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

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ClinicalTrials.gov Identifier: NCT03998709
Recruitment Status : Recruiting
First Posted : June 26, 2019
Last Update Posted : March 2, 2020
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Adrian Vella, Mayo Clinic

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

Condition or disease Intervention/treatment Phase
Healthy Drug: Somatostatin Other: Dextrose Drug: Insulin Other: Intralipid Phase 4

Detailed Description:
Non-invasive measurement of β-cell health is a long-hoped for tool in diabetes research. The observation that Type 2 Diabetes Mellitus (T2DM), and acute insulin resistance increase proinsulin concentrations led to the suggestion that a proinsulin/insulin ratio is a marker of β-cell integrity. However, proinsulin has a longer half-life (20-30min) than insulin (5min) and, unlike insulin, is not extracted by the liver. This limitation can only be overcome by direct and simultaneous measurement of insulin and proinsulin secretion. This experiment will measure in vivo proinsulin clearance so that proinsulin secretion can be calculated in people with differing degrees of glucose tolerance. It is also notable that subgroups of prediabetes differ in their fasting glucose and free fatty acid (FFA) concentrations. Whether short-term alteration of fasting glucose and FFA can alter subsequent prandial glucose metabolism is unknown. The loss of 1st phase insulin secretion(thought to represent release of pre-formed insulin granules) in T2DM can be partly restored by improved glycemic control although 2nd phase insulin secretion (thought to represent de novo synthesis of insulin) is unchanged. This experiment we will ascertain if changes in fasting FFA and glucose alter 1st and 2nd phase insulin secretion in people without diabetes.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effect of Fasting Free Fatty Acids and Fasting Glucose on 1st and 2nd Phase Insulin Secretion
Actual Study Start Date : February 1, 2020
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Elevation of fasting FFA and Glucose
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
Somatostatin will be used to inhibit endogenous insulin secretion on either study day in both arms of the study
Other Name: pancreatic clamp

Other: Dextrose
intravenous glucose will be used to raise fasting glucose in people with NFG / NGT
Other Name: Elevation of glucose

Other: Intralipid
intravenous intralipid (Fat Emulsion) will be used to raise fasting FFA in people with NFG / NGT
Other Name: Elevation of FFA

Lowering of fasting FFA and glucose
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
Somatostatin will be used to inhibit endogenous insulin secretion on either study day in both arms of the study
Other Name: pancreatic clamp

Drug: Insulin
insulin will be used to lower fasting FFA and glucose in people with IFG / IGT
Other Name: glucose clamp




Primary Outcome Measures :
  1. First phase of Insulin secretion in response to manipulation of fasting FFA and glucose [ Time Frame: First 120 minutes of study ]
    1st phase of insulin secretion (Phi 1) - physiologic parameter

  2. Second phase of Insulin secretion in response to manipulation of fasting FFA and glucose [ Time Frame: First 120 minutes of study ]
    2nd phase of insulin secretion (Phi 2) - physiologic parameter


Secondary Outcome Measures :
  1. proinsulin secretion in response to manipulation of fasting FFA and glucose [ Time Frame: 2nd 120 minutes of the study ]
    proinsulin secretion - physiologic parameter

  2. proinsulin clearance in response to manipulation of fasting FFA and glucose [ Time Frame: 2nd 120 minutes of the study ]
    proinsulin clearance - physiologic parameter



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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

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

Exclusion Criteria

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03998709


Contacts
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Contact: Paula Giesler, RN 507-255-8345 Giesler.Paula@mayo.edu

Locations
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United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Paula Giesler, RN    507-255-8345    Giesler.Paula@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Adrian Vella, MD Mayo Clinic
Additional Information:
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Responsible Party: Adrian Vella, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03998709    
Other Study ID Numbers: 19-003325
R01DK078646 ( U.S. NIH Grant/Contract )
First Posted: June 26, 2019    Key Record Dates
Last Update Posted: March 2, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Soybean oil, phospholipid emulsion
Somatostatin
Physiological Effects of Drugs
Fat Emulsions, Intravenous
Parenteral Nutrition Solutions
Pharmaceutical Solutions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists