Gene Expression in Obesity and Insulin Resistance (Genobin)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00621205
Recruitment Status : Completed
First Posted : February 22, 2008
Last Update Posted : April 17, 2012
University of Eastern Finland
Wageningen University
Information provided by (Responsible Party):
Marjukka Kolehmainen, University of Eastern Finland

Brief Summary:
Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term 30 moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome. Thus, randomized controlled and individualized weight reduction and physical exercise intervention was conducted. In the WR group, glucose metabolism improved that was not seen in other groups. Moreover, an inverse correlation between the change in SI and the change in body weight was found (r =-0.44, p=0.026). Down-regulation of gene expression (p<0.01) involving gene ontology groups of extracellular matrix, cell death was seen. Such changes did not occur in the other groups.

Condition or disease Intervention/treatment Phase
Insulin Resistance Metabolic Syndrome Behavioral: Weight reduction, Resistance training, Aerobic exercise training, Control Not Applicable

Detailed Description:

The objective of the study is to examine the expression of genes and gene regions involved in obesity, insulin resistance and lipid metabolism. We aim to identify new genes which are involved in the development of metabolic aberrations characteristic of metabolic syndrome/type 2 diabetes. Obesity and type 2 diabetes are increasing medical and public health problems globally. Low HDL cholesterol and elevated triglyceride concentrations, and altered cholesterol metabolism are common in these states. More knowledge is urgently needed of the role of genetics in obesity, insulin resistance and abnormal lipid metabolism and their mutual relationship. This would enable the early detection of subjects at increased risk of developing obesity and the common abnormalities related to it, i.e. insulin resistance and abnormal lipid metabolism, as well as identification of subjects with genotypes associated with increased risk for above mentioned metabolic states and atherosclerotic vascular diseases and decreased responsiveness to conventional treatment. Because both weight loss and regular physical exercise result in substantial changes in glucose, insulin and lipid metabolism, studies aiming to explore the function of relevant genes are highly interesting. In this study, gene expression will be measured in adipose tissue and leucocytes before and after weight loss or period of regular physical exercise.

Originally, the Genobin study included 75 middle-aged (mean age 60±7 years) overweight or obese (mean BMI 32.9±2.8 kg/m2) men and women with impaired fasting glucose (fasting plasma glucose concentration 5.6-7.0 mmol/l) or impaired glucose tolerance (2-hour plasma glucose concentration 7.8-11.0 mmol/l and fasting plasma glucose <7.1 mmol/l) and two additional features of metabolic syndrome according to the Adult Treatment Panel III criteria [49] (for details see [50]). Subjects were randomized to one of the following groups: weight reduction (WR) (n=28), aerobic exercise training (n=15), resistance exercise training (n=14) or control group (n=18). Subjects were matched for age, sex and the status of glucose metabolism. In addition, 11 normal-weight subjects (mean age 48±9 years, mean BMI 23.7±1.9 kg/m2) were recruited. The intervention was performed in accordance with the standards of the Helsinki Declaration. The Ethics Committee of the District Hospital Region of Northern Savo and Kuopio University Hospital approved the study plan, and all participants gave written informed consent.

At the beginning of the study and after 9-11 months the following measurements were performed: plasma/serum concentrations of glucose, insulin, total and lipoprotein lipids, free fatty acids, non-cholesterol sterols, glycerol, leptin, adiponectin, ghrelin, tumor necrosis factor α, and C-reactive protein, waist and hip circumferences, body composition and resting energy expenditure. A DNA sample were drawn and an adipose tissue biopsy was performed. A frequently sampled intravenous glucose tolerance test (FSIGT) was performed to assess insulin sensitivity and secretion. Given biochemical measurements were performed also at 3 months.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Gene Expression in Adipose Tissue of Genes Involved in Obesity, Insulin Resistance and Lipid Metabolism Before and After Weight Loss or an Intensive Exercise Period
Study Start Date : October 2003
Actual Primary Completion Date : December 2004
Actual Study Completion Date : December 2005

Intervention Details:
    Behavioral: Weight reduction, Resistance training, Aerobic exercise training, Control
    Weight reduction: 12 weeks intensive weight loss, 20 weeks maintenance Resistance and aerobic exercise training: individualized and progressive training programs

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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • The subjects had impaired fasting glycemia (fasting plasma glucose concentration 5.6-7.0 mmol/L) or impaired glucose tolerance (2-hour plasma glucose concentration 7.8-11.0 mmol/L)
  • AND at least 2 other features of the metabolic syndrome according to the Adult Treatment Panel III criteria as modified by the AHA:
  • waist circumference >102 cm (males)/ >88 cm (females)
  • fasting serum triacylglycerol concentration >1.7 mmol/L
  • fasting serum HDL-cholesterol <1.0 mmol/L (males) / <1.3 mmol/L (females)
  • blood pressure >130/80 mmHg.

Exclusion Criteria:

  • liver, kidney and thyroid dysfunction

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00621205

University of Kuopio, School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre
Kuopio, Finland, FI-70211
Sponsors and Collaborators
Marjukka Kolehmainen
University of Eastern Finland
Wageningen University
Principal Investigator: Helena Gylling, Professor Unievrsity of Kuopio
Study Director: Matti IJ Uusitupa, Professor University of Eastern Finland

Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Marjukka Kolehmainen, Senior scientist, University of Eastern Finland Identifier: NCT00621205     History of Changes
Other Study ID Numbers: 152/2002
Finnish Academy 210449
First Posted: February 22, 2008    Key Record Dates
Last Update Posted: April 17, 2012
Last Verified: April 2012

Keywords provided by Marjukka Kolehmainen, University of Eastern Finland:
Insulin resistance, weight reduction, adipose tissue, peripheral
mononuclear cells, gene expression profile, transcriptomics

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Hypoglycemic Agents
Physiological Effects of Drugs