NCT04428866

Mechanisms of Post-Bariatric Hypoglycemia

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 105 (actual)
• Sponsor: Joslin Diabetes Center · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

Post-bariatric hypoglycemia (PBH) is an increasingly recognized syndrome that is incompletely understood. The purpose of this study is to increase our level of understanding by investigating mechanisms contributing to this condition. Participation in this study will take place over four visits, which will include the following: * Wearing of a continuous glucose monitoring device; * Providing a stool sample (collected at home); * Measuring glucose and hormone levels in response to a meal; * Measuring glucose and hormone levels in response to an injection of glucagon; * Measuring hormone levels while glucose levels are gradually lowered, and during a controlled period of a low glucose level (hypoglycemic clamp). Investigators will test the hypothesis that counterregulatory hormone responses are impaired in individuals with PBH, and that differences in the intestinal bacteria (microbiome) may contribute to this condition.

Detailed description

Bariatric surgery is increasingly recognized as a potent tool for the treatment of type 2 diabetes (T2D), yielding not only weight loss but also rapid improvements in glycemia allowing discontinuation of diabetes-related medication within days after surgery. However, along with this metabolic success comes an increased incidence of severe hypoglycemia (termed post-bariatric hypoglycemia; PBH) for a subset of individuals. The goal of these studies is to identify physiological and molecular mechanisms that underlie PBH, to determine whether these changes also contribute to surgery-induced improvements in glucose regulation (homeostasis), and to define potential new therapeutic interventions for PBH. Participation in this study will take place over four visits, which will include the following: * Detailed history, physical exam, and laboratory testing to determine study eligibility * Assessment of glucose patterns using a masked continuous glucose monitor; * Analysis of a stool sample (collected at home); * Measuring glucose and hormone levels in response to a meal; * Measuring glucose and hormone levels in response to an injection of glucagon; * Measuring hormone levels while glucose levels are gradually lowered, and during a controlled period of a low glucose level (hypoglycemic clamp). Investigators will test the hypothesis that counterregulatory hormone responses are impaired in individuals with PBH, and that differences in the intestinal bacteria (microbiome) and hormones produced in response to a meal may contribute to this condition.

Conditions

• Hypoglycemia

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Continuous Glucose Monitoring	A CGM sensor (Dexcom G4 or other professional version available at onset of study) will be placed during visit 1 in blinded (masked) mode, and will be worn for 10 days. Data will be analyzed to determine patterns of glucose during both day and night intervals.
DIAGNOSTIC_TEST	activity monitor	The activity monitor (Fitbit Charge 2) will be worn by participants for 10 days to assess activity, concurrent with CGM sensor wear.
DIAGNOSTIC_TEST	Mixed meal tolerance test	After an overnight fast, participants will be given a standard liquid mixed meal; blood samples will be collected at baseline (fasting) and at defined time points after a meal for metabolic and hormonal analyses.
DIAGNOSTIC_TEST	Glucagon Sensitivity Testing	After baseline blood sampling, glucagon will be administered by injection, and blood samples will be collected for analysis of glucose and hormone responses. This will allow us to assess whether sensitivity to glucagon is altered in PBH.
DIAGNOSTIC_TEST	Hypoglycemic Hyperinsulinemic Clamp	This test will assess hormonal responses to hypoglycemia. Participants will arrive after an overnight fast. After baseline blood sampling, an infusion of insulin and glucose will be started, and infusions will be adjusted to allow glucose levels to drop very gradually. Blood samples will be collected for measurement of hormonal responses to lowering of glucose. This test will allow us to determine whether secretion of hormones which counteract hypoglycemia (counterregulatory hormones) is reduced in patients with PBH as compared with other groups.
DIAGNOSTIC_TEST	analysis of fecal microbiome	Participants will be asked to provide a fecal sample, collected at home, which will be analyzed to determine the types of bacteria present in the feces.

Timeline

• Start date: 2020-02-26
• Primary completion: 2024-09-01
• Completion: 2024-09-01
• First posted: 2020-06-11
• Last updated: 2024-01-05

Locations

1 site across 1 country: United States