Clinical trial NCT03998709: Effect of Fasting Free Fatty Acids and Fasting Glucose on 1st and 2nd Phase Insulin Secretion
Official title: Effect of Fasting Free Fatty Acids and Fasting Glucose on 1st and 2nd Phase Insulin Secretion
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Healthy
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-06-26
Enrollment: 0
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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.

Eligibility 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

Primary outcomes:
measure: First phase of Insulin secretion in response to manipulation of fasting FFA and glucose
timeFrame: First 120 minutes of study
measure: Second phase of Insulin secretion in response to manipulation of fasting FFA and glucose
timeFrame: First 120 minutes of study
Secondary outcomes:
measure: proinsulin secretion in response to manipulation of fasting FFA and glucose
timeFrame: 2nd 120 minutes of the study
measure: proinsulin clearance in response to manipulation of fasting FFA and glucose
timeFrame: 2nd 120 minutes of the study
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: