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

Mayo Clinic

Status and phase: Withdrawn; Phase 4

Conditions: Healthy

Treatments: Other: Intralipid; Drug: Somatostatin; Other: Dextrose; Drug: Insulin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03998709

19-003325

R01DK078646 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full 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.

Sex: All

Ages: 25 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Elevation of fasting FFA and Glucose

Other group

Description:

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.

Treatment:

Other: Dextrose

Drug: Somatostatin

Other: Intralipid

Lowering of fasting FFA and glucose

Other group

Description:

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.

Treatment:

Drug: Insulin

Drug: Somatostatin