| First Author | Remedi MS | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 10 | Pages | 2515-22 |
| PubMed ID | 21813803 | Mgi Jnum | J:189272 |
| Mgi Id | MGI:5444821 | Doi | 10.2337/db11-0538 |
| Citation | Remedi MS, et al. (2011) Acute sulfonylurea therapy at disease onset can cause permanent remission of KATP-induced diabetes. Diabetes 60(10):2515-22 |
| abstractText | OBJECTIVE: Neonatal diabetes mellitus (NDM) can be caused by gain-of-function ATP-sensitive K(+) (K(ATP)) channel mutations. This realization has led to sulfonylurea therapy replacing insulin injections in many patients. In a murine model of K(ATP)-dependent NDM, hyperglycemia and consequent loss of beta-cells are both avoided by chronic sulfonylurea treatment. Interestingly, K(ATP) mutations may underlie remitting-relapsing, transient, or permanent forms of the disease in different patients, but the reason for the different outcomes is unknown. RESEARCH DESIGN AND METHODS: To gain further insight into disease progression and outcome, we examined the effects of very early intervention by injecting NDM mice with high-dose glibenclamide for only 6 days, at the beginning of disease onset, then after the subsequent progression with measurements of blood glucose, islet function, and insulin sensitivity. RESULTS: Although approximately 70% of mice developed severe diabetes after treatment cessation, approximately 30% were essentially cured, maintaining near-normal blood glucose until killed. Another group of NDM mice was initiated on oral glibenclamide (in the drinking water), and the dose was titrated daily, to maintain blood glucose <200 mg/dL. In this case, approximately 30% were also essentially cured; they were weaned from the drug after approximately 4 weeks and again subsequently maintained near-normal blood glucose. These cured mice maintain normal insulin content and were more sensitive to insulin than control mice, a compensatory mechanism that together with basal insulin secretion may be sufficient to maintain near-normal glucose levels. CONCLUSIONS: At least in a subset of animals, early sulfonylurea treatment leads to permanent remission of NDM. These cured animals exhibit insulin-hypersensitivity. Although untreated NDM mice rapidly lose insulin content and progress to permanently extremely elevated blood glucose levels, early tight control of blood glucose may permit this insulin-hypersensitivity, in combination with maintained basal insulin secretion, to provide long-term remission. |
