Insulin and Insulin Pulses During Fasting

PreDiabetes Clinical Trial

Official title:

Effect of Insulin and Insulin Pulses on Fasting Glucagon Secretion and on Glucose Metabolism in Subjects Without Type 2 Diabetes

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06424015
• Other study ID #: 24-002631
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2024
• Est. completion date: September 1, 2027

Study information

• Verified date: May 2024
• Source: Mayo Clinic
• Contact: Kim Osmundson, CCRP
• Phone: 507-255-0907
• Email: Osmundson.Kimberly[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in prediabetes.

Description:

Decreased insulin action increases glucagon concentrations. In rodents, insulin signaling restrains glucagon secretion. It is unclear if this is the case in all (subtypes of) prediabetes. Impaired hepatic insulin action exacerbates glucagon's effects on endogenous glucose production. Also, insulin resistance in the β-cell impairs negative feedback inhibition of insulin secretion. This leads to hyperinsulinemia in rodents and humans. How these variables interact is unknown. This experiment will determine how insulin variably regulates fasting glucagon (and insulin) secretion directly, or indirectly, in prediabetes.

The inability of the proinsulin to insulin ratio to reliably predict β-cell integrity, endoplasmic reticulum stress and β-cell function has led to the identification of novel markers of β-cell health. In addition, the relationship of glucagon and insulin pulses will be quantified. Preliminary data shows that there is heterogeneity in these relationships even in normal fasting glucose. Th experiment will also determine how islet hormone / glucose crosstalk and pulse characteristics contribute to prediabetes.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: September 1, 2027
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

Inclusion Criteria:

• people with normal or impaired fasting glucose and normal or impaired glucose tolerance

Exclusion Criteria:

1. HbA1c > 6.5%

2. BMI = 35 Kg/M2

3. Use of any glucose-lowering agents including metformin or sulfonylureas.

4. For female subjects: positive pregnancy test at the time of enrollment or study

5. History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.

6. Active systemic illness or malignancy.

7. Symptomatic macrovascular or microvascular disease.

8. Hematocrit < 35%

Related Conditions & MeSH terms

• PreDiabetes
• Prediabetic State

Intervention

Other:
• Intralipid and heparin
Intralipid (20%, 0.011ml/kg/min; Baxter, Healthcare, Deerfield, IL) and heparin (200 units prime, 0.2 unit/kg/min continuous) will be infused to induce acute insulin resistance
• Saline
Saline will be infused

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Suppression of Endogenous glucose production (EGP) by insulin	comparison of EGP in people with IFG vs NFG in response to insulin infusion	The rate of EGP at 240 minutes (end of study) expressed as a percentage of fasting EGP (at the start of the study i.e.: 0 minutes.
Primary	Insulin pulse orderliness	comparison of Insulin pulse orderliness measured by approximate entropy in people with IFG vs NFG	Approximate Entropy (ApEn) will be calculated from the insulin concentrations observed every 2 minutes between -45 and 0 minutes