Effect of Formoterol on the Counterregulatory Hormonal Response to Hypoglycemia in Type 1 Diabetes.

Insulin treatment often causes the blood glucose levels to fall too low. The body usually responds to low blood glucose levels by releasing hormones which act against the insulin to help correct the low blood glucose levels. However, this hormone response can be altered in people with diabetes. Currently there are no therapeutic agents that can be used to improve the recovery from hypoglycemia (low blood sugar). The aim of this study is to determine whether a formoterol inhaler can be used to improve and accelerate the recovery from hypoglycemia in patients with type 1 diabetes.

Note: Below is the original detailed description submitted in 2010. The recruitment for this study was stopped at 7 subjects in each study arm. The study design and outcome measures did not change for this study. See below for further details. Original: 15 subjects with well controlled type 1 diabetes and regular hypoglycemia and 15 healthy volunteers will be recruited for this study. If you agree to participate in this study, you will be asked to participate in a screening at Yale New Haven Hospital. Each study subject will undergo two hypoglycemic clamp studies (a procedure where the blood sugar is closely regulated with intravenous insulin and glucose.) In these hypoglycemic clamp studies, the subject will be given an inhaler. On one visit the inhaler will contain formoterol capsules and on the other visit, the subject will be given 'dummy' capsules. Subjects will be required to be admitted to the HRU the night before the study so that glucose levels can be stabilized and hypoglycemia avoided.

The control group were participants without diabetes, matched by sex, age and BMI to the active comparator group.

Glucagon levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages.

Epinephrine levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages

Norepinephrine levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages

Blood glucose levels will be checked every 5 minutes during the 120 minute study session in order to maintain blood glucose levels in the normal and hypoglycemic range. Presented is the average of the collected values.

Inclusion Criteria: type 1 diabetes (well controlled, 2-3 hypoglycemic episodes/wk) age 18-50 BMI 18-30 Exclusion Criteria: pregnancy significant diabetes complications liver disease, cirrhosis cardiac disease neurological disorder autonomic neuropathy kidney disease lactose intolerance

Belfort-DeAguiar RD, Naik S, Hwang J, Szepietowska B, Sherwin RS. Inhaled Formoterol Diminishes Insulin-Induced Hypoglycemia in Type 1 Diabetes. Diabetes Care. 2015 Sep;38(9):1736-41. doi: 10.2337/dc14-2472. Epub 2015 Jul 7.