Liver Glycogen and Hypoglycemia in Humans

NCT03241706 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 2016-7982
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to learn more about how sugar levels in the liver affect the ability of people both with and without type 1 diabetes. People with type 1 diabetes do not make their own insulin, and are therefore required to give themselves injections of insulin in order to keep their blood sugar under control. However, very often people with type 1 diabetes give themselves too much insulin and this causes their blood sugar to become very low, which can have a negative impact on their health. When the blood sugar becomes low, healthy people secrete hormones such as glucagon and epinephrine (i.e., adrenaline), which restore the blood sugar levels to normal by increasing liver glucose production into the blood. However, in people with type 1 diabetes, the ability to release glucagon and epinephrine is impaired and this reduces the amount of sugar the liver is able to release. People with type 1 diabetes also have unusually low stores of sugar in their livers. It has been shown in animal studies that when the amount of sugar stored in the liver is increased, it increases the release of glucagon and epinephrine during insulin-induced hypoglycemia. In turn, this increase in hormone release boosts liver sugar production. However, it is not known if increased liver sugar content can influence these responses in people with and without type 1 diabetes. In addition, when people with type 1 diabetes do experience an episode of low blood sugar, it impairs their responses to low blood sugar the next day. It is also unknown whether this reduction in low blood sugar responses is caused by low liver sugar levels. The investigators want to learn more about how liver sugar levels affect the ability to respond to low blood sugar.

Conditions

Hypoglycemia; Iatrogenic

Keywords

hypoglycemia; type 1 diabetes; liver glucose metabolism

Outcome Measures

Primary Outcomes (3)

• Epinephrine

  Hormone

  2 hours

• Glucagon

  Hormone

  2 hours

• Glucose Infusion Rate

  Whole-body responses

  2 hours

Secondary Outcomes (3)

• Liver Glycogen

  2 hours

• Hepatic Glucose Production

  2 hours

• Peripheral Glucose Uptake

  2 hours

Study Arms (3)

Controls-saline

PLACEBO COMPARATOR

Each subject from Group 1 will undergo a metabolic study where saline is infused so as to not stimulate liver glucose uptake and glycogen deposition.

Drug: Saline; Drug: Somatostatin; Drug: Insulin; Drug: Glucagon; Drug: Dextrose solution

Controls-high fructose

ACTIVE COMPARATOR

A second group of control subjects will undergo a single metabolic study using a higher dose of fructose (6.5 mg/kg/min).

Drug: Low Fructose; Drug: Somatostatin; Drug: Insulin; Drug: Glucagon; Drug: Dextrose solution

Controls-low fructose

ACTIVE COMPARATOR

Each subject from Group 1 will undergo another metabolic study where fructose (1.3 mg/kg/min) is infused so as to stimulate liver glucose uptake and glycogen deposition.

Drug: Somatostatin; Drug: Insulin; Drug: Glucagon; Drug: Dextrose solution; Drug: High Fructose

Interventions

Low Fructose DRUG

IV fructose (1.3 mg/kg/min)

Controls-high fructose

Saline DRUG

Saline given as a comparison to fructose.

Controls-saline

Somatostatin DRUG

IV infusion of somatostatin (60 ng/kg/min)

Also known as: SRIF

Controls-high fructose; Controls-low fructose; Controls-saline

Insulin DRUG

IV infusion of insulin between 20-60 mU/m2/min.

Controls-high fructose; Controls-low fructose; Controls-saline

Glucagon DRUG

IV glucagon (0.65 ng/kg/min).

Controls-high fructose; Controls-low fructose; Controls-saline

Dextrose solution DRUG

IV dextrose to clamp the plasma glucose at the desired level.

Also known as: d20

Controls-high fructose; Controls-low fructose; Controls-saline

High Fructose DRUG

IV-fructose (6.5 mg/kg/min)

Controls-low fructose

Eligibility Criteria

• Age: 21 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females of any race or ethnicity.
• Aged 21-40 years.
• Non-obese (BMI \<28 kg/m2).

You may not qualify if:

• Pregnant women.
• Cigarette smoking.
• Taking inflammation-targeting steroids (e.g., prednisone).
• Taking medications targeting adrenergic signaling (e.g., beta-blockers, bronchodilators).
• Abnormal hematocrit or electrolyte levels.
• The presence of cardiovascular or peripheral vascular disease.
• The presence of neuropathy, retinopathy or nephropathy.
• Any metal in the body that would make magnetic resonance spectroscopy dangerous.

Sponsors & Collaborators

• Jason Winnick: lead

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

MeSH Terms

Conditions

Hypoglycemia; Diabetes Mellitus, Type 1

Interventions

Sodium Chloride; Somatostatin; Insulin; Glucagon; High Fructose Corn Syrup

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Pituitary Hormone Release Inhibiting Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pancreatic Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Proinsulin; Insulins; Proglucagon; Dietary Sugars; Dietary Carbohydrates; Carbohydrates; Sugars; Nutritive Sweeteners; Sweetening Agents; Flavoring Agents; Food Additives; Food Ingredients; Specialty Uses of Chemicals; Chemical Actions and Uses; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Jason Winnick, PhD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The subjects will not be informed which treatment they will receive for a given trial.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 7, 2017
• Study Start: August 2, 2018
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)