Effect of Fasting on Hypoglycemic Counterregulation in Type 1 Diabetes

Sponsor

University of Cincinnati (Other)

Overall Status

Recruiting

CT.gov ID

NCT05973799

Collaborator

(none)

Enrollment

Location

Arms

62.7

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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, it was observed in people without diabetes that fasting can be detrimental to the hormonal and hepatic responses to insulin-induced hypoglycemia. In the experiments described herein, the impact fasting has on hypoglycemic counterregulation in people with T1D will be determined.

Condition or Disease	Intervention/Treatment	Phase
Hypoglycemia type1diabetes	Other: Fasting Other: Feeding	N/A

Detailed 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 in people with T1D is a priority. In previous experiments, it was observed that fasting reduces counterregulatory hormone secretion in healthy humans during insulin-induced hypoglycemia, thereby reducing hepatic glucose production (HGP). Therefore, the studies proposed herein will determine the effect of fasting on hypoglycemic counterregulation in people with T1D. It is hypothesized 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 assessment of the relationship between fasting and the counterregulatory responses to insulin-induced hypoglycemia in a population that is particularly vulnerable to low blood sugar.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Each subject will undergo two metabolic studies, one after having remained fasted and one after having eaten breakfast and lunch.Each subject will undergo two metabolic studies, one after having remained fasted and one after having eaten breakfast and lunch.

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Effect of Fasting on Hypoglycemic Counterregulation in Type 1 Diabetes

Actual Study Start Date :

Oct 10, 2019

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fasting Subjects will remain fasted prior to insulin-induced hypoglycemia.	Other: Fasting Subjects remain fasted prior to insulin-induced hypoglycemia.
Experimental: Feeding Subjects will eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.	Other: Feeding Subjects eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.

Arm

Intervention/Treatment

Experimental: Fasting

Subjects will remain fasted prior to insulin-induced hypoglycemia.

Other: Fasting

Subjects remain fasted prior to insulin-induced hypoglycemia.

Experimental: Feeding

Subjects will eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.

Other: Feeding

Subjects eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.

Outcome Measures

Primary Outcome Measures

Glucagon [During procedure, up to 2.5 hours]
From plasma
Hepatic glucose production [During procedure, up to 2.5 hours]
From plasma
Glucose infusion rate [During procedure, up to 2.5 hours]
Amount of glucose required to maintain glycemia at ~55 mg/dL.

Secondary Outcome Measures

Epinephrine [During procedure, up to 2.5 hours]
From plasma
Peripheral glucose uptake [During procedure, up to 2.5 hours]
From plasma

Other Outcome Measures

Cortisol [During procedure, up to 2.5 hours]
From plasma
Growth Hormone [During procedure, up to 2.5 hours]
From plasma

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

males and females of any race or ethnicity
non-obese (BMI < or = to 30)
have a diagnosis of type 1 diabetes
C-peptide negative

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 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.