Incretin Action in Physiology and Diabetes

David D'Alessio, M.D.39 enrolled

Overview

This project is designed to advance understanding of the incretin effect in health and disease. This system of gut-islet linkage is essential for normal glucose tolerance, impaired in T2DM, and amenable to therapeutic intervention. However, there are important gaps in understanding incretin function that limit application of this system; this project will address several of these. A secondary, but critical aspect of this research is focus on inter-individual variation in the physiology of the incretin system. This is a novel direction for research in this field and is critical to advancing the concept of individualized medical care in diabetes by establishing whether there is a physiologic basis for predicting the existence of responders and non-responders to incretin therapies. Currently, we have described only Aim 1 from this grant in this protocol registration. While Aim 2 and 3 are described in the grant, Aim 1 will be conducted first and the results from this Aim and / or the publication of other results in the field may affect the approach to Aims 2 and 3.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Insulin Secretion

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * healthy adult volunteers * fasting plasma glucose value ≤ 95 mg/dL, measured at screening visit * HbA1c ≤ 5.9%, measured at screening visit Exclusion Criteria: * history of diabetes diagnosis, including gestational diabetes * presence of Type II diabetes mellitus among any first degree family members * rheumatoid arthritis * inflammatory bowel disease * unstable angina or uncompensated heart failure * pulmonary disorders including COPD and asthma * malabsorptive GI disease, such as celiac disease, or gastric bypass * significant hepatic disease * renal insufficiency (eGFR \< 60 mL/kg/min) * anemia (hematocrit \< 34%) as measured at screening visit * pregnancy * uncontrolled hypertension * consumption of daily medications that alter glucose metabolism or GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)

Outcomes

Primary Outcomes

Beta cell sensitivity

Beta-cell sensitivity for each incretin will equal the slope of the insulin secretion rate divided by the specific incretin level (GLP-1 or GIP)

Time frame: 30 minute infusion periods