checking that both GAD and IA2 pancreatic antibodies are negative prior to transfer. These tests can be performed by the Exeter laboratory on request. Further details available here. Some evidence of non insulin dependent diabetes is also helpful (but not essential), for example: a C-peptide measurement indicating the patient is producing some insulin of their own or patient’s own report of missing insulin for approx 3 days with no problem. We are able to measure urinary c-peptide creatinine ratio (UCPCR) in Exeter. Post prandial urine samples should be collected into boric acid containers (35ml MSU pot, red top) and posted via your local laboratory to Clinical Chemistry, Area A2, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW Further details for UCPCR Analysis.

Prior to transfer

The patient should be advised this is a ‘trial’ off insulin and if unsuccessful, insulin will need to be recommenced. As HNF1A is progressive insulin treatment is likely to be needed again in the future. Transfer off insulin is likely to be most successful in younger patients (Transfer from insulin to sulphonylureas Insulin should be stopped and Gliclazide 40mg commenced (20mg Gliclazied could be the starting dose for slim adolescents and 80mg Gliclazide could be the starting dose for those who have had diabetes >20 years). The dose should be increased as necessary. Patients with HNF1A who have transferred from insulin successfully to date are currently managed on between 20mg and 320mg Gliclazide. We recommend daily contact with a Diabetes Specialist Nurse (DSN) initially for support and dosage adjustment. This may be the Genetic Diabetes Nurse in your area, or your own DSN supported by the Exeter team. The patient should be asked to test their blood glucose 4 times a day initially and test their urine for ketones. Please warn the patient about the possibility of hypoglycaemia on this treatment.

Follow up

We recommend that HbA1c levels be repeated at 3 monthly intervals. If this regime fails to control BG levels as indicated by a rise in HbA1c of 1% or more from that last recorded on insulin or the presence of hyperglycaemic symptoms then patients should be recommenced on insulin dose. The use of long acting insulin in combination with sulphonylureas could be considered. Glycosuria in HNF1A patients is likely as HNF1A patients have a low renal threshold.

Further information

For specific advice regarding individual patients please contact: Maggie Shepherd on +44 (0) 1392 40 8261 or Professor Andrew Hattersley on +44 (0) 1392 40 8260

Also see the following articles:

1. M Shepherd, ER Pearson, J Houghton, G Salt, S Ellard, AT Hattersley. 2003. No deterioration in glycemic control in HNF1a maturity onset diabetes of the young following transfer from long term insulin to sulphonylureas. Diabetes Care 26(11):3191-3192

2. M Shepherd. 2003. "I’m amazed I’ve been able to come off injections": Patient’s perceptions of genetic testing in diabetes. Practical Diabetes International 20(9):338-343