Effect of Fasting Free Fatty Acids and Fasting Glucose on 1st and 2nd Phase Insulin Secretion

NCT03998709 | Withdrawn Phase 4 FDA Drug

• 2 other identifiers: 19-003325R01DK078646
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Researchers are trying to determine how changes in fasting glucose and free fatty acids (products released from fat) affect insulin secretion.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• First phase of Insulin secretion in response to manipulation of fasting FFA and glucose

  1st phase of insulin secretion (Phi 1) - physiologic parameter

  First 120 minutes of study

• Second phase of Insulin secretion in response to manipulation of fasting FFA and glucose

  2nd phase of insulin secretion (Phi 2) - physiologic parameter

  First 120 minutes of study

Secondary Outcomes (2)

• proinsulin secretion in response to manipulation of fasting FFA and glucose

  2nd 120 minutes of the study

• proinsulin clearance in response to manipulation of fasting FFA and glucose

  2nd 120 minutes of the study

Study Arms (2)

Elevation of fasting FFA and Glucose

OTHER

People with normal fasting glucose and normal fasting FFA (normal fasting glucose / normal glucose tolerance - NFG / NGT) will be studied on 2 occasions. On one occasion they will receive saline overnight and on the other they will receive intralipid and dextrose to raise fasting glucose and fasting FFA. Subsequently (on either study day) they will undergo a hyperglycemic clamp for 2 hours. After this somatostatin will be infused acutely to inhibit endogenous insulin secretion and observe clearance of beta-cell polypeptides.

Drug: Somatostatin; Other: Dextrose; Other: Intralipid

Lowering of fasting FFA and glucose

OTHER

People with elevated fasting glucose and elevated fasting FFA (Impaired fasting glucose / impaired glucose tolerance - IFG / IGT) will be studied on 2 occasions. On one occasion they will receive saline overnight and on the other they will receive insulin to lower fasting glucose and fasting FFA. Subsequently (on either study day) they will undergo a hyperglycemic clamp for 2 hours. After this somatostatin will be infused acutely to inhibit endogenous insulin secretion and observe clearance of beta-cell polypeptides.

Drug: Somatostatin; Drug: Insulin

Interventions

Somatostatin DRUG

Somatostatin will be used to inhibit endogenous insulin secretion on either study day in both arms of the study

Also known as: pancreatic clamp

Elevation of fasting FFA and Glucose; Lowering of fasting FFA and glucose

Dextrose OTHER

intravenous glucose will be used to raise fasting glucose in people with NFG / NGT

Also known as: Elevation of glucose

Elevation of fasting FFA and Glucose

Insulin DRUG

insulin will be used to lower fasting FFA and glucose in people with IFG / IGT

Also known as: glucose clamp

Lowering of fasting FFA and glucose

Intralipid OTHER

intravenous intralipid (Fat Emulsion) will be used to raise fasting FFA in people with NFG / NGT

Also known as: Elevation of FFA

Elevation of fasting FFA and Glucose

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Weight-stable, non-diabetic subjects from Biobank participants at Mayo Clinic, Rochester

You may not qualify if:

• Age \< 25 or \> 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
• HbA1c ≥ 6.5%
• Use of glucose-lowering agents.
• For female subjects: positive pregnancy test at the time of enrollment or study
• History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
• Active systemic illness or malignancy.
• Symptomatic macrovascular or microvascular disease.
• Hormone replacement therapy \>0.625 mg premarin daily

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

Somatostatin; Glucose; Insulin; Glucose Clamp Technique; soybean oil, phospholipid emulsion

Intervention Hierarchy (Ancestors)

Pituitary Hormone Release Inhibiting Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pancreatic Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Hexoses; Monosaccharides; Sugars; Carbohydrates; Proinsulin; Insulins; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Adrian Vella, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 24, 2019
• First Posted: June 26, 2019
• Study Start: February 1, 2020
• Primary Completion: December 31, 2021
• Study Completion: July 31, 2022
• Last Updated: September 9, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)