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

Mayo Clinic

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Conditions

Healthy

Interventions

SomatostatinDRUG

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

DextroseOTHER

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

InsulinDRUG

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

Eligibility

Sex: ALLMin age: 25 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

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

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

Time frame: 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

Time frame: First 120 minutes of study

Secondary Outcomes

proinsulin secretion in response to manipulation of fasting FFA and glucose

proinsulin secretion - physiologic parameter

Time frame: 2nd 120 minutes of the study

proinsulin clearance in response to manipulation of fasting FFA and glucose

proinsulin clearance - physiologic parameter

Time frame: 2nd 120 minutes of the study

Data from ClinicalTrials.gov

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