diabetes mellitus type 2 insulin resistance insulineresistentie cardiovascular disease cardiovasculaire aandoening hart- en vaataandoening ectopic fat accumulation ectopische vetophoping mitochondrial dysfunction mitochdonriële dysfunctie
Conditions
Interventions
High-fat-high-calorie-diet (HFHC) (young group):
Consisting of a subject's normal diet plus 375 cc cream per day, providing 150% of energy demands and consisting of 50% fat. Duration of HFHC diet: 5
Sponsors
Leiden University Medical Center
Eligibility
Inclusion criteria
Inclusion criteria: We will study: 1. Young, healthy male Caucasians and Hindostani before and after 5 days of high-fat-high-calorie diet on the one hand, and; 2.Middle-aged male Caucasians and Hindostani with abdominal adiposity before and after 8 days of caloric restriction on the other hand. Young men: 1. Male healthy volunteers, 12 Hindostani and 12 Caucasians, born in the Netherlands; 2. Age >= 18 years and = 19 and = relative. Middle-aged men: 1. Male volunteers, 12 Hindostani and 12 Caucasians, born in the Netherlands; 2. Age 40 - 50 years; 3. Waist circumference > 94 cm for Caucasians and > 90 cm for Hindostani; 4. BMI >= 25 and = 1 other relative.
Exclusion criteria
Exclusion criteria: 1. Diabetes mellitus as defined by ADA criteria; 2. Any significant chronic disease; 3. Renal, hepatic or endocrine disease; 4. Clinical cardiovascular disease, including complaints of angina pectoris or intermittent claudication; 5. Smoking; 6. Use of medication known to influence glucose and/or lipid metabolism; 7. Recent weight changes or attemps to lose weight (> 3 kg weight gain or loss, within the last 3 months); 8. Difficulties to insert an intravenous catheter; 9. Severe claustrophobia; 10. Contra-indications for MRI; 11. Recent blood donation (within the last 3 months); 12. Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Difference in all of the following study endpoints between Caucasians and Hindostani at baseline and after a dietary intervention; HFHC in the young group and VLCD in the middle-aged men: 1. Whole body glucose disposal determined by [6,6-2H2] glucose infusion and a two-step hyperinsulinaemic euglycaemic clamp; 2. EGP determined by [6,6-2H2] glucose infusion and a two-step hyperinsulinaemic euglycaemic clamp; 3. Glucose and lipid oxidation as determined by indirect calorimetry; 4. Body fat distribution: Hepatic and myocardial triglyceride content, visceral/subcutaneous abdominal fat and cardiac function, assessed by MRI/MRS; 5. Insulin signalling pathway in skeletal muscle and adipose tissue as assessed by expression and activation of IRS1-associated PI3K, PKB, AS160, GLUT4; 6. mTOR nutrient sensing pathway in skeletal muscle: mTOR, S6K1, PRAS40, raptor; 7. Muscle and adipose tissue mitochondrial function (mRNA levels of PGC-1á, mitochondrial enzymes, including the complexes of the electron transport chain/oxidative phosphorylation, uncoupling protein 3 [UCP3], mitochondrial copy number, and activity of mitochondrial enzymes (citrate synthase and cytochrome C oxidase)); 8. Intramyocellular lipid content (Oil-red-O staining) and ceramide, acyl-co-enzyme A and triacylglycerol, and diacylglycerol levels; 9. Pancreatic function (first and second phase insulin response) as assessed by OGTT (only measured before the intervention); 10. Adipocyte function before the intervention: Plasma FFA’s, resistin, adiponectin, leptin, inflammatory mediators; 11. Calorie intake and daily activities as determined by a 3-day diary. | — |
Contacts
Public ContactLeontine E.H. Bakker
PO Box 9600
Outcome results
None listed