Status:
COMPLETED
Mechanism of Fatty Acid-Induced Impairment of Glucose-Stimulated Insulin Secretion
Lead Sponsor:
University Health Network, Toronto
Conditions:
Insulin Resistance Syndrome X
Pancreatic Beta Cell Function
Eligibility:
MALE
35-65 years
Phase:
PHASE4
Brief Summary
A prolonged elevation of plasma free fatty acids (FFA) impairs glucose stimulated insulin secretion. The concept of fatty acid impairment of glucose stimulated insulin secretion (lipotoxicity) has now...
Detailed Description
Free fatty acids will be elevated approximately 2-fold for 48 hours by intravenous infusion of Intralipid and heparin. 15 abdominally obese insulin resistant, but otherwise healthy, non-diabetic men w...
Eligibility Criteria
Inclusion
- The following criteria will be used for the selection of insulin resistant non-diabetic men aged 35-65 years:
- Written informed consent obtained
- Body mass index (BMI) \> 27 kg/m2
- Fasting triglycerides \> 2 mmol/l and \< 5 mmol/l
- Waist circumference \> 90 cm
- Fasting blood glucose \< 7 mmol/l
- In order to keep the number of study subjects to a minimum (n=15), in view of the cost of these labor-intensive metabolic studies, the investigators will be studying males only 35 to 65 years of age. This will allow them to study as homogeneous a group of subjects as possible. If significant protective effects of NAC on beta cell function are detected, they will study women using a similar protocol at a later stage.
- Hemoglobin above 130 g/L
Exclusion
- Patient has a history of hepatitis/hepatic disease that has been active within the previous two years
- 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) or proliferative retinopathy
- Fasting blood glucose \> 7 mmol/l or known diabetes
- Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmias or conduction delays on ECG, unstable angina, or decompensated heart failure
- Any laboratory values: AST \> 2x ULN; ALT \> 2x ULN TSH \> 6 mU/l
- Known or suspected allergy to the medication or a history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions
- Current addiction to alcohol or substances of abuse as determined by the investigator
- Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
- Any lipid lowering or hypoglycemic agents
- Previous history of asthma
- Will not donate blood three months prior to and three months post study procedures
Key Trial Info
Start Date :
January 1 2004
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
January 1 2008
Estimated Enrollment :
15 Patients enrolled
Trial Details
Trial ID
NCT00188773
Start Date
January 1 2004
End Date
January 1 2008
Last Update
June 5 2008
Active Locations (1)
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1
University Health Network
Toronto, Ontario, Canada, M5G 2C4