Effect of Postprandial Hyperinsulinaemic Hypoglycaemia on Driving Performance.

Study Overview
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Brief Summary
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The primary objective of this study is to assess the effect of the natural course of postprandial hypoglycemia vs. a postprandial euglycaemic condition on driving performance in individuals with confirmed postprandial hyperinsulinaemic hypoglycaemia after gastric-bypass surgery.

Detailed Description
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Despite the increasing prevalence of postprandial hyperinsulinaemic hypoglycaemia (PHH), clinical implications are still unclear. Anecdotal evidence from patients with PHH suggest 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 3.4mmol/l) in diabetic and non-diabetic significantly impairs cognitive-motor functioning. Of note, some of the cognitive aspects remain impaired for up to 75min, even when the hypoglycaemia is corrected. In addition to the hypoglycaemic blood glucose levels per se, the dynamics of the hypoglycaemia occurrence appears to play a role. It was shown in individuals with type 1 diabetes, that cognitive functions are affected more during a fast-fall than slow fall hypoglycaemia in the postprandial state. Driving is a frequent daily activity which integrates various mental function including visual and auditory processing, motor skills, reasoning and problem solving. Due to the potentially dangerous consequences, avoidance of hypoglycaemia-induced driving mishaps is of uttermost importance. Several studies have evaluated the impact of induced, controlled hypoglycaemia in individuals with type 1 diabetes on driving performance using driving simulators but data in PHH patients are currently lacking. Assessing the potential impact of the natural course of postprandial hypoglycaemia on driving performance in PHH patients will contribute to a better understanding of the consequences and relevance of this problem. The investigator will test the hypothesis whether driving performance during the postprandial glucose dynamics is impaired in patients with confirmed PHH.

Official Title
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Deciphering the Enigma of Postprandial Hyperinsulinaemic Hypoglycaemia After Bariatric Surgery, Part 1 C: Effect of Postprandial Hypoglycaemia on Driving Performance.

Conditions
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Roux-en-Y Gastric Bypass, Postprandial Hypoglycemia, Driving Impaired

Intervention / Treatment
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* Diagnostic Test: Oral glucose tolerance test
* Diagnostic Test: Ingestion of placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 years Roux-en-Y gastric bypass ≥1 year ago PHH defined as postprandial plasma or sensor glucose<3.0mmol/l according to the International Hypoglycaemia Study Group (1) and exclusion of other causes of hypoglycaemia Possession of a valid Swiss driver's license. Passed driver's examination at least 3 years before study inclusion. Active driving in the last 6 months before the study. Exclusion Criteria: Clinically relevant weight changes (≥5%) within the past 3 months Incapacity to give informant consent Historical or current diabetes based on HbA1c ≥6.5% without glucose-lowering treatment Haemoglobin level below 11 g/dl Ongoing treatment with glucose-lowering drugs, anorectic drugs, steroids or any medications known to affect gastric motility Active heart, lung, liver, gastrointestinal, renal or neurological disease Inability to follow study procedures Pregnancy or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will undergo two experiments in random order. In the experiments, driving performance will be assessed after administration of glucose (intervention arm) or aspartame (control arm).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glucose condition<br>In the experimental condition patients ingest 200ml of water containing 75g of glucose | Diagnostic Test: Oral glucose tolerance test<br>* Participant ingests 75g of glucose<br>|
| Placebo Comparator: Control condition<br>In the control condition patients ingest 200ml of water sweetened with 700mg of aspartame | Diagnostic Test: Ingestion of placebo<br>* Participant ingests 700mg of aspartame<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated difference in driving performance across driving features over the glycemic trajectory after glucose vs. aspartame intake | The pooled effect (z-score difference), which is the compound change in driving performance across driving features between the glucose and aspartame condition, will be calculated using a Bayesian hierarchical regression model | From -15 to 150 minutes after glucose/aspartame intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemic symptoms over the glycemic trajectory after glucose vs. aspartame intake | Hypoglycemic symptoms will be rated using the Edinburgh Hypoglycemia Symptom Scale (minimum score=11, maximum score=77, a higher score, means more symptoms) | From -15 to 180 minutes after glucose/aspartame intake | 
| Cognitive test performance after glucose vs. aspartame intake | Cognitive function will be assessed using the Digit Symbol Substitution Test | 135 minutes after glucose/aspartame intake |