Clinical trial NCT06424015: Insulin and Insulin Pulses During Fasting
Official title: Effect of Insulin and Insulin Pulses on Fasting Glucagon Secretion and on Glucose Metabolism in Subjects Without Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: PreDiabetes
Keywords: insulin secretion
glucagon secretion
endogenous glucose production
glucose disappearance
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2024-05-21
Enrollment: 60
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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%

Primary outcomes:
measure: Suppression of Endogenous glucose production (EGP) by insulin
timeFrame: 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.
measure: Insulin pulse orderliness
timeFrame: Approximate Entropy (ApEn) will be calculated from the insulin concentrations observed every 2 minutes between -45 and 0 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Adrian Vella, MD
role: PRINCIPAL_INVESTIGATOR
References: