Understanding Hypoglycaemia After Bariatric Surgery (HYPOBAR1)

Exploring Beta Cell Function in Individuals With Postbariatric Postprandial

Postprandial hyperinsulinaemic hypoglycaemia is an increasingly recognized adverse side effect of bariatric surgery. Affected individuals experience low glucose levels 1-3 hours after intake of meals, accompanied by symptoms such as drowsiness, sweating, hunger and palpitations. Hypoglycaemia can be serious and have potential dangerous health impact (e.g. road accident or fall due to loss of consciousness). The pathophysiology is incompletely understood and more research is needed in search of preventive and therapeutic strategies.

Study Overview

• Status: Completed
• Conditions: Bariatric Surgery
• Intervention / Treatment: Other: Dietary Supplement: Glucose

Detailed Description

Obesity is a major global health concern that is associated with significant disability and mortality. Worldwide, the prevalence of obesity has doubled since 1980, affecting 13% of the global population. Bariatric surgery has been shown to be the most effective and durable treatment of severe obesity and leads to significant improvement of obesity-related comorbidity. However, postprandial hyperinsulinaemic hypoglycaemia (PHH) after bariatric surgery is a metabolic complication that is increasingly being recognized. Prevalence rates of up to 72% have been reported. PHH may have serious implications for affected patients, including negative effects on morbidity, mortality as well as quality of life. The pathophysiology of PPH is incompletely understood and suggests decreased adaptation of beta cell function to increased insulin sensitivity. The latter has been postulated to be largely secondary due to external factors outside the beta cells as a result of anatomical and hormonal changes after Roux-en-Y gastric bypass (RYGB). However, the intrinsic mechanistic effects of altered beta-cell function after RYGB in vivo are unknown and more exploration could lead to a better understanding of PHH pathogenesis and help identify targets for possible interventions. Previous studies performed enhanced beta cell analysis by following insulin synthesis in real-time based on stable isotope labelling of C-peptide during an oral glucose tolerance test (OGTT) in cohorts with normal and diabetic glucose tolerance. Applying the same methodological approach, albeit in a different target population (PPH after bariatric surgery), the present study seeks to explore whether or not the insulin hypersecretion can be explained by an increase in insulin synthesis, and secondly, whether potentially increased insulin synthesis can be related to other glucoregulatory hormones and measures of insulin sensitivity.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Division of Endocrinology, Diabetes and Clinical Nutrition, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Gastric bypass (RYGB) surgery performed ≥ 6 months ago
• Confirmed postprandial hypoglycaemia (continuous glucose monitoring or plasma glucose), with at least 2 episodes of Whipple's triad (symptoms, capillary of interstitial glucose ≤3.1mmol/L, symptom resolution by carbohydrate intake) ≤3 months ago
• Normal glucose control at recruitment and absence of (pre)diabetes before bariatric surgery
• Capacity to give informed consent

Exclusion Criteria:

• Fasting hypoglycaemia suggesting hyperinsulinism of different aetiology
• Use of medication that influence glucose metabolism
• Bariatric procedures other than RYGB
• Physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
• Moderate to severe chronic kidney disease
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OGTT with 13C-labelled leucine; Intake of 75g of glucose with 1g of 13C leucine pre-feeding	Other: Dietary Supplement: Glucose; Intake of 75g of glucose with 1g of 13C leucine pre-feeding

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractional synthesis rate of de novo C-peptide synthesis (%/hr)	Calculated	4.5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-peptide levels in blood	Measured	4.5 hours
Insulin levels in blood	Measured	4.5 hours
Glucagon levels in blood	Measured	4.5 hours
Incretin levels in blood	Measured	4.5 hours
Insulin sensitivity	Calculated	4.5 hours
Beta cell responsivity	Calculated	4.5 hours
Hepatic insulin extraction	Calculated	4.5 hours
C-peptide levels in urine	Measured	4.5 hours
C-peptide enrichment	calculated	4.5 hours

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Erasmus Medical Center
• Investigators: Principal Investigator: Christoph Stettler, MD, Inselspital, Bern University Hospital, University of Bern

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2018
• Primary Completion (Actual): November 2, 2018
• Study Completion (Actual): November 2, 2018

Study Registration Dates

• First Submitted: July 25, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): December 4, 2018
• Last Update Submitted That Met QC Criteria: December 3, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Insulin; Glucose; Incretins; Hypoglycaemia; Roux-en-Y gastric bypass (RYGB); Stable isotope
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia
• Other Study ID Numbers: HYPOBAR1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No