Effect of Fasting on Hypoglycemic Counterregulation in Type 1 Diabetes

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.

Study Overview

• Status: Recruiting
• Conditions: Hypoglycemia; Type1diabetes
• Intervention / Treatment: Other: Fasting; Other: Feeding

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 Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jason Winnick, PhD; Phone Number: 513-558-4437; Email: jason.winnick@uc.edu
• Study Contact Backup: Name: Alyssa Randolph; Phone Number: 513-558-3427; Email: Randolas@ucmail.uc.edu

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0547
      • Recruiting
      • University of Cincinnati
      • Contact: Jason Winnick, PhD; Phone Number: 513-558-4437; Email: jason.winnick@uc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epinephrine	From plasma	During procedure, up to 2.5 hours
Peripheral glucose uptake	From plasma	During procedure, up to 2.5 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortisol	From plasma	During procedure, up to 2.5 hours
Growth Hormone	From plasma	During procedure, up to 2.5 hours

Collaborators and Investigators

• Sponsor: University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2019
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 12, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): September 3, 2024
• Last Update Submitted That Met QC Criteria: August 29, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: glucagon; liver glycogen; hepatic glucose metabolism
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
• Other Study ID Numbers: 2019-0816

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No