Effects of Excess Energy Intake on Metabolic Risk

NCT00562393 | Completed

• 2 other identifiers: EXCESS427639
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Insulin sensitiviy by hyperinsulinemic clamp

  28-days

Secondary Outcomes (1)

• Fat oxidation (whole body RQ and C-14 palmitate), mitochondrial function

  28-days

Study Arms (1)

Overfeeding

EXPERIMENTAL

4 weeks of 1250 kcal added daily

Other: Nutritional

Interventions

Nutritional OTHER

Overfeeding high fat diet for 28 days

Overfeeding

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Garvan Institute of Medical Research: lead

Study Sites (1)

Garvan Institute of Medical Research

Darlinghurst, New South Wales, 2010, Australia

Location

Related Publications (8)

• 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.

  PMID: 20547978 RESULT

• 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.

  PMID: 20461357 RESULT

• 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.

  PMID: 24792219 RESULT

• 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.

  PMID: 24356603 RESULT

• 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.

  PMID: 23640727 RESULT

• 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.

  PMID: 24205333 RESULT

• 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.

  PMID: 22586466 RESULT

• 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.

  PMID: 29901727 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Leonie K Heilbronn, PhD

  Garvan Institute

  PRINCIPAL INVESTIGATOR

• Lesley M Campbell, MBBS

  Garvan Insititute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Endocrinology Department St Vincent's Hospital Sydney

Study Record Dates

• First Submitted: November 20, 2007
• First Posted: November 22, 2007
• Study Start: April 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: July 14, 2015

Record last verified: 2015-07

Locations

AU (1)