Effect of insulin sensitivity
on 24-h total and ingested fat oxidation
in non-obese subjects
Insulin resistance in obese subjects is suggested to be a possible mechanism through which these individuals could maintain body weight. This study was designed to determine whether independent of body mass, insulin resistance would increase fat oxidation. A secondary objective of the program is to determine whether the effect insulin resistance on fat oxidation would be modulated on diet composition.
PI:
Bakary J Sonko, Ph.D.
Bakary.Sonko@uchsc.edu
(303) 315-9037
Purpose or description:
Insulin resistance in obese subjects is suggested to be a possible mechanism through which these individuals could maintain body weight. This study was designed to determine whether independent of body mass, insulin resistance would increase fat oxidation. A secondary objective of the program is to determine whether the effect of insulin resistance on fat oxidation would be modulated on diet composition.
The role insulin resistance plays in the progression of obesity has been an issue of debate. Insulin resistance is proposed to be an adaptive mechanism for countering further body weight gain in obesity. This is believed to result from increased plasma FFA concentration and oxidation, a consequence of the increase in body weight. There is strong correlation between plasma FFA concentration and rate of fat oxidation. However, insulin resistance is not confined only to the obese state. About 25 % of the non-obese general population with normal glucose tolerance have similar degree of insulin resistance as individuals with impaired glucose tolerance or those with NIDDM. In light of the proposed weight stabilizing effect of insulin resistance in obesity, the question arises as to whether it has a protective effect against obesity in the non-obese.
We hypothesize that 24 h total and dietary fat oxidation will be significantly higher in non-obese insulin resistant individuals with normal glucose tolerance when compared to insulin sensitive subjects. We also hypothesis that diet composition (high or low fat diet) and energy balance status will have significant effect on fat oxidation in these individuals, with the insulin resistant subjects oxidizing more fat.
Design and Methods: The study recruits subjects in the age range 18 - 50 years and must be lean (BMI of 22 - 25 kg/m2). All subjects must be healthy, sedentary and should not be on any medication that could affect lipid or carbohydrate metabolism. Subjects must be prepared to eat the study diet and participate in a pre-chamber seven-day maintenance and overfeeding diet adaptation. All females must be non-pregnant, non-lactating and must be on a birth control pill. A total of 40 subjects will be recruited locally into the study. Subjects will be recruited through advertisements on campus and in the newspapers. Study Consent will be administered through Colorado Multi-Institutional Review Board approved guidelines
Clamp and Body composition estimation: A euglycemic clamp technique will be used to determine each subject's level of insulin sensitivity. This is a 3-hour insulin/glucose study to determine the rate of insulin mediated plasma glucose disposal. Body composition will be estimated using the dual energy x-ray absorptiometer (DEXA). DEXA uses low energy x-ray beams to determine body composition. To measure body composition, the subject will lie on a table, and the arm of the DEXA will pass over him/her. This test will take about 30 min. DEXA measurements could give information about fat mass, lean tissue, bone mass, and bone mineral content.
Dietary treatments: There will be four diet treatments. These will be high and low fat maintenance diets (Low fat diet: 60:25:15 for CHO:Fat:Prot as % energy respectively, and high Fat diet: 40:45:15 for as % energy respectively), and high and low fat overfeeding diets (these will consist of adding an extra 25 % of energy intake to the two maintenance diets). The effects of each of these diets on rates of fat oxidation in the calorimeter will be estimated for each subject. The fat in the test meals will be labeled with carbon-13 (stable isotope of carbon) to allow estimation of ingested fat oxidation. The subjects will be put on each diet for seven days to adapt, and on day 8 they will eat the same diet while inside the calorimeter. There will be at least one week of washout period between consecutive study sections. The effects of the different dietary fat treatments on plasma glucose and lipid profiles (insulin, glucose, TG, FFA, HDL, LDL and total cholesterol) will be assessed for each treatment.
Calorimetry: Twenty-four hour total and dietary fat oxidation will be determined using a whole-room indirect calorimeter in combination with stable isotope ratio mass spectrometry. Carbohydrate and protein oxidation will also be estimated. Energy expenditure will be calculated from O2 consumption and CO2 production. Fat and carbohydrate oxidation will be estimated from non-protein respiratory quotient values. Dietary fat oxidation will be estimated from breath 13C enrichment plus the subject's CO2 production while in the calorimeter.
Isotope ratio Mass spectrometry and exogenous fat oxidation: A straw and vacutainers (duplicates) (Becton Dickson Inc.) will be used to collect breath CO2 samples from the subject at 08:00 (baseline), and at 30 minute intervals from 08:00 until 10:00 PM. Further samples will be collected at 05:00, 05:30, 06:00, 06:30, and 07:00 the end of the study. A stable isotope ratio mass spectrometer will be used to determine breath 13CO2 enrichment.
Specialized facilities or techniques ([links], if any):
13C isotope ratio mass spectrometry, whole-body indirect calorimetry and euglycemic insulin clamp techniques.
Supported by (grants/foundation support/agencies, etc):
NIH RO3 DK58946
UCD CNRU Grant
UCD GCRC Grant
Staff and/or affiliated personnel:
Tracy Copp: PRA to Isotope Mass Spec.
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