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

University Health Network, Toronto

Status and phase: Completed; Phase 2

Conditions: Healthy

Treatments: Biological: glucose or normal saline

Study type: Interventional

Funder types: Other

Identifiers

NCT02607839

12-5569-B

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Men and women, aged 18 to 60 years
2. Body mass index 20 kg/m2 to 27 kg/m2
3. Hemoglobin above 130g/L
4. Normal glucose tolerance in response to a 75g, 2-hr OGTT

Exclusion criteria

1. Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.
2. Any subject with active bleeding, bleeding diathesis, clotting abnormalities or recent surgery (within past 1 month)
3. 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).
4. History of diabetes or OGTT indicative of diabetes or impaired glucose tolerance.
5. 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.
6. Any laboratory values: AST > 2x ULN; ALT > 2x ULN TSH > 6 mU/l
7. Current addiction to alcohol or substances of abuse as determined by the investigator.
8. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
9. Taking any prescription or non-prescription medications at the time of the study
10. Having donated blood three months prior to and three months post study procedures
11. 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.
12. Known allergy, hypersensitivity or contraindication to receiving study medications.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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10 participants in 2 patient groups, including a placebo group

normal saline

Placebo Comparator group

Description:

normal saline intravenous infusion

Treatment:

Biological: glucose or normal saline

glucose

Active Comparator group

Description:

glucose intravenous infusion

Treatment:

Biological: glucose or normal saline