Insulin ResistanceGenobinNCT00621205
Gene Expression in Obesity and Insulin Resistance
A study of Insulin Resistance and Metabolic Syndrome, run by Marjukka Kolehmainen at 1 site in Finland.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, Metabolic Syndrome
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 75 participants
- Where
- 1 siteFinland
- Study dates
- Oct 2003to Dec 2005
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- liver, kidney and thyroid dysfunction
Trial locations and contacts
1 site in 1 country.
Finland1 site
University of Kuopio, School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre
Kuopio, FI-70211
About this study
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
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.
Read the 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.
- Conditions
- Insulin Resistance, Metabolic Syndrome
- Being tested
- Weight reduction, Resistance training, Aerobic exercise training, Control
- Keywords
- Insulin resistance, weight reduction, adipose tissue, peripheral, mononuclear cells, gene expression profile, transcriptomics
- Medical subject headings
- Insulin Resistance, Metabolic Syndrome, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Weight reduction, Resistance training, Aerobic exercise training, ControlBehavioural
Weight reduction: 12 weeks intensive weight loss, 20 weeks maintenance Resistance and aerobic exercise training: individualized and progressive training programs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2008 (estimated)
- Study startOct 2003
- Primary completionDec 2004
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marjukka Kolehmainen
- Sponsor type
- University, hospital or other
- Collaborators
- University of Eastern Finland, Wageningen University
- Responsible party
- Sponsor-investigator, Marjukka Kolehmainen, University of Eastern Finland
- Investigators
- Helena Gylling, Professor, Principal investigator, Unievrsity of KuopioMatti IJ Uusitupa, Professor, Study director, University of Eastern Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00621205
- Sponsor's protocol ID
- 152/2002
- Other IDs
- Finnish Academy 210449
- Acronym
- Genobin
- Status last verified
- Apr 2012
- First submitted
- 11 Feb 2008
- Last updated
- 17 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Kolehmainen M, Salopuro T, Schwab US, Kekalainen J, Kallio P, Laaksonen DE, Pulkkinen L, Lindi VI, Sivenius K, Mager U, Siitonen N, Niskanen L, Gylling H, Rauramaa R, Uusitupa M. Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study. Int J Obes (Lond). 2008 Feb;32(2):292-303. doi: 10.1038/sj.ijo.0803718. Epub 2007 Sep 11.
PubMed 17848939de Mello VD, Kolehmainen M, Schwab U, Mager U, Laaksonen DE, Pulkkinen L, Niskanen L, Gylling H, Atalay M, Rauramaa R, Uusitupa M. Effect of weight loss on cytokine messenger RNA expression in peripheral blood mononuclear cells of obese subjects with the metabolic syndrome. Metabolism. 2008 Feb;57(2):192-9. doi: 10.1016/j.metabol.2007.08.024.
PubMed 18191048Hallikainen M, Kolehmainen M, Schwab U, Laaksonen DE, Niskanen L, Rauramaa R, Pihlajamaki J, Uusitupa M, Miettinen TA, Gylling H. Serum adipokines are associated with cholesterol metabolism in the metabolic syndrome. Clin Chim Acta. 2007 Aug;383(1-2):126-32. doi: 10.1016/j.cca.2007.05.006. Epub 2007 May 18.
PubMed 17573060de Mello VD, Kolehmainen M, Pulkkinen L, Schwab U, Mager U, Laaksonen DE, Niskanen L, Gylling H, Atalay M, Rauramaa R, Uusitupa M. Downregulation of genes involved in NFkappaB activation in peripheral blood mononuclear cells after weight loss is associated with the improvement of insulin sensitivity in individuals with the metabolic syndrome: the GENOBIN study. Diabetologia. 2008 Nov;51(11):2060-7. doi: 10.1007/s00125-008-1132-7. Epub 2008 Aug 30.
