Health
Treatment Prevents Hypoglycemia in Children with Hyperinsulinism-ScienceDaily
Researchers at the Philadelphia Children’s Hospital (CHOP) found that the targeted therapies they developed help control blood sugar levels in patients with hyperinsulinosis (HI), a hereditary disorder in which the pancreas produces excess insulin. I showed that it was a target.Survey results announced today Diabetes careProvides further evidence that treatment may prevent hypoglycemia in HI patients and eliminate the need for complete removal of the pancreas, the current standard of care for severe diffuse HI.
“Currently, there are very few treatments for HI, and while these treatments have limited effectiveness, they also have serious side effects,” said Diva, senior research author who heads the endocrine and diabetes department. Dr. D. de Leon Clutchlow, MD, said. Director of the Center for Congenital Hyperinsulinopathy at the Children’s Hospital of Philadelphia. “By targeting the underlying pathophysiology, exendin- (9-39) offers and takes care of potential therapeutic benefits over currently available HI therapies. I am very excited about this study because it can make a big difference in children’s lives. “
Congenital HI is the most common cause of persistent hypoglycemia in infants and children. Although about half of the cases have no known genetic cause, the most common and severe form of HI is caused by mutations in genes encoding two subunits of beta-cell ATP-sensitive potassium channels.ATPHello. Patients with this form of disease are probably due to glucagon in a protein that stimulates amplification of glucagon-like peptide-1 (GLP-1) receptor signaling on beta cells after fasting and a protein-rich diet. I have low blood glucose.
In a previous study, CHOP researchers found that administration of exendin- (9-39), which blocks the GLP-1 receptor, by intravenous infusion significantly increased fasting blood glucose levels in K in adolescents and adults. I showed that.ATPIllness HI form.They also showed that the drug inhibits insulin secretion in the K model.ATPHI disease. Taken together, the results suggest that inhibition of GLP-1 signaling may be an effective means of controlling HI.
Given the success of previous studies, researchers tested Exendin- (9-39) in infants with HI and found that the drug had similar success in the population not only during fasting but also after eating. I decided to check if it fits. They enrolled 16 patients from 10 months to 15 years of age with persistent hypoglycemia due to HI. All but one of them have genetically confirmed K.ATPHello; One patient without genetic confirmation showed symptoms consistent with KATPHello.
To test the efficacy of the treatment, researchers infused three different doses of exendin ((9-39)) for 6 hours after the patient fasted for about 12 hours, and controlled their effects with saline. Compared to the effect of water. Over an additional two days, researchers applied either the highest dose of exendin- (9-39) or saline control solution to a subset of eight patients during a mixed diet resistance test and an oral protein resistance test. I injected it.
Researchers found that exendin- (9-39) reduced the likelihood of fasting hypoglycemia by 76% in the medium-dose group and 84% in the highest-dose group. They found that administration of exendin- (9-39) during a protein challenge reduced the likelihood of hypoglycemia by 82%. The medium dose group also showed a 20% increase in fasting glucose, while the high dose resulted in a 28% increase in postprandial glucose and a 30% increase in glucose after a protein challenge. Notably, the effect of exendin- (9-39) on fasting blood glucose appears to be mediated by suppression of insulin secretion, while the effect on protein-induced hypoglycemia is glucagon exendin- (9-39). 39) May be mediated by increased mediation, suggesting that treatment may induce multiple mechanisms of glycemic control.
“This study provides further evidence to support the use of Exendin- (9-39), which has been given breakthrough therapy designations for the treatment of HI, and has moved this treatment to Phase 3 trials. I’m looking forward to doing it, “said Dr. De León-Crutchlow.
This study was funded by Grant 1R01FD004095-01A1 and the Clifford and Catherine Goldsmith Foundation. The project described was supported by grant number UL1RR024134 from the National Research Resources Center.
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