Diabetes MellitusFATFUNgenesNCT04040595
The Genetics of Adipose Tissue Function and Its Link to Type 2 Diabetes and Heart Disease
A study testing Abdominal fat biopsy in people with Diabetes Mellitus, run by Royal Devon and Exeter NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Obesity is a major risk factor for Type 2 diabetes. However, two obese people of the same height and weight can have very different risks of the condition. As a greater proportion of the population is becoming obese, scientists need to understand more about why some people develop Type 2 diabetes at lower weight and… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Abdominal fat biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 207 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 7 Mar 2019to 20 May 2021
- 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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Demographics: Age 18-75 inclusive
- Ethnicity: Reflective of local demographic
- Mental capacity: Willing and able to provide informed consent
Who cannot join
- Medical history: History of bariatric surgery and recent significant weight loss/gain (+/- 3 kgs/ half a stone in the last 3 months); connective tissue disease, pregnancy and lactation (if women are recruited).
- Medications: Currently prescribed oral/IV corticosteroid treatment or loop diuretics (furosemide, bumetanide), antiplatelet and anticoagulation medication, methotrexate
- Mental capacity: Unable/unwilling to provide informed consent.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Devon and Exeter NHS Foundation Trust / University of Exeter
Exeter, Devon, EX2 5DW
About this study
Obesity is a major risk factor for Type 2 diabetes. However, two obese people of the same height and weight can have very different risks of the condition. As a greater proportion of the population is becoming obese, scientists need to understand more about why some people develop Type 2 diabetes at lower weight and why some people stay healthy despite being obese. The investigators and others provided evidence for genetic factors associated with higher weight for a given height but lower risk of diabetes, lower cholesterol and fat levels, lower blood pressure and lower risk of heart disease. The investigators showed that people who carry these genetic factors are able to store extra fat in a safe place, which is under the skin, as they gain weight. The proposed project aims to establish whether or not these genetic factors are associated with better development and function of fat tissue in storing extra fat. It is thought that a healthy and functional fat tissue in the human body has a key role in modifying the risk of diseases such as Type 2 diabetes, heart disease and hypertension.
Volunteers from Exeter 10,000 who gave their permission to contact them about further research will be recruited to the study. In those that agree, detailed body size measures, including body composition assessments by the BodPodTM machine will be recorded, a blood sample will be collected, and a small subcutaneous abdominal fat biopsy will be collected to measure fat cell size and from which a sample will be stored for future analyses. The results between people with and without the particular genetic changes of interest will be compared.
Knowing more about these genetic changes and how fat cells work could help to improve understanding of the factors that predispose, delay or protect obese individuals from Type 2 diabetes and other metabolic disturbances.
Read the detailed description
Introduction:
Diabetes is the most common chronic metabolic disease and is a major source of morbidity and mortality. It is one of the biggest healthcare challenges facing the United Kingdom's (UK) National Health Service (NHS) with more than 2.6 million adults diagnosed in the UK, with the vast majority (90%) having Type 2 diabetes (T2D). It is anticipated that the numbers will continue to rise, in part due to the increasing levels of obesity in the population.
Type 2 diabetes is characterised by high blood glucose levels in the context of increasing insulin resistance and reduced beta cell function, and this can develop over several years with individuals unaware of the problem.
Research groups in Exeter are leading efforts to identify the genetic factors that influence why some people develop Type 2 diabetes despite relative leanness, whilst many obese people do not get the disease. The investigators have identified many such factors but now wish to study them in more detail to understand the role of a healthy and functioning adipose tissue in the disease mechanism. This study builds on a previous 'recruit by genotype' study to explore the size of fat cells in people carrying the most genetic factors for being fatter but healthier (fATDIVA (for Adipose Tissue DIabetes VAriants) NCT02505321). The investigators will expand on the range of genetic variations to be undertaken in the research volunteers. The preliminary data from fATDIVA helped to secure prestigious funding from Diabetes UK to expand this work to improve understanding of the complex processes that lead to Type 2 diabetes.
The investigators are trying to understand how genetic variations cause differences in the human ability to store fat. The hypothesis to be tested is that individuals carrying different genetic variations have different abilities to store fat under the skin as subcutaneous fat tissue. This could lead to an improved understanding of subcutaneous fat storage. It is very unlikely that scientists will be able to reverse substantially the rising numbers of people becoming overweight or obese as they age, therefore this study's findings could be important in identifying how to reduce the risk of disease caused by obesity.
Study Design:
This is a prospective observational study that will take place over a 30 month period (March 2019 to August 2021).
Study participants:
All participants will be identified from existing research cohorts managed by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility (Exeter CRF) and recruitment will be facilitated within the Exeter CRF.
Under over-arching ethical approval 09/H0106/75, approximately 8900 anonymised DNA samples have whole genome genotype data.
Subject Selection:
The researchers will provide the Exeter Clinical Research Facility (Exeter CRF) with a list of the sample numbers that fulfil the inclusion criteria. The Exeter CRF will approach these individuals on the researcher's behalf to ask if they would be willing to provide body fat measures, a blood sample and an abdominal fat biopsy. Participants would be invited to a single visit lasting up to 2 hours at the Exeter CRF for data and sample collection.
Interested participants will then be contacted directly by a member of the study team who will be responsible for the recruitment process, providing more detailed verbal and written project-specific information.
The investigators will aim to target men only to increase power for two reasons. First, men and women have different body shape and different fat distribution. Men tend to store the extra fat in abdominal subcutaneous adipose tissue while women tend to store it in the lower body. Second, the study of fat biopsy samples in women could be affected by menopause which could cause bias in the data.
However, as the target sample size is 500 and the number of men who fulfil the inclusion criteria is approximately 3000, this will be reviewed after a year. If projections indicate that the target sample size will not be met, women will also be recruited in the second year.
- Conditions
- Diabetes Mellitus
- Being tested
- Abdominal fat biopsy
- Keywords
- Type 2 diabetes, adipocyte, adipocyte tissue dysfunction, adiposity, favourable adiposity, gene expression, adipose tissue
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 2, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abdominal fat biopsyProcedure or surgery
A sample of abdominal fat will be obtained by firstly injecting some local anaesthetic into an accessible area of the abdomen. Using a scalpel, a small incision (approx 2-3 cm) will be made to a depth of approx 15mm and two small pea-sized samples of fat will be removed. The wound will be closed with simple sutures or steristrips.
| Study group | Role | What they receive |
|---|---|---|
| Adipocyte measurement | Experimental | Abdominal fat biopsy Receives: Procedure: Abdominal fat biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean adipocyte size (µm2) assessed using Image J software.
ImageJ is a cross-platform image analysis tool developed to measure particle/cell size and will be used here to measure adipocyte size to test whether or not individuals carrying a high genetic load of "favourable adiposity" alleles have smaller subcutaneous fat cells.
Measured: Within 12 months of recruitment date of final participant
Secondary outcomes (3)
Adipose tissue expression of genes that are markers of adipogenesis (PPARy, CREBP).
This secondary outcome is the adipocytes' gene expression measures of adipogenesis.
Measured: Within 12 months of recruitment date of final participant
Adipose tissue expression of genes that are markers of fibrosis (SPARC, collagens, TGFbeta, LOX).
This secondary outcome is the adipocytes' gene expression measures of fibrosis.
Measured: Within 12 months of recruitment date of final participant
Adipose tissue expression of genes that are determinants of adipose inflammation (IL-1beta, IL-6, and 8, TNFalpha, MCP-1/CCL2).
This secondary outcome is the adipocytes' gene expression measures of adipose inflammation.
Measured: Within 12 months of recruitment date of final participant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2019
- Study start7 Mar 2019
- Primary completion20 May 2021
- Study completion20 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- Anthropometry: * Baseline data including Height (m), Weight (kg), Waist (cm) and Hip (cm) circumference will be recorded. * Skin fold measurements (mm) from biceps, triceps, subscapular, and suprailiac regions * Detailed body fat measures will be obtained from the BodPodTM. Medical history: • including current medications and lifestyle information (smoking/alcohol). Blood sample: • Up to 20 ml venous blood sample for HbA1c and storage for analysis of biomarkers of adiposity. Abdominal fat biopsy: for adipocyte measurements and store a sample for future analyses. A sample of abdominal fat will be obtained by firstly injecting some local anaesthetic into an accessible area of the abdomen. Using a scalpel, a small incision (approx 2-3 cm) will be made to a depth of approx15mm and two small pea-sized samples of fat will be removed. The wound will be closed with simple sutures or steristrips.
- Masking
- None (open label)
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Devon and Exeter NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Exeter, NIHR Exeter Clinical Research Facility
- Responsible party
- Sponsor
- Investigators
- Timothy Frayling, PhD, Principal investigator, University of Exeter
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04040595
- Sponsor's protocol ID
- IRAS: 257693
- Other IDs
- 105009, 19/SW/0012, 1909872
- Acronym
- FATFUNgenes
- Status last verified
- Jun 2021
- First submitted
- 12 Jun 2019
- Last updated
- 8 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S. The metabolically obese, normal-weight individual revisited. Diabetes. 1998 May;47(5):699-713. doi: 10.2337/diabetes.47.5.699.
PubMed 9588440Ruderman NB, Schneider SH, Berchtold P. The "metabolically-obese," normal-weight individual. Am J Clin Nutr. 1981 Aug;34(8):1617-21. doi: 10.1093/ajcn/34.8.1617.
PubMed 7270486Ji Y, Yiorkas AM, Frau F, Mook-Kanamori D, Staiger H, Thomas EL, Atabaki-Pasdar N, Campbell A, Tyrrell J, Jones SE, Beaumont RN, Wood AR, Tuke MA, Ruth KS, Mahajan A, Murray A, Freathy RM, Weedon MN, Hattersley AT, Hayward C, Machann J, Haring HU, Franks P, de Mutsert R, Pearson E, Stefan N, Frayling TM, Allebrandt KV, Bell JD, Blakemore AI, Yaghootkar H. Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension. Diabetes. 2019 Jan;68(1):207-219. doi: 10.2337/db18-0708. Epub 2018 Oct 23.
PubMed 30352878Yaghootkar H, Lotta LA, Tyrrell J, Smit RA, Jones SE, Donnelly L, Beaumont R, Campbell A, Tuke MA, Hayward C, Ruth KS, Padmanabhan S, Jukema JW, Palmer CC, Hattersley A, Freathy RM, Langenberg C, Wareham NJ, Wood AR, Murray A, Weedon MN, Sattar N, Pearson E, Scott RA, Frayling TM. Genetic Evidence for a Link Between Favorable Adiposity and Lower Risk of Type 2 Diabetes, Hypertension, and Heart Disease. Diabetes. 2016 Aug;65(8):2448-60. doi: 10.2337/db15-1671. Epub 2016 Apr 26.
PubMed 27207519Yaghootkar H, Scott RA, White CC, Zhang W, Speliotes E, Munroe PB, Ehret GB, Bis JC, Fox CS, Walker M, Borecki IB, Knowles JW, Yerges-Armstrong L, Ohlsson C, Perry JR, Chambers JC, Kooner JS, Franceschini N, Langenberg C, Hivert MF, Dastani Z, Richards JB, Semple RK, Frayling TM. Genetic evidence for a normal-weight "metabolically obese" phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes. Diabetes. 2014 Dec;63(12):4369-77. doi: 10.2337/db14-0318. Epub 2014 Jul 21.
PubMed 25048195Lotta LA, Gulati P, Day FR, Payne F, Ongen H, van de Bunt M, Gaulton KJ, Eicher JD, Sharp SJ, Luan J, De Lucia Rolfe E, Stewart ID, Wheeler E, Willems SM, Adams C, Yaghootkar H; EPIC-InterAct Consortium; Cambridge FPLD1 Consortium; Forouhi NG, Khaw KT, Johnson AD, Semple RK, Frayling T, Perry JR, Dermitzakis E, McCarthy MI, Barroso I, Wareham NJ, Savage DB, Langenberg C, O'Rahilly S, Scott RA. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet. 2017 Jan;49(1):17-26. doi: 10.1038/ng.3714. Epub 2016 Nov 14.
PubMed 27841877Scott RA, Fall T, Pasko D, Barker A, Sharp SJ, Arriola L, Balkau B, Barricarte A, Barroso I, Boeing H, Clavel-Chapelon F, Crowe FL, Dekker JM, Fagherazzi G, Ferrannini E, Forouhi NG, Franks PW, Gavrila D, Giedraitis V, Grioni S, Groop LC, Kaaks R, Key TJ, Kuhn T, Lotta LA, Nilsson PM, Overvad K, Palli D, Panico S, Quiros JR, Rolandsson O, Roswall N, Sacerdote C, Sala N, Sanchez MJ, Schulze MB, Siddiq A, Slimani N, Sluijs I, Spijkerman AM, Tjonneland A, Tumino R, van der A DL, Yaghootkar H; RISC study group; EPIC-InterAct consortium; McCarthy MI, Semple RK, Riboli E, Walker M, Ingelsson E, Frayling TM, Savage DB, Langenberg C, Wareham NJ. Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity. Diabetes. 2014 Dec;63(12):4378-4387. doi: 10.2337/db14-0319. Epub 2014 Jun 19.
PubMed 24947364Alkhouli N, Mansfield J, Green E, Bell J, Knight B, Liversedge N, Tham JC, Welbourn R, Shore AC, Kos K, Winlove CP. The mechanical properties of human adipose tissues and their relationships to the structure and composition of the extracellular matrix. Am J Physiol Endocrinol Metab. 2013 Dec;305(12):E1427-35. doi: 10.1152/ajpendo.00111.2013. Epub 2013 Oct 8.
PubMed 24105412Acosta JR, Douagi I, Andersson DP, Backdahl J, Ryden M, Arner P, Laurencikiene J. Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes. Diabetologia. 2016 Mar;59(3):560-70. doi: 10.1007/s00125-015-3810-6. Epub 2015 Nov 25.
PubMed 26607638
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Genetics of Adipose Tissue Function and Its Link to Type 2 Diabetes and Heart Disease
- ClinicalTrials.gov ID
- NCT04040595
- Acronym / sponsor ID
- FATFUNgenes / IRAS: 257693
- Conditions
- Diabetes Mellitus
- Keywords
- Type 2 diabetes, adipocyte, adipocyte tissue dysfunction, adiposity, favourable adiposity, gene expression, adipose tissue
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- Royal Devon and Exeter NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Exeter, NIHR Exeter Clinical Research Facility
- Study start
- 7 Mar 2019 (actual)
- Primary completion
- 20 May 2021 (actual)
- Study completion
- 20 May 2021 (actual)
- First posted
- 31 Jul 2019 (actual)
- 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.
Obesity is a major risk factor for Type 2 diabetes. However, two obese people of the same height and weight can have very different risks of the condition. As a greater proportion of the population is becoming obese, scientists need to understand more about why some people develop Type 2 diabetes at lower weight and why some people stay healthy despite being obese. The investigators and others provided evidence for genetic factors associated with higher weight for a given height but lower risk of diabetes, lower cholesterol and fat levels, lower blood pressure and lower risk of heart disease. The investigators showed that people who carry these genetic factors are able to store extra fat in a safe place, which is under the skin, as they gain weight. The proposed project aims to establish whether or not these genetic factors are associated with better development and function of fat tissue in storing extra fat. It is thought that a healthy and functional fat tissue in the human body has a key role in modifying the risk of diseases such as Type 2 diabetes, heart disease and hypertension.
Volunteers from Exeter 10,000 who gave their permission to contact them about further research will be recruited to the study. In those that agree, detailed body size measures, including body composition assessments by the BodPodTM machine will be recorded, a blood sample will be collected, and a small subcutaneous abdominal fat biopsy will be collected to measure fat cell size and from which a sample will be stored for future analyses. The results between people with and without the particular genetic changes of interest will be compared.
