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Forecasting and Preventing Post-Bariatric Hypoglycaemia WP 2

Not Applicable
Completed
Conditions
Post-bariatric Hypoglycaemia
Roux-en-Y Gastric Bypass
Interventions
Other: 15 g dextrose
Other: 5 g dextrose
Other: Protein bar
Registration Number
NCT05250271
Lead Sponsor
Lia Bally
Brief Summary

The overall aim of this study is to develop a sustainable hypoglycemia correction strategy.

Detailed Description

Obesity is a major global public health concern, for which the most effective therapy is bariatric surgery. Beyond weight loss, bariatric surgery exerts powerful effects on glucose metabolism, achieving complete type 2 diabetes remission in up to 70% of cases. An exaggeration of these effects, however, can result in an increasingly recognized metabolic complication known as postprandial hyperinsulinaemic hypoglycaemia or post-bariatric hypoglycaemia (PBH). The condition manifests 1-3 years after surgery with meal-induced hypoglycaemic episodes. Emerging data suggests that PBH is more frequent than previously thought and affects approximately 30% of postoperative patients, more commonly after gastric bypass than sleeve gastrectomy. Of note, asymptomatic PBH is common, as shown in studies using continuous glucose monitoring (CGM). It is known from extensive research in people with diabetes that recurrent episodes of hypoglycaemia impair counter regulatory defences against subsequent events, predisposing patients to severe hypoglycaemia.

Despite the increasing prevalence of PBH, clinical implications in this population are still unclear. Anecdotal evidence from patients with PBH suggests a high burden for these patients due to the recurrent hypoglycaemias with possibly debilitating consequences. It is well established that even mild hypoglycaemia (plasma glucose of 3.4 mmol/L) in diabetic and non-diabetic patients impairs various cognitive domains. Of note, some of the cognitive functions remain impaired for up to 75 min, even when the hypoglycaemia is corrected. Further concerns exist from observational studies showing associations between PBH during pregnancy and poor foetal growth.

Thus, it is important to timely detect and treat hypoglycaemia with an intervention that allows quick recovery of glycaemia to a safe level, thereby alleviating symptoms and eliminating the risk of potentially hazardous sequelae. Current diabetes-inspired guidelines recommend to correct hypoglycaemia with 15-20 g fast-acting carbohydrates, preferably glucose. However, clinical experience with PBH patients shows that the rapid spikes in glycaemia following correction of hypoglycaemia with such proposed strategies may trigger rebound hypoglycaemia in PBH patients. However, hypoglycaemia correction strategies that are tailored to the specific needs of PBH do not exist currently. Previous research suggests that glucose co-ingested with amino acids induces a metabolic environment that could be favourable for PBH patients due to elevated glucagon levels. However, it currently remains speculative whether combinations of amino acids with glucose could offer more suitable and sustainable PBH correction strategies.

Given the potentially hazardous consequences of hypoglycaemia, development of hypoglycaemia management strategies to adequately predict and treat critical blood glucose levels in the PBH population are urgently needed. Such strategies have to significantly lower the burden of PBH and increase patient safety.

