Switching from Insulin to Oral Sulfonylureas in Patients with Diabetes Due to Kir6.2 Mutations - Lab Report Example

Diabetic patients have a KATP channels with decreased sensitivity to ATP inhibition because of KCNJ11 mutations. As a result of this, their channels remain open in the presence of glucose, thereby reducing insulin secretion. Ketoacidosis or marked hyperglycemia is seen in such patients with low levels of circulating endogenous insulin and are therefore treated with insulin. A class of drugs called Sulfonylureas, close KATP channels by an ATP-independent route, thereby causing insulin secretion.

The authors hypothesized that sulfonylureas may represent a suitable therapy for patients with KCNJ11 mutations. The purpose of the study was to assess i) glycemic control in 49 consecutive patients with Kir6.2 mutations who received appropriate doses of sulfonylureas ii) to investigate the insulin secretory responses to intravenous and oral glucose, a mixed meal, and glucagons in smaller groups and iii) to assay the response of mutant KATP channels to the sulfonylurea tolbutamide in xenopus oocytes.

A total of 49 consecutive patients from 40 families were identified as having diabetes caused by a heterozygous KCNJ11 mutation through sequencing performed in molecular genetics laboratories in Exeter, United Kingdom (34 patients), Paris (5 patients),and Bergen, Norway (10 patients) were the study participants. All 49 patients either switched from insulin to sulfonylurea therapy or were unable to switch but received an adequate dose of sulfonylureas before October 2005 were included in the study.

No other selection criteria were applied. No exclusion criteria were defined by the authors and the study did not include randomization technique. As it was a cohort study, it was not possible to compare the groups. Patients with a successful switch (n =44) had the following mutations F35V, H46Y, R50Q, G53N, G53R, V59M (6 patients), K170T, R201C (5 patients), R201H (23 patients), R201L, E322K, Y330S,