Human Models of Selective Insulin Resistance: Graded Insulin Suppression Test (GIST) Pilot & Feasibility Study
Columbia University
Summary
The goal of this study is to learn about how the hormone insulin controls blood sugar in a variety of people. The main question it aims to answer is about how much insulin the body actually needs to maintain a normal blood sugar level. Participants will be asked to come in for a one-day study visit in which they will undergo a "graded insulin suppression test" ("GIST"). The GIST involves intravenous (into the vein) infusions of octreotide, a medication that turns off the body's own production of insulin, as well as replacement of insulin at two different levels (low and high), with or without replacement of glucagon, and glucose (sugar). The study investigators will check blood sugar levels every few minutes during the procedure to determine the effect of the two different insulin levels. This study will evaluate the GIST in both healthy volunteers and those at higher risk for type 2 diabetes.
Description
This study aims to determine to what extent the hyperinsulinemia commonly associated with insulin resistance (IR) in those at risk for type 2 diabetes (T2D) is a primary phenomenon, rather than merely a secondary, compensatory response to IR. The hypothesis is that some people with obesity and hyperinsulinemia exhibit a primary, non-compensatory hyperinsulinemia that may foment IR and its dysmetabolic sequelae. If this were the case, lowering insulin levels should not result in a proportional rise in blood glucose as might be expected if the hyperinsulinemia truly were purely compensatory. Thi…
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Body mass index of 18-25 and 30-45 kg/m2 * Able to understand written and spoken English and/or Spanish * Fasting euinsulinemia (fasting serum insulin of 4-10 μU/mL) for reference group or hyperinsulinemia (fasting serum insulin ≥ 13 μU/mL) for hyperinsulinemic group on screening labs * Written informed consent (in English or Spanish) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations. Exclusion Criteria: * U…
Interventions
- DrugInsulin regular, 2.0-3.2 mU/m2/min (euinsulinemia)
Insulin infusion to recapitulate euinsulinemia (normal basal insulin)
- DrugInsulin regular, 32 mU/m2/min (hyperinsulinemia)
Insulin infusion to induce hyperinsulinemia for assessment of insulin sensitivity
- DrugOctreotide Acetate, 6-45 ng/kg/min
Suppression of endogenous insulin secretion
- DrugDextrose 20 % in Water
Production of steady-state plasma glucose (SSPG) reflective of insulin sensitivity at hyperinsulinemia
- DrugGlucagon, 0-0.5 ng/kg/min
Replacement of endogenous glucagon suppressed by octreotide. (Use is optional at the PI's discretion.)
Location
- Columbia University Irving Medical CenterNew York, New York