Knowing more about these genetic changes and how fat cells work could help to improve understanding of the factors that predispose, delay or protect obese individuals from Type 2 diabetes and other metabolic disturbances.
Detailed description
Introduction:
Diabetes is the most common chronic metabolic disease and is a major source of morbidity and mortality. It is one of the biggest healthcare challenges facing the United Kingdom's (UK) National Health Service (NHS) with more than 2.6 million adults diagnosed in the UK, with the vast majority (90%) having Type 2 diabetes (T2D). It is anticipated that the numbers will continue to rise, in part due to the increasing levels of obesity in the population.
Type 2 diabetes is characterised by high blood glucose levels in the context of increasing insulin resistance and reduced beta cell function, and this can develop over several years with individuals unaware of the problem.
Research groups in Exeter are leading efforts to identify the genetic factors that influence why some people develop Type 2 diabetes despite relative leanness, whilst many obese people do not get the disease. The investigators have identified many such factors but now wish to study them in more detail to understand the role of a healthy and functioning adipose tissue in the disease mechanism. This study builds on a previous 'recruit by genotype' study to explore the size of fat cells in people carrying the most genetic factors for being fatter but healthier (fATDIVA (for Adipose Tissue DIabetes VAriants) NCT02505321). The investigators will expand on the range of genetic variations to be undertaken in the research volunteers. The preliminary data from fATDIVA helped to secure prestigious funding from Diabetes UK to expand this work to improve understanding of the complex processes that lead to Type 2 diabetes.
The investigators are trying to understand how genetic variations cause differences in the human ability to store fat. The hypothesis to be tested is that individuals carrying different genetic variations have different abilities to store fat under the skin as subcutaneous fat tissue. This could lead to an improved understanding of subcutaneous fat storage. It is very unlikely that scientists will be able to reverse substantially the rising numbers of people becoming overweight or obese as they age, therefore this study's findings could be important in identifying how to reduce the risk of disease caused by obesity.
Study Design:
This is a prospective observational study that will take place over a 30 month period (March 2019 to August 2021).
Study participants:
All participants will be identified from existing research cohorts managed by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility (Exeter CRF) and recruitment will be facilitated within the Exeter CRF.
Under over-arching ethical approval 09/H0106/75, approximately 8900 anonymised DNA samples have whole genome genotype data.
Subject Selection:
The researchers will provide the Exeter Clinical Research Facility (Exeter CRF) with a list of the sample numbers that fulfil the inclusion criteria. The Exeter CRF will approach these individuals on the researcher's behalf to ask if they would be willing to provide body fat measures, a blood sample and an abdominal fat biopsy. Participants would be invited to a single visit lasting up to 2 hours at the Exeter CRF for data and sample collection.
Interested participants will then be contacted directly by a member of the study team who will be responsible for the recruitment process, providing more detailed verbal and written project-specific information.
The investigators will aim to target men only to increase power for two reasons. First, men and women have different body shape and different fat distribution. Men tend to store the extra fat in abdominal subcutaneous adipose tissue while women tend to store it in the lower body. Second, the study of fat biopsy samples in women could be affected by menopause which could cause bias in the data.
However, as the target sample size is 500 and the number of men who fulfil the inclusion criteria is approximately 3000, this will be reviewed after a year. If projections indicate that the target sample size will not be met, women will also be recruited in the second year.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Anthropometry: * Baseline data including Height (m), Weight (kg), Waist (cm) and Hip (cm) circumference will be recorded. * Skin fold measurements (mm) from biceps, triceps, subscapular, and suprailiac regions * Detailed body fat measures will be obtained from the BodPodTM. Medical history: • including current medications and lifestyle information (smoking/alcohol). Blood sample: • Up to 20 ml venous blood sample for HbA1c and storage for analysis of biomarkers of adiposity. Abdominal fat biopsy: for adipocyte measurements and store a sample for future analyses. A sample of abdominal fat will be obtained by firstly injecting some local anaesthetic into an accessible area of the abdomen. Using a scalpel, a small incision (approx 2-3 cm) will be made to a depth of approx15mm and two small pea-sized samples of fat will be removed. The wound will be closed with simple sutures or steristrips.
