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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE4

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-01

Study Completion Date

2022-07-31

Brief Summary

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

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Detailed Description

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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.

Conditions

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Healthy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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.

Group Type OTHER

Somatostatin

Intervention Type DRUG

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

Dextrose

Intervention Type OTHER

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

Intralipid

Intervention Type OTHER

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

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.

Group Type OTHER

Somatostatin

Intervention Type DRUG

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

Insulin

Intervention Type DRUG

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

Interventions

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Somatostatin

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

Intervention Type DRUG

Dextrose

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

Intervention Type OTHER

Insulin

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

Intervention Type DRUG

Intralipid

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

Intervention Type OTHER

Other Intervention Names

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pancreatic clamp Elevation of glucose glucose clamp Elevation of FFA

Eligibility Criteria

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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

Minimum Eligible Age

25 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes