Liver Glycogen and Hypoglycemia in Humans

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

Interventions

DRUG

Low Fructose

IV fructose (1.3 mg/kg/min)

DRUG

Saline

Saline given as a comparison to fructose.

DRUG

Somatostatin

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

DRUG

Insulin

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

DRUG

Glucagon

IV glucagon (0.65 ng/kg/min).

DRUG

Dextrose solution

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

DRUG

High Fructose

IV-fructose (6.5 mg/kg/min)

Sponsors & Collaborators

• Jason Winnick

  lead OTHER

Principal Investigators

• Jason Winnick, PhD · University of Cincinnati

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

21 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-08-02

Primary Completion

2028-05-31

Completion

2028-05-31

FDA Drug

Yes

Countries

• United States

Study Locations