Mechanisms of Post-Bariatric Hypoglycemia

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.

Conditions

• Hypoglycemia

Interventions

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.

Sponsors & Collaborators

• University of Michigan

  collaborator OTHER

• Joslin Diabetes Center

  lead OTHER

Principal Investigators

• Mary Elizabeth Patti, MD · Joslin Diabetes Center

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-02-26

Primary Completion

2024-09-30

Completion

2024-09-30

Countries

• United States

Study Locations