Clinical trial NCT00562393: Effects of Excess Energy Intake on Metabolic Risk
Official title: Effects of Excess Energy Intake on Metabolic Risk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Resistance
Lead sponsor: Garvan Institute of Medical Research
Sponsor class: OTHER
First posted: 2007-11-22
Enrollment: 41
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The prevalence of obesity has reached epidemic proportions and is associated with the development of insulin resistance and type 2 diabetes (T2DM). A unifying theme has emerged over the past few years suggesting that lipid oversupply to metabolic organs responsible for glucose regulation leads to insulin resistance. Fitting with this, we and others have shown that increased lipid accumulation within skeletal muscle and/or liver is associated with impaired glucose uptake. However, the underlying mechanisms that mediate changes in muscle lipid metabolism are not yet known. The overall aim of this project is to examine metabolic effects of experimental weight gain in lean and overweight individuals with and without a genetic predisposition to type 2 diabetes. We hypothesise that lean subjects will increase fatty acid oxidation and upregulate mitochondrial oxidative capacity in muscle following overfeeding to protect against body weight gain and insulin resistance, but overweight subjects with a genetic predisposition to T2DM will have a defect in this ability.


Eligibility criteria: Inclusion Criteria:

* Sedentary (\<60 min formal exercise per week)
* Aged 20-65 years

Exclusion Criteria:

* Personal history of diabetes, cardiovascular disease or hypertension
* Recent weight change (larger than 4kg in the past 3 months)
* Smoking
* Regular use of medications, except oral contraceptives
* Individuals with alcoholism or other substance abuse
* Pregnancy or lactation, women who are planning to become pregnant or who are not using adequate measures of birth control.

Primary outcomes:
measure: Insulin sensitiviy by hyperinsulinemic clamp
timeFrame: 28-days
Secondary outcomes:
measure: Fat oxidation (whole body RQ and C-14 palmitate), mitochondrial function
timeFrame: 28-days
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: Garvan Institute of Medical Research
state: New South Wales
Study officials:
affiliation: Garvan Institute
name: Leonie K Heilbronn, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Garvan Insititute
name: Lesley M Campbell, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tam CS, Viardot A, Clement K, Tordjman J, Tonks K, Greenfield JR, Campbell LV, Samocha-Bonet D, Heilbronn LK. Short-term overfeeding may induce peripheral insulin resistance without altering subcutaneous adipose tissue macrophages in humans. Diabetes. 2010 Sep;59(9):2164-70. doi: 10.2337/db10-0162. Epub 2010 Jun 14.
citation: Samocha-Bonet D, Campbell LV, Viardot A, Freund J, Tam CS, Greenfield JR, Heilbronn LK. A family history of type 2 diabetes increases risk factors associated with overfeeding. Diabetologia. 2010 Aug;53(8):1700-8. doi: 10.1007/s00125-010-1768-y. Epub 2010 May 12.
citation: Sato K, Samocha-Bonet D, Handelsman DJ, Fujita S, Wittert GA, Heilbronn LK. Serum sex steroids and steroidogenesis-related enzyme expression in skeletal muscle during experimental weight gain in men. Diabetes Metab. 2014 Dec;40(6):439-44. doi: 10.1016/j.diabet.2014.03.006. Epub 2014 Apr 30.
citation: Samocha-Bonet D, Tam CS, Campbell LV, Heilbronn LK. Raised circulating fetuin-a after 28-day overfeeding in healthy humans. Diabetes Care. 2014;37(1):e15-6. doi: 10.2337/dc13-1728. No abstract available.
citation: Heilbronn LK, Coster AC, Campbell LV, Greenfield JR, Lange K, Christopher MJ, Meikle PJ, Samocha-Bonet D. The effect of short-term overfeeding on serum lipids in healthy humans. Obesity (Silver Spring). 2013 Dec;21(12):E649-59. doi: 10.1002/oby.20508. Epub 2013 Jul 29.
citation: Heilbronn LK, Campbell LV, Xu A, Samocha-Bonet D. Metabolically protective cytokines adiponectin and fibroblast growth factor-21 are increased by acute overfeeding in healthy humans. PLoS One. 2013 Oct 18;8(10):e78864. doi: 10.1371/journal.pone.0078864. eCollection 2013.
citation: Samocha-Bonet D, Campbell LV, Mori TA, Croft KD, Greenfield JR, Turner N, Heilbronn LK. Overfeeding reduces insulin sensitivity and increases oxidative stress, without altering markers of mitochondrial content and function in humans. PLoS One. 2012;7(5):e36320. doi: 10.1371/journal.pone.0036320. Epub 2012 May 7.
citation: Elshorbagy AK, Samocha-Bonet D, Jerneren F, Turner C, Refsum H, Heilbronn LK. Food Overconsumption in Healthy Adults Triggers Early and Sustained Increases in Serum Branched-Chain Amino Acids and Changes in Cysteine Linked to Fat Gain. J Nutr. 2018 Jul 1;148(7):1073-1080. doi: 10.1093/jn/nxy062.