The overall aim or the PBH forecast project (containing 3 WPs) is to prevent hypoglycaemic events in patients with PBH and to develop a sustainable hypoglycaemia correction strategy. The primary objective of WP 2 is to test different nutritional strategies for sustainable hypoglycaemia correction (e.g. minimising time spent hypoglycaemic without causing rebound hyper- and hypoglycaemia).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
8
Inclusion Criteria
  • Post-bariatric surgery patients (Roux-en-Y gastric bypass) with PBH, defined as postprandial plasma or sensor glucose <3.0 mmol/L according to the International Hypoglycaemia Study Group and exclusion of other causes of hypoglycaemia
  • Age ≥18 years
Exclusion Criteria
  • Inability to give informed consent as documented by signature
  • Pregnant or lactating women
  • Inability or contraindications to undergo the investigated intervention
  • Drugs interfering with blood glucose (e.g. SGLT-2 inhibitors, acarbose) during the time of investigation
  • Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Treatment sequence 415 g dextroseSequence of the treatments: Glucose (5g) - Protein bar - Glucose (15g)
Treatment sequence 4Protein barSequence of the treatments: Glucose (5g) - Protein bar - Glucose (15g)
Treatment sequence 515 g dextroseSequence of the treatments: Protein bar - Glucose (15g) - Glucose (5g)
Treatment sequence 5Protein barSequence of the treatments: Protein bar - Glucose (15g) - Glucose (5g)
Treatment sequence 15 g dextroseSequence of the treatments: Glucose (15g) - Glucose (5g) -Protein bar
Treatment sequence 1Protein barSequence of the treatments: Glucose (15g) - Glucose (5g) -Protein bar
Treatment sequence 115 g dextroseSequence of the treatments: Glucose (15g) - Glucose (5g) -Protein bar
Treatment sequence 45 g dextroseSequence of the treatments: Glucose (5g) - Protein bar - Glucose (15g)
Treatment sequence 35 g dextroseSequence of the treatments: Glucose (5g) - Glucose (15g) - Protein bar
Treatment sequence 25 g dextroseSequence of the treatments: Glucose (15g) - Protein bar - Glucose (5g)
Treatment sequence 3Protein barSequence of the treatments: Glucose (5g) - Glucose (15g) - Protein bar
Treatment sequence 315 g dextroseSequence of the treatments: Glucose (5g) - Glucose (15g) - Protein bar
Treatment sequence 55 g dextroseSequence of the treatments: Protein bar - Glucose (15g) - Glucose (5g)
Treatment sequence 615 g dextroseSequence of the treatments: Protein bar - Glucose (5g) - Glucose (15g)
Treatment sequence 6Protein barSequence of the treatments: Protein bar - Glucose (5g) - Glucose (15g)
Treatment sequence 215 g dextroseSequence of the treatments: Glucose (15g) - Protein bar - Glucose (5g)
Treatment sequence 2Protein barSequence of the treatments: Glucose (15g) - Protein bar - Glucose (5g)
Treatment sequence 65 g dextroseSequence of the treatments: Protein bar - Glucose (5g) - Glucose (15g)
Primary Outcome Measures
NameTimeMethod
Time in glucose target rangeDuring 40 minutes after hypoglycaemia correction

The primary endpoint is time in glucose target range (plasma glucose 3.9-5.5 mmol/L).

Secondary Outcome Measures
NameTimeMethod
Percentage of time with plasma glucose <3.9 mmol/LDuring 40 minutes after hypoglycaemia correction

Units: %

Percentage of time with sensor glucose <3.0 mmol/LDuring 150 minutes after hypoglycaemia correction

The sensor glucose values will be adjusted to plasma glucose to increase accuracy

Percentage of time with sensor glucose >5.5 mmol/LDuring 150 minutes after hypoglycaemia correction

The sensor glucose values will be adjusted to plasma glucose to increase accuracy

Percentage of time with sensor glucose <3.9 mmol/LDuring 150 minutes after hypoglycaemia correction

The sensor glucose values will be adjusted to plasma glucose to increase accuracy

Percentage of time with plasma glucose <3.0 mmol/LDuring 40 minutes after hypoglycaemia correction

Units: %

Time to euglycaemiaUntil 40 minutes after inital hypoglycaemia correction or 180 minutes after meal intake (the later timepoint of the two)

Time to euglycaemia after hypoglycaemia correction (plasma glucose ≥3.9 mmol/L)

Percentage of time with plasma glucose >5.5 mmol/LDuring 40 minutes after hypoglycaemia correction

Units: %

Percentage of time with plasma glucose >10.0 mmol/LDuring 40 minutes after hypoglycaemia correction

Units: %

Peak plasma glucoseUntil 40 minutes after inital hypoglycaemia correction or 180 minutes after meal intake (the later timepoint of the two)

Peak plasma glucose (mmol/L)

Glucagon15 minutes after hypoglycaemia correction

Serum glucagon concentration

Percentage of time with sensor glucose >10.0 mmol/LDuring 150 minutes after hypoglycaemia correction

The sensor glucose values will be adjusted to plasma glucose to increase accuracy

Rebound hypoglycaemiaDuring 150 minutes after hypoglycaemia correction

Proportion of participants with rebound hypoglycaemia (plasma glucose \<3.0 mmol/L following successful primary hypoglycaemia correction defined as plasma glucose ≥3.9 mmol/L)

Insulin15 minutes after hypoglycaemia correction

Serum insulin concentration

Trial Locations

Locations (1)

Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism (UDEM), Inselspital, Bern University Hospital

🇨🇭

Bern, BE, Switzerland

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