Mechanisms of Post-Bariatric Hypoglycemia

STATUS

Recruiting
participants needed

60
sponsor

Joslin Diabetes Center

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Updated on 19 February 2024

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diabetes

hypoglycemia

hormone levels

glucagon

continuous glucose monitoring

acarbose

hypoglycaemic

dietary intervention

gastrointestinal surgery

tolerance test

antihyperglycemic

neuroglycopenia

sensitivity testing

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 we gradually lower glucose levels, and during a controlled period of a low glucose level (hypoglycemic clamp).

We 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.

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 we gradually lower glucose levels, and during a controlled period of a low glucose level (hypoglycemic clamp).

We 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.

Details

Condition	Hypoglycemia, Hypocalcemia
Age	18years - 70years
Treatment	Activity Monitor, Continuous Glucose Monitoring, Mixed meal tolerance test, Glucagon Sensitivity Testing, Hypoglycemic Hyperinsulinemic Clamp, analysis of fecal microbiome
Clinical Study Identifier	NCT04428866
Sponsor	Joslin Diabetes Center
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	For PBH group only: Males or females diagnosed with ongoing post-bariatric hypoglycemia with prior episodes of neuroglycopenia, unresponsive to dietary intervention (low glycemic index, controlled carbohydrate portions) and trial of acarbose therapy at the maximally tolerated dose
	For post-RYGB group without PBH: Males or females with history of RYGB and no history of symptomatic hypoglycemia
	For non-surgical controls only: Males or females with no history of upper gastrointestinal surgery and no history of hypoglycemia or diabetes
	Age 18-70 years of age, inclusive, at screening
	Willingness to provide informed consent and follow all study procedures, including attending all scheduled visits
Exclusion Criteria
	Documented hypoglycemia occurring in the fasting state (> 12 hours fast)
	Chronic kidney disease stage 4 or 5 (including end-stage renal disease)
	Hepatic disease, including serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0
	Congestive heart failure, New York Heart Association class II, III or IV
	History of myocardial infarction, unstable angina or revascularization within the past 6 months or 2 or more risk factors for coronary artery disease including diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, and active tobacco use
	History of syncope (unrelated to hypoglycemia) or diagnosed cardiac arrhythmia
	Concurrent administration of -blocker therapy
	History of a cerebrovascular accident
	Seizure disorder (other than with suspect or documented hypoglycemia)
	Active treatment with any diabetes medications except for acarbose
	Active malignancy, except basal cell or squamous cell skin cancers
	Personal or family history of pheochromocytoma or disorder with increased risk of pheochromocytoma (MEN 2, neurofibromatosis, or Von Hippel-Lindau disease)
	Known insulinoma
	Major surgical operation within 30 days prior to screening
	Hematocrit < 33% (women) or <36% (men)
	Bleeding disorder, treatment with warfarin, or platelet count <50,000
	Blood donation (1 pint of whole blood) within the past 2 months
	Active alcohol abuse or substance abuse
	Current administration of oral or parenteral corticosteroids
	Pregnancy and/ or Lactation: For women of childbearing potential: there is a requirement for a negative urine pregnancy test and for agreement to use contraception during the study and for at least 1 month after participating in the study. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an intrauterine device, the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence
	Use of an investigational drug within 30 days prior to screening
	There will be no involvement of special vulnerable populations such as
	fetuses, neonates, pregnant women, children, prisoners, institutionalized or
	incarcerated individuals, or others who may be considered vulnerable
	populations

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Mechanisms of Post-Bariatric Hypoglycemia