Regulation of Intestinal and Hepatic Lipoprotein Particle Production by Blood Glucose in Humans

Study Overview
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Brief Summary
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The purpose of study is to examine whether raised blood glucose enhances lipid particle production independent of effects on gastric emptying and pancreatic/ gastrointestinal hormone production.

Detailed Description
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This study will be performed on healthy, lean, non-diabetic males and females who will participate two studies each in random order, 4 to 6 weeks apart. Study A: lipoprotein turnover with intravenous infusion of normal saline. Study B: lipoprotein turnover i.v infusion of glucose. In both studies, subjects will drink a liquid formula every hour to remain in a constant fed state and will be under conditions of pancreatic clamp (with the infusion of hormones somatostatin, insulin, glucagon, growth hormone). Subjects will be blinded with regard to the treatments.

Official Title
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Regulation of Intestinal and Hepatic Lipoprotein Particle Production by Blood Glucose in Humans

Conditions
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Healthy

Intervention / Treatment
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* Biological: glucose or normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, aged 18 to 60 years Body mass index 20 kg/m2 to 27 kg/m2 Hemoglobin above 130g/L Normal glucose tolerance in response to a 75g, 2-hr OGTT Exclusion Criteria: Subject has a history of hepatitis/hepatic disease that has been active within the previous two years. Any subject with active bleeding, bleeding diathesis, clotting abnormalities or recent surgery (within past 1 month) Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL), genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP > 100 or systolic > 180). History of diabetes or OGTT indicative of diabetes or impaired glucose tolerance. Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure. Any laboratory values: AST > 2x ULN; ALT > 2x ULN TSH > 6 mU/l Current addiction to alcohol or substances of abuse as determined by the investigator. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation Taking any prescription or non-prescription medications at the time of the study Having donated blood three months prior to and three months post study procedures A pregnancy test will be performed 1 to 3 days prior to each study in all female subjects. Those who test positive for pregnancy will be excluded. Known allergy, hypersensitivity or contraindication to receiving study medications.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: normal saline<br>normal saline intravenous infusion | Biological: glucose or normal saline<br>* 20% glucose solution or normal saline, intravenous infusion<br>|
| Active Comparator: glucose<br>glucose intravenous infusion | Biological: glucose or normal saline<br>* 20% glucose solution or normal saline, intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Production of TRL-apoB48 between treatments |  | 10 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Production of TRL-apoB100 between treatments |  | 10 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lipid handling by the gut and liver