insulin resistance sugar disease
Conditions
Interventions
Study 1
1 week highcaloric/hig fat feeding in the young group: 140% of energy needs
(calculated with the Harris-Benedict equation) with the extra 40% in the form
of 2 snacks per day amounting 50%,
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Study 1 Young men (2x12): - Male healthy volunteers, 12 Hindostani and 12 Caucasians, born in the Netherlands - Age > 18 years and 20 kg/m2 and = 1 other relative;Middle-aged men (2x12): - Male volunteers, 12 Hindostani and 12 Caucasians, born in the Netherlands - Age 40-50 years - Waist circumference > 94cm for Caucasians and > 90 cm for Hindostani - BMI > 27 and = 1 other relative;Study 2. - Male healthy volunteers, 12 Hindostani and 12 Caucasians, born in the Netherlands - Age >= 18 years and = 20 kg/m2 and = 1 other relative;Study 3: Participation to study 1 (main study)
Exclusion criteria
Exclusion criteria: - Diabetes mellitus as defined by ADA criteria {2008 39 /id} - Any significant chronic disease - Renal, hepatic or endocrine disease - Cardiovascular disease, including complaints of angina pectoris or intermittend claudicatio - Smoking - Use of medication known to influence glucose and/or FFA metabolism - Recent weight changes or attempts to loose weight (> 3 kg weight gain or loss, within the last 3 months) - Difficulties to insert an intravenous catheter - Severe claustrophobia (ventilated hood, MRI) - Contra-indications for the MRI (pacemakers, internal defibrillator, clips etc) - Recent blood donation (within the last 3 months) - 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 |
|---|---|
| Study 1 We want to study potential differences at baseline and after the intervention(i.e. difference in response to such an intervention) on the following parameters: - Body fat distribution, amount of ectopic fat storage; ie: amount of visceral versus subcutaneous fat and amount of liver muscle fat as assessed by MRI/MRS - mTOR nutrient sensing pathway in skeletal muscle: mTOR, S6K1, PRAS40, raptor - muscle and adipose tissue mitochondrial function (mRNA levels of PGC-1alpha, 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)) - Insulin sensitivity of liver and muscle (hyperinsulinemic euglycemic clamp with stable isotopes) - Insulin signalling pathway in skeletal muscle and adipose tissue as assessed by expression and activation of IRS1-associated PI3K, PKB, AS160, GLUT4 - Intramyocellular lipid content (Oil-red-O staining) - Pancreas function as assessed by a oral glucos tolerance test with frequent sampling (measurement of first and second phase insulin secretion) Study 2 (addendum) - Differences in GLP-1 response to glucose between Caucasians and Hindostani - Differences in glucose and insulin levels during prolonged OGTT between Caucasians and Hindostani AD ADDENDUM SEPTEMBER 2012 (STUDY 3): We want to study potential differences on the following parameters: - volume and activity of BAT using cold-induced 18F-FDG PET-CT scan - peripheral BAT activity, measuring mRNA expression of BAT specific genes in skeletal muscle and white adipose tissue biopsies of study 1. - Glucose and triglyceride clearance by determining glucose and triglyceride levels in a fasted and cold-induced blood sample. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Compare the amount/calculation of intramyocellulair lipids measured by 7T MRI/MRS with that of the muscle biopsy (validation) - study whether the diet intervention influences the lipid composition in skeletal muscle as measured by onderzoeken 7T MRI/MRS - correlation analyses between dietary intake/ exercise and measures of insulin sensitivity: glucsoe disposal rate, IMCL in biopsies, visceral fat | — |
Countries
Netherlands
Outcome results
None listed