In this study, the investigators will determine (a) whether metabolism (secretion and turnover) of glucagon is altered in patients with PBH, (b) whether this is affected by a meal, (c) whether PBH affects the ability of the body to produce glucose (endogenous glucose production), and (d) whether PBH affects the amount of glycogen in the liver (storage form of glucose) when fasting and after a meal. The investigators will determine the effect of glucagon to raise glucose levels after a meal. To answer these questions, participants will receive an infusion of a stable (nonradioactive) isotope of glucose and glucagon, and a meal containing a stable isotope of glucose. Glycogen will be measured by magnetic resonance imaging (MRI) of the liver before and after the meal. This information will be used to develop computer models for the glucagon pump system.
The purpose of this study is to assess post-prandial carbohydrate, hormone, and hepatic glycogen metabolism comparing individuals with post-bariatric surgery hypoglycemia (PBH+) to individuals post-bariatric surgery without hypoglycemia (PBH-). There will be 3 visits to the study center in total. In this study, the investigators will determine (a) whether metabolism (secretion and turnover) of glucagon is altered in patients with PBH, (b) whether this is affected by a meal, (c) whether PBH affects the ability of the body to produce glucose (endogenous glucose production), and (d) whether PBH affects the amount of glycogen in the liver (storage form of glucose) when fasting and after a meal. The investigators will determine the effect of glucagon to raise glucose levels after a meal. To answer these questions, participants will receive an infusion of a stable (nonradioactive) isotope of glucose and glucagon, and a meal containing a stable isotope of glucose. Glycogen will be measured by magnetic resonance imaging (MRI) of the liver before and after the meal. This information will be used to develop computer models for the glucagon pump system. During Visit 1, the participants will undergo a medical history, physical examination, vital signs, and ECG; inclusion/exclusion criteria will be assessed. Participants will also be advised to complete food log entries and to follow a low glycemic index diet. At Visit 2, a continuous glucose monitor (CGM sensor) in masked mode will be placed on the participant. During Visit 3, participants will undergo infusions of glucose, glucagon, and their respective isotope tracers, and will consume a triple tracer mixed meal containing labeled glucose. The participants will complete C13 MRS scans to estimate liver glycogen content. Participants at Joslin Diabetes Center will not have MRS; response to an exogenous subcutaneous glucagon injection in the post-prandial state will be assessed instead. Blood samples will be processed and stored for subsequent analysis.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
40
The investigators are assessing glucagon metabolism in individuals with and without PBH in fasting and post-prandial states.
The investigators are using a stable isotope glucose tracer to assess glucose metabolism in individuals with and without PBH in fasting and post-prandial states.
The investigators are assessing the metabolism of glucagon in individuals with and without PBH in fasting and post-prandial states.
The investigators are assessing the metabolism of glucose in individuals with and without PBH in fasting and post-prandial states.
The investigators assessing the metabolism of glucose in individuals with and without PBH in fasting and post-prandial states.
University of Alabama
Birmingham, Alabama, United States
RECRUITINGJoslin Diabetes Center
Boston, Massachusetts, United States
RECRUITINGBetween-group differences in iAUC for postprandial EGP
Between-group differences in endogenous glucose production (EGP) in the postprandial state, as quantified by iAUC for postprandial EGP. These measurements will be taken at baseline and after mixed-meal consumption, specifically at minutes 10, 20, 30, 60, 90, 120, 150, and 180.
Time frame: During Visit 2, within 10 days of the baseline visit
Between-group differences in the integrated postprandial response (iAUC) of Ra glucagon
Between-group differences in glucagon secretion (Ra glucagon) in the postprandial state during mixed meal testing, as quantified by integrated postprandial response (iAUC) of Ra glucagon. These measurements will be taken at baseline and after mixed-meal consumption, specifically at minutes 10, 20, 30, 60, 90, 120, 150, and 180.
Time frame: During Visit 2, within 10 days of the baseline visit
Between-group differences in EGP in the fasting state
Between-group differences in EGP in the fasting state, as quantified by fasting EGP. Samples will be collected at baseline before consumption of a mixed meal. This will be measured at baseline.
Time frame: During Visit 2, within 10 days of the baseline visit
Between-group differences in iAUC for glucose levels for 60 minutes after postprandial glucagon administration
Between-group differences in glycemic response to exogenous glucagon administration in the postprandial state, following mixed meal testing, as quantified by iAUC glucose for 60 minutes after postprandial glucagon administration. This will be measured at the end of mixed meal testing (180 minutes) and then every 10 minutes for up to 60 minutes.
Time frame: During Visit 2, within 10 days of the baseline visit
Between-group differences in insulin sensitivity, as estimated by postprandial SI derived from oral glucose minimal model
Between-group differences in insulin sensitivity, as estimated by postprandial SI derived from oral glucose minimal model. This will be measured after mixed-meal consumption (timepoints 0 minutes).
Time frame: During Visit 2, within 10 days of the baseline visit
Between-group differences in insulin secretion, as estimated by postprandial phi total
Between-group differences in insulin secretion, as estimated by postprandial phi total, derived from oral glucose minimal model. This will be measured after mixed-meal consumption (timepoint 0 minutes).
Time frame: During Visit 2, within 10 days of the baseline visit
Between-group differences in disposition index derived from oral glucose minimal model
Between group differences in disposition index, as estimated by postprandial DI, derived from oral glucose minimal model. This will be measured after mixed-meal consumption (timepoint 0 minutes).
Time frame: During Visit 2, within 10 days of the baseline visit
Between-group differences in basal glycogen content, measured by MRI
Glycogen content will be measured using magnetic resonance imaging (MRI). Spectroscopy will be performed using a 3-Tesla whole-body MR imager/spectrometer. Absolute glycogen concentrations will be calculated from the integrated area of the C1-glycogen signal at 100.1 parts per million referenced to a glycogen phantom, corrected for receiver gain and reception sensitivity. This measurement by MRI will only occur at the University of Alabama at Birmingham.
Time frame: During Visit 2, within 10 days of the baseline visit.
Between-group differences in meal-stimulated changes in glycogen content, measured by change from baseline
Glycogen content will be measured using magnetic resonance imaging (MRI). Spectroscopy will be performed using a 3-Tesla whole-body MR imager/spectrometer. Absolute glycogen concentrations will be calculated from the integrated area of the C1-glycogen signal at 100.1 parts per million referenced to a glycogen phantom, corrected for receiver gain and reception sensitivity. This measurement by MRI will only occur at the University of Alabama at Birmingham.
Time frame: During Visit 2, within 10 days of the baseline visit
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