Effect of Fasting Free Fatty Acids and Fasting Glucose on 1st and 2nd Phase Insulin Secretion
Study Details
Study Description
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 |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: 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 Names:
Other: Dextrose
intravenous glucose will be used to raise fasting glucose in people with NFG / NGT
Other Names:
Other: Intralipid
intravenous intralipid (Fat Emulsion) will be used to raise fasting FFA in people with NFG / NGT
Other Names:
|
| Other: 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 Names:
Drug: Insulin
insulin will be used to lower fasting FFA and glucose in people with IFG / IGT
Other Names:
|
Outcome Measures
Primary Outcome Measures
- First phase of Insulin secretion in response to manipulation of fasting FFA and glucose [First 120 minutes of study]
1st phase of insulin secretion (Phi 1) - physiologic parameter
- Second phase of Insulin secretion in response to manipulation of fasting FFA and glucose [First 120 minutes of study]
2nd phase of insulin secretion (Phi 2) - physiologic parameter
Secondary Outcome Measures
- proinsulin secretion in response to manipulation of fasting FFA and glucose [2nd 120 minutes of the study]
proinsulin secretion - physiologic parameter
- proinsulin clearance in response to manipulation of fasting FFA and glucose [2nd 120 minutes of the study]
proinsulin clearance - physiologic parameter
Eligibility Criteria
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).
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HbA1c ≥ 6.5%
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Use of glucose-lowering agents.
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For female subjects: positive pregnancy test at the time of enrollment or study
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History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
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Active systemic illness or malignancy.
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Symptomatic macrovascular or microvascular disease.
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Hormone replacement therapy >0.625 mg premarin daily
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- Mayo Clinic
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
- Principal Investigator: Adrian Vella, MD, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 19-003325
- R01DK078646