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In humans, insulin is secreted in pulses from the pancreatic beta-cells, and these oscillations help to maintain fasting plasma glucose levels within a narrow normal range. Given the fluctuations in insulin concentrations, oscillations enhance precision of control. The hyperinsulinemic euglycemic clamp test (clamp) involves a continuous infusion of insulin and is the gold standard for measuring insulin sensitivity. In this study, insulin sensitivity measured using the standard clamp will be compared with a clamp in which the same total amount of insulin as the standard clamp is infused every five minutes instead of continuously.
Participants with obesity and insulin resistance completing a randomized, controlled, two-arm parallel trial (Motivate) will be enrolled in this cross-sectional study. Twelve participants from the Motivate study will return within two weeks to complete two clamp tests within a week of each other. At these clamps, the insulin will be infused continuously at a dose of 40mU/m2/min during the first clamp test and the same total amount of insulin will be infused every five minutes at the second clamp. The day following the clamps, participants will return to the clinic in a fasted state and blood will be drawn for measurement of glucose and insulin.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Continuous insulin at 40mU/m2/min | Active Comparator | Paricipants will receive insulin infused continuously during the hyperinsulinemic euglycemic clamp test of insulin sensitivity. |
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| Pulsatile insulin at 40mU/m2/min | Experimental | Participants will receive insulin infused every five minutes during the hyperinsulinemic euglycemic clamp test of insulin sensitivity |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Continuous Insulin administration during hyperinsulinemic euglycemic clamp test | Other | Participants will receive insulin delivered continuously during the hyperinsulinemic euglycemic clamp test |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin sensitivity | Glucose infusion rate during the hyperinsulinemic euglycemic clamp test | One day |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin resistance | Homeostasis Model Assessment of Insulin Resistance | 24 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Candida J Rebello, Ph.D. | Contact | 225-763-3159 | Candida.Rebello@pbrc.edu | |
| Frank L Greenway, MD | Contact | 225-763-2578 | Frank.Greenway@pbrc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Candida Rebello, PhD | Pennington Biomedical Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pennington Biomedical Research Center | Recruiting | Baton Rouge | Louisiana | 70808 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37580916 | Background | Rebello CJ, Morales TS, Chuon K, Dong S, Lam VT, Purner D, Lewis S, Lakey J, Beyl RA, Greenway FL. Physiologic hormone administration improves HbA1C in Native Americans with type 2 diabetes: A retrospective study and review of insulin secretion and action. Obes Rev. 2023 Dec;24(12):e13625. doi: 10.1111/obr.13625. Epub 2023 Aug 14. |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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Participants receive insulin delivered continuously or every five minutes during the hyperinsulinemic euglycemic clamp test
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| Pulsatile Insulin administration during hyperinsulinemic euglycemic clamp test | Other | Participants will receive insulin delivered every five minutes during the hyperinsulinemic euglycemic clamp test |
|