Sugar Doses for Low Blood Sugar

Overseen By Jason Winnick, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Jason Winnick

Must not be taking: Steroids, Beta-blockers, Bronchodilators

Disqualifiers: Pregnancy, Smoking, Cardiovascular disease, others

Compensation: Varies

Number of Visits: 3

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically inflammation-targeting steroids and medications that affect adrenergic signaling, like beta-blockers and bronchodilators.

What data supports the effectiveness of the treatment Liver Glycogen Manipulation for low blood sugar?

Research shows that increasing liver glycogen can enhance the body's response to low blood sugar by boosting hormone levels that help raise blood sugar. This suggests that manipulating liver glycogen could be effective in managing low blood sugar. ^{1 2 3 4 5}

Is the treatment of sugar doses for low blood sugar generally safe in humans?

Research on liver glycogen manipulation in large animals showed that a 20% glucose infusion increased liver glycogen without side effects, suggesting potential safety in humans. However, higher fructose levels caused lactic acidosis (a buildup of lactic acid in the body), indicating that the type and amount of sugar used are important for safety. ^{2 4 6 7 8}

How does the sugar dose treatment for low blood sugar differ from other treatments?

The sugar dose treatment for low blood sugar is unique because it involves administering specific sugars like glucose and fructose to rapidly increase liver glycogen levels, which can help stabilize blood sugar levels. This approach is different from standard treatments that typically focus on immediate glucose intake or insulin adjustments. ^{4 9 10 11 12}

Research Team

Jason Winnick, PhD

Principal Investigator

University of Cincinnati

Eligibility Criteria

This trial is for men and women aged 21-40, of any race or ethnicity, who are not obese (BMI <28 kg/m2). It's designed to include people with and without type 1 diabetes to study how liver sugar levels affect the body's response to low blood sugar.

Inclusion Criteria

My gender or race does not limit my participation.

Non-obese (BMI <28 kg/m2)

I am between 21 and 40 years old.

Exclusion Criteria

I am currently taking steroids for inflammation.

I have heart or blood vessel disease.

I have nerve, eye, or kidney damage.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Metabolic Study

Participants undergo metabolic studies with different infusions (saline, low fructose, high fructose) to assess liver glucose uptake and glycogen deposition

2 hours per session

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the metabolic studies

4 weeks

Treatment Details

Interventions

• Liver Glycogen Manipulation

Trial Overview The study tests the effects of various interventions like Low Fructose, Saline, Glucagon, Dextrose solution, High Fructose, Somatostatin, and Insulin on liver glycogen levels and hypoglycemia responses in humans. The goal is to understand better how these factors influence each other.

Participant Groups

Group I: Controls-high fructose Active Control 5 Interventions

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

Group II: Controls-low fructose Active Control 5 Interventions

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.

Group III: Controls-saline Placebo Group 5 Interventions

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.

Who Is Running the Clinical Trial?

Jason Winnick

Lead Sponsor

Trials

1

Recruited

40+

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of intraportal glucose infusion on hepatic glycogen content and degradation, and outcome of liver transplantation. [2019]

2. Denmark pubmed.ncbi.nlm.nih.gov

Normal hepatic glycogen storage after fasting and feeding in children and adolescents with type 1 diabetes. [2006]

3. United States pubmed.ncbi.nlm.nih.gov

Hepatic glycogen can regulate hypoglycemic counterregulation via a liver-brain axis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Rapid donor liver nutritional enhancement in a large animal model. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Liver glycogen-induced enhancements in hypoglycemic counterregulation require neuroglucopenia. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

A cohort study of the incidence of serious acute liver injury in diabetic patients treated with hypoglycemic agents. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Hypoglycemia: New Definitions and Regulatory Implications. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Hypoglycemia evaluation and reporting in diabetes: Importance for the development of new therapies. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Daily amylin replacement reverses hepatic glycogen depletion in insulin-treated streptozotocin diabetic rats. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Similar dose responsiveness of hepatic glycogenolysis and gluconeogenesis to glucagon in vivo. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Effect of Repeated Glucagon Doses on Hepatic Glycogen in Type 1 Diabetes: Implications for a Bihormonal Closed-Loop System. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Effects of the amylin analogue pramlintide on hepatic glucagon responses and intermediary metabolism in Type 1 diabetic subjects. [2019]