PreDiabetes
Conditions
Keywords
insulin secretion, glucagon secretion, endogenous glucose production, glucose disappearance
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.
Interventions
OTHERIntralipid 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
OTHERSaline
Saline will be infused
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
Yes
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%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Suppression of Endogenous glucose production (EGP) by insulin | 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. | comparison of EGP in people with IFG vs NFG in response to insulin infusion |
| Insulin pulse orderliness | Approximate Entropy (ApEn) will be calculated from the insulin concentrations observed every 2 minutes between -45 and 0 minutes | comparison of Insulin pulse orderliness measured by approximate entropy in people with IFG vs NFG |
Countries
United States
Contacts
Primary ContactKim Osmundson, CCRP
Backup ContactJeanette Laugen
Outcome results
None listed