Effect of Fasting on Insulin-induced Hypoglycemia Counterregulation in Healthy Humans

Hypoglycemia Clinical Trial

Official title:

Effect of Fasting on Insulin-induced Hypoglycemia Counterregulation in Healthy Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04392843
• Other study ID #: 2018-0625
• Status: Completed
• Phase: N/A
• Start date: April 12, 2019
• Est. completion date: May 11, 2023

Study information

• Verified date: July 2023
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Iatrogenic hypoglycemia is still considered to be the number one barrier to effective glycemic control in patients with type 1 diabetes (T1D). In a previous study, we observed in dogs that liver glycogen content can be a determinant of hormonal and hepatic responses to insulin-induced hypoglycemia. In the experiments described herein, we will determine if nutritionally-manipulated changes in liver glycogen concentrations have an impact on hypoglycemic counterregulation in non-T1D control subjects.

Description:

Because patients with type 1 diabetes (T1D) are required to estimate and administer their own insulin requirements, they frequently overestimate their needs. This often leads to debilitating insulin-induced hypoglycemia, which is the number one barrier to the safe, effective management of glycemia in this population. In addition to the difficulty estimating one's own insulin requirements after a meal, counterregulatory hormone responses to hypoglycemia are impaired in patients with T1D, thereby reducing hepatic glucose production (HGP) and increasing the depth and duration of the hypoglycemic episode.

The discovery of ways by which counterregulatory responses to hypoglycemia can be improved is a priority. In previous experiments in the dog, we observed that experimentally decreasing liver glycogen content (using a 4-hour infusion of glucagon into the hepatic portal vein) reduces counterregulatory hormone secretion during insulin-induced hypoglycemia, thereby reducing hepatic glucose production (HGP). Interestingly, people with T1D have low fasting hepatic glycogen concentrations and the accretion of the sugar in the liver throughout the day is also diminished. Therefore, it is of great interest to understand the relationship between fasting, which would lower liver glycogen levels compared to normal caloric intake, and the counterregulatory responses to insulin-induced hypoglycemia. Furthermore, the translational significance of the investigator's previous findings is also of great importance. To these ends, the studies proposed herein will determine the effect of fasting on hypoglycemic counterregulation in healthy, non-T1D subjects. We hypothesize that fasting will diminish the hormonal and hepatic responses to insulin-induced hypoglycemia.

Each subject will undergo two trials; one where they eat an isocaloric breakfast and lunch prior to an insulin-induced hypoglycemic challenge and a second one during which they remain fasted prior to the hypoglycemic challenge. This study design will allow us to assess the relationship between fasting and the counterregulatory responses to insulin-induced hypoglycemia. For these preliminary studies, only healthy subjects will be studied, thereby reducing their complexity (e.g., no overnight inpatient visits or the need to adjust insulin doses during the feeding periods). Upon completion, we intend to study the more metabolically vulnerable T1D patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 11, 2023
• Est. primary completion date: May 11, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 40 Years

Eligibility

Inclusion Criteria:

• Males and females of any race or ethnicity.

• Aged 21-40 years.

• Fasting glucose lower than 110 mg/dL.

• Non-obese (BMI <28 kg/m2).

• Otherwise healthy as determined by a physician (i.e., no acute or chronic conditions/ illnesses that might have an impact on the results of the study).

Exclusion Criteria:

• Pregnant women.

• Cigarette smoking.

• Taking inflammation-targeting steroids (e.g., prednisone).

• Taking medications targeting adrenergic signaling (e.g., beta-blockers, bronchodilators).

• Hematocrit less than 33%.

• Presence of HIV or hepatitis (due to their deleterious effects on the liver).

• The presence of cardiovascular or peripheral vascular disease.

• The presence of neuropathy, retinopathy or nephropathy.

• A diagnosis of diabetes (type 1 or type 2) or a detection of the presence of any other disease or condition by one of the study doctors, that would be expected to confound the responses to insulin-induced hypoglycemia or make participation in the study dangerous to the individual.

Related Conditions & MeSH terms

• Hypoglycemia

Intervention

Other:
• Fasting
Subjects remain fasted prior to insulin-induced hypoglycemia.
• Feeding
Subjects eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.

Locations

Country	Name	City	State
United States	University of Cincinnati	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
University of Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glucagon	From plasma	During intervention
Primary	Epinephrine	From plasma	During intervention
Primary	Glucose infusion rate	Required to clamp glucose at 50 mg/dL	During intervention
Secondary	Hepatic glucose production	From plasma	During intervention
Secondary	Peripheral glucose uptake	From plasma	During intervention