| Arm | Type | Receives |
|---|---|---|
| Adipocyte measurement | Experimental | Procedure: Abdominal fat biopsyAbdominal fat biopsy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Demographics: Age 18-75 inclusive
- Ethnicity: Reflective of local demographic
- Mental capacity: Willing and able to provide informed consent
Key exclusion criteria (3 listed)
- Medical history: History of bariatric surgery and recent significant weight loss/gain (+/- 3 kgs/ half a stone in the last 3 months); connective tissue disease, pregnancy and lactation (if women are recruited).
- Medications: Currently prescribed oral/IV corticosteroid treatment or loop diuretics (furosemide, bumetanide), antiplatelet and anticoagulation medication, methotrexate
- Mental capacity: Unable/unwilling to provide informed consent.
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 |
|---|---|---|
| Abdominal fat biopsyA sample of abdominal fat will be obtained by firstly injecting some local anaesthetic into an accessible area of the abdomen. Using a scalpel, a small incision (approx 2-3 cm) will be made to a depth of approx 15mm and two small pea-sized samples of fat will be removed. The wound will be closed with simple sutures or steristrips. | Procedure or surgery | Adipocyte measurement |
Primary outcome
Mean adipocyte size (µm2) assessed using Image J software.
Time frame: Within 12 months of recruitment date of final participant
ImageJ is a cross-platform image analysis tool developed to measure particle/cell size and will be used here to measure adipocyte size to test whether or not individuals carrying a high genetic load of "favourable adiposity" alleles have smaller subcutaneous fat cells.
3 secondary outcomes
Adipose tissue expression of genes that are markers of adipogenesis (PPARy, CREBP).
Time frame: Within 12 months of recruitment date of final participant
Adipose tissue expression of genes that are markers of fibrosis (SPARC, collagens, TGFbeta, LOX).
Time frame: Within 12 months of recruitment date of final participant
Adipose tissue expression of genes that are determinants of adipose inflammation (IL-1beta, IL-6, and 8, TNFalpha, MCP-1/CCL2).
Time frame: Within 12 months of recruitment date of final participant
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 8 Jun 2021.
- Background: PubMed 9588440Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S. The metabolically obese, normal-weight individual revisited. Diabetes. 1998 May;47(5):699-713. doi: 10.2337/diabetes.47.5.699.
- Background: PubMed 7270486Ruderman NB, Schneider SH, Berchtold P. The "metabolically-obese," normal-weight individual. Am J Clin Nutr. 1981 Aug;34(8):1617-21. doi: 10.1093/ajcn/34.8.1617.
- Background: PubMed 30352878Ji Y, Yiorkas AM, Frau F, Mook-Kanamori D, Staiger H, Thomas EL, Atabaki-Pasdar N, Campbell A, Tyrrell J, Jones SE, Beaumont RN, Wood AR, Tuke MA, Ruth KS, Mahajan A, Murray A, Freathy RM, Weedon MN, Hattersley AT, Hayward C, Machann J, Haring HU, Franks P, de Mutsert R, Pearson E, Stefan N, Frayling TM, Allebrandt KV, Bell JD, Blakemore AI, Yaghootkar H. Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension. Diabetes. 2019 Jan;68(1):207-219. doi: 10.2337/db18-0708. Epub 2018 Oct 23.
- Background: PubMed 27207519Yaghootkar H, Lotta LA, Tyrrell J, Smit RA, Jones SE, Donnelly L, Beaumont R, Campbell A, Tuke MA, Hayward C, Ruth KS, Padmanabhan S, Jukema JW, Palmer CC, Hattersley A, Freathy RM, Langenberg C, Wareham NJ, Wood AR, Murray A, Weedon MN, Sattar N, Pearson E, Scott RA, Frayling TM. Genetic Evidence for a Link Between Favorable Adiposity and Lower Risk of Type 2 Diabetes, Hypertension, and Heart Disease. Diabetes. 2016 Aug;65(8):2448-60. doi: 10.2337/db15-1671. Epub 2016 Apr 26.