PubMed 18758745Schwab U, Seppanen-Laakso T, Yetukuri L, Agren J, Kolehmainen M, Laaksonen DE, Ruskeepaa AL, Gylling H, Uusitupa M, Oresic M; GENOBIN Study Group. Triacylglycerol fatty acid composition in diet-induced weight loss in subjects with abnormal glucose metabolism--the GENOBIN study. PLoS One. 2008 Jul 9;3(7):e2630. doi: 10.1371/journal.pone.0002630.
PubMed 18612464
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00621205
- Acronym / sponsor ID
- Genobin / 152/2002
- Conditions
- Insulin Resistance, Metabolic Syndrome
- Keywords
- Insulin resistance, weight reduction, adipose tissue, peripheral, mononuclear cells, gene expression profile, transcriptomics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Marjukka KolehmainenUniversity, hospital or other
- Collaborators
- University of Eastern Finland, Wageningen University
- Study start
- Oct 2003
- Primary completion
- Dec 2004 (actual)
- Study completion
- Dec 2005 (actual)
- First posted
- 22 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (1 listed)
- liver, kidney and thyroid dysfunction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Weight reduction, Resistance training, Aerobic exercise training, ControlWeight reduction: 12 weeks intensive weight loss, 20 weeks maintenance Resistance and aerobic exercise training: individualized and progressive training programs | Behavioural | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2012.
- Results publication: PubMed 17848939Kolehmainen M, Salopuro T, Schwab US, Kekalainen J, Kallio P, Laaksonen DE, Pulkkinen L, Lindi VI, Sivenius K, Mager U, Siitonen N, Niskanen L, Gylling H, Rauramaa R, Uusitupa M. Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study. Int J Obes (Lond). 2008 Feb;32(2):292-303. doi: 10.1038/sj.ijo.0803718. Epub 2007 Sep 11.
- Results publication: PubMed 18191048de Mello VD, Kolehmainen M, Schwab U, Mager U, Laaksonen DE, Pulkkinen L, Niskanen L, Gylling H, Atalay M, Rauramaa R, Uusitupa M. Effect of weight loss on cytokine messenger RNA expression in peripheral blood mononuclear cells of obese subjects with the metabolic syndrome. Metabolism. 2008 Feb;57(2):192-9. doi: 10.1016/j.metabol.2007.08.024.
- Results publication: PubMed 17573060Hallikainen M, Kolehmainen M, Schwab U, Laaksonen DE, Niskanen L, Rauramaa R, Pihlajamaki J, Uusitupa M, Miettinen TA, Gylling H. Serum adipokines are associated with cholesterol metabolism in the metabolic syndrome. Clin Chim Acta. 2007 Aug;383(1-2):126-32. doi: 10.1016/j.cca.2007.05.006. Epub 2007 May 18.
- Derived from this study: PubMed 18758745de Mello VD, Kolehmainen M, Pulkkinen L, Schwab U, Mager U, Laaksonen DE, Niskanen L, Gylling H, Atalay M, Rauramaa R, Uusitupa M. Downregulation of genes involved in NFkappaB activation in peripheral blood mononuclear cells after weight loss is associated with the improvement of insulin sensitivity in individuals with the metabolic syndrome: the GENOBIN study. Diabetologia. 2008 Nov;51(11):2060-7. doi: 10.1007/s00125-008-1132-7. Epub 2008 Aug 30.
- Derived from this study: PubMed 18612464Schwab U, Seppanen-Laakso T, Yetukuri L, Agren J, Kolehmainen M, Laaksonen DE, Ruskeepaa AL, Gylling H, Uusitupa M, Oresic M; GENOBIN Study Group. Triacylglycerol fatty acid composition in diet-induced weight loss in subjects with abnormal glucose metabolism--the GENOBIN study. PLoS One. 2008 Jul 9;3(7):e2630. doi: 10.1371/journal.pone.0002630.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helena Gylling, Professor principal investigator
Unievrsity of Kuopio
Matti IJ Uusitupa, Professor study director
University of Eastern Finland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Insulin Resistance and Metabolic Syndrome, run by Marjukka Kolehmainen at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00621205, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2012.