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| Topic: |
Diabetes (DM) |
| Title: |
Switching from Insulin to Oral Sulfonylureas in Patients with Diabetes Due to Kir6.2 Mutations. |
| Author: |
Pearson, E.R., et al. |
| Source: |
New England Journal of Medicine. 355(5): 467-477. August 3, 2006. |
| Abstract: |
In diabetes patients diagnosed at six months of age or younger, approximately 30 to 58 percent of cases are caused by heterozygous activating mutations in KCNJ11, encoding the Kir6.2 subunit of the ATP-sensitive potassium channel. These patients present with ketoacidosis or severe hyperglycemia and are treated with insulin. This article reports on a study of glycemic control in 49 patients with Kir6.2 mutations who received appropriate doses of sulfonylureas. The authors also investigated, in smaller subgroups, the insulin secretory responses to intravenous and oral glucose, a mixed meal, and glucagon. A total of 44 patients (90 percent) successfully discontinued insulin after receiving sulfonylureas. Glycated hemoglobin levels improved in all patients who switched to sulfonylurea therapy. Improved glycemic control was sustained at one year. Sulfonylurea treatment increased insulin secretion, which was more highly stimulated by oral glucose or a mixed meal than by intravenous glucose. The authors conclude that sulfonylurea therapy is safe in the short term for patient with diabetes caused by KCNJ11 mutations and is probably more effective than insulin therapy. This pharmacogenetic response to sulfonylureas may result from the closing of the mutant ATP-sensitive potassium channels, thereby increasing insulin secretion in response to incretins and glucose metabolism. 4 figures. 1 table. 30 references. |
| Format: |
Journal Article |
| Language: |
English. |
| Major Keywords: |
Diabetes Mellitus. Genetics. Monogenic Diabetes. Drug Therapy. Pathology. Infants. Insulin. |
| Minor Keywords: |
Pharmacology. Patient Selection. Pancreas. Oral Hypoglycemic Agents. Sulfonylurea Compounds. Administration and Dosage. Glycosylated Hemoglobin. Blood Glucose. |
| Publication Number: |
DMJA12806. |
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