- Background: PubMed 25048195Yaghootkar H, Scott RA, White CC, Zhang W, Speliotes E, Munroe PB, Ehret GB, Bis JC, Fox CS, Walker M, Borecki IB, Knowles JW, Yerges-Armstrong L, Ohlsson C, Perry JR, Chambers JC, Kooner JS, Franceschini N, Langenberg C, Hivert MF, Dastani Z, Richards JB, Semple RK, Frayling TM. Genetic evidence for a normal-weight "metabolically obese" phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes. Diabetes. 2014 Dec;63(12):4369-77. doi: 10.2337/db14-0318. Epub 2014 Jul 21.
- Background: PubMed 27841877Lotta LA, Gulati P, Day FR, Payne F, Ongen H, van de Bunt M, Gaulton KJ, Eicher JD, Sharp SJ, Luan J, De Lucia Rolfe E, Stewart ID, Wheeler E, Willems SM, Adams C, Yaghootkar H; EPIC-InterAct Consortium; Cambridge FPLD1 Consortium; Forouhi NG, Khaw KT, Johnson AD, Semple RK, Frayling T, Perry JR, Dermitzakis E, McCarthy MI, Barroso I, Wareham NJ, Savage DB, Langenberg C, O'Rahilly S, Scott RA. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet. 2017 Jan;49(1):17-26. doi: 10.1038/ng.3714. Epub 2016 Nov 14.
- Background: PubMed 24947364Scott RA, Fall T, Pasko D, Barker A, Sharp SJ, Arriola L, Balkau B, Barricarte A, Barroso I, Boeing H, Clavel-Chapelon F, Crowe FL, Dekker JM, Fagherazzi G, Ferrannini E, Forouhi NG, Franks PW, Gavrila D, Giedraitis V, Grioni S, Groop LC, Kaaks R, Key TJ, Kuhn T, Lotta LA, Nilsson PM, Overvad K, Palli D, Panico S, Quiros JR, Rolandsson O, Roswall N, Sacerdote C, Sala N, Sanchez MJ, Schulze MB, Siddiq A, Slimani N, Sluijs I, Spijkerman AM, Tjonneland A, Tumino R, van der A DL, Yaghootkar H; RISC study group; EPIC-InterAct consortium; McCarthy MI, Semple RK, Riboli E, Walker M, Ingelsson E, Frayling TM, Savage DB, Langenberg C, Wareham NJ. Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity. Diabetes. 2014 Dec;63(12):4378-4387. doi: 10.2337/db14-0319. Epub 2014 Jun 19.
- Background: PubMed 24105412Alkhouli N, Mansfield J, Green E, Bell J, Knight B, Liversedge N, Tham JC, Welbourn R, Shore AC, Kos K, Winlove CP. The mechanical properties of human adipose tissues and their relationships to the structure and composition of the extracellular matrix. Am J Physiol Endocrinol Metab. 2013 Dec;305(12):E1427-35. doi: 10.1152/ajpendo.00111.2013. Epub 2013 Oct 8.
- Background: PubMed 26607638Acosta JR, Douagi I, Andersson DP, Backdahl J, Ryden M, Arner P, Laurencikiene J. Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes. Diabetologia. 2016 Mar;59(3):560-70. doi: 10.1007/s00125-015-3810-6. Epub 2015 Nov 25.
- Individual participant dataSharing planned: No
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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.
Timothy Frayling, PhD principal investigator
University of Exeter
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Abdominal fat biopsy in people with Diabetes Mellitus, run by Royal Devon and Exeter NHS Foundation Trust at 1 site in United Kingdom.
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 3 inclusion and 3 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 8 Jun 2021. 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 United Kingdom. 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.
What does the primary outcome measure?
Mean adipocyte size (µm2) assessed using Image J software. (time frame: Within 12 months of recruitment date of final participant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04040595, which also lists 9 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 8 Jun 2021.