Insulin and Insulin Pulses During Fasting

Mayo Clinic

Status: Enrolling

Conditions: PreDiabetes

Treatments: Other: Intralipid and heparin; Other: Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT06424015

24-002631

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 25 to 65 years old

Volunteers: Accepts Healthy Volunteers

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%

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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60 participants in 2 patient groups, including a placebo group

Intralipid and heparin

Active Comparator group

Description:

Between 0600 (-180 min) and 1300 (240 min) 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.

Treatment:

Other: Intralipid and heparin

Saline

Placebo Comparator group

Description:

Between 0600 (-180 min) and 1300 (240 min) saline will be infused

Treatment:

Other: Saline