NCT02505321

Brief Summary

The adipose (fat) cells under the skin are where individuals store excess fat. The more excess fat they have, the more "strain" they put on these cells which then get bigger and don't work as well as they should. Having some fat under the skin is important. People who have a genetic defect which results in them having almost no fat under their skin have a very high risk of a condition called insulin resistance (where the body does not respond as well to insulin and blood sugar levels rise). This can lead to diabetes and heart disease despite them not being overweight. Scientists have only recently started to understand the importance of fat in insulin resistance and how people unable to store fat very well can have insulin resistance despite not being obese. The investigators have also recently discovered that small changes in a person's genetic code (their body's instruction manual) may also affect their ability to store fat and would like to explore this in more detail. To do this, they will recruit volunteers from the Exeter 10,000 study who gave permission to contact them about further research. The investigators will collect detailed body size measures and blood samples taken before and after a special drink that is high in fat (similar to a thick milk shake), then compare the results between people with and without the particular genetic changes of interest. Knowing more about these genetic changes and how fat cells work could help to improve understanding about why some people develop diabetes and heart disease despite a relatively normal BMI.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
304

participants targeted

Target at P75+ for not_applicable diabetes-mellitus

Timeline
Completed

Started May 2015

Typical duration for not_applicable diabetes-mellitus

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 29, 2015

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

July 6, 2015

Completed
16 days until next milestone

First Posted

Study publicly available on registry

July 22, 2015

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2017

Completed
Last Updated

June 21, 2018

Status Verified

June 1, 2018

Enrollment Period

2.4 years

First QC Date

July 6, 2015

Last Update Submit

June 19, 2018

Conditions

Diabetes Mellitus

Keywords

insulin resistancephysiologygeneticsgene variantspathogenesistype 2 diabetesfatpolygenic lipodystrophy

Outcome Measures

Primary Outcomes (1)

  • Level of Circulatory Lipids following Triglyceride stimulation test (OTTT) (mmol/L)

    Level of Circulatory Lipids will be assessed using measures of triglyceride levels from each post-prandial time point sample.

    Within 12 months of recruitment date of final participant

Secondary Outcomes (2)

  • Mean adipocyte size assessed using Image J

    Within 12 months of recruitment date of final participant

  • Incremental Area under the Curve NEFA levels (µmol/L)

    Within 12 months of recruitment date of final participant

Study Arms (2)

fATDIVA - OTTT (Cases)

EXPERIMENTAL

Individuals identified with the "polygenic lipodystrophy" genetic variants of interest will undergo the Oral Triglyceride Tolerance Test (OTTT) plus an abdominal fat biopsy (optional). Case/control status will be unblinded at analysis.

Other: Oral Triglyceride Tolerance Test (OTTT)Procedure: Abdominal fat biopsy (optional)

fATDIVA - OTTT (Controls)

EXPERIMENTAL

Control individuals carrying the average number of risk alleles and matched to individuals identified with the "polygenic lipodystrophy" genetic variants of interest for gender, age and BMI, will undergo the Oral Triglyceride Tolerance Test (OTTT) plus an abdominal fat biopsy (optional). Case/control status will be unblinded at analysis.

Other: Oral Triglyceride Tolerance Test (OTTT)Procedure: Abdominal fat biopsy (optional)

Interventions

Oral Triglyceride Tolerance Test (OTTT)OTHER

Participants consume a fatty drink. An intravenous catheter is inserted into the antecubital veins in one arm for intermittent sampling over the following 4 hours. The OTTT permits simple evaluation of postchallenge triglyceride levels and is acceptable to participants.

Also known as: OTTT
fATDIVA - OTTT (Cases)fATDIVA - OTTT (Controls)
Abdominal fat biopsy (optional)PROCEDURE

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.

fATDIVA - OTTT (Cases)fATDIVA - OTTT (Controls)

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Demographics: Age 18-75 inclusive
  • Ethnicity: Reflective of local demographic
  • Mental capacity: Willing and able to provide informed consent

You may not qualify if:

  • Medical history: Treated Diabetes (including insulin and GLP-1 analogues), 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.
  • Medications: Currently prescribed glucose-lowering medication (we will NOT exclude those controlling their diabetes with diet alone), oral/IV corticosteroid treatment or loop diuretics (furosemide, bumetanide), antiplatelet and anticoagulation medication, methotrexate
  • Mental capacity: Unable/unwilling to provide informed consent.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Exeter

Exeter, Devon, EX2 5DW, United Kingdom

Location

Related Publications (7)

  • Yaghootkar 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.

    PMID: 25048195BACKGROUND

  • Semple RK, Sleigh A, Murgatroyd PR, Adams CA, Bluck L, Jackson S, Vottero A, Kanabar D, Charlton-Menys V, Durrington P, Soos MA, Carpenter TA, Lomas DJ, Cochran EK, Gorden P, O'Rahilly S, Savage DB. Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. J Clin Invest. 2009 Feb;119(2):315-22. doi: 10.1172/JCI37432. Epub 2009 Jan 26.

    PMID: 19164855BACKGROUND

  • Stears A, O'Rahilly S, Semple RK, Savage DB. Metabolic insights from extreme human insulin resistance phenotypes. Best Pract Res Clin Endocrinol Metab. 2012 Apr;26(2):145-57. doi: 10.1016/j.beem.2011.09.003.

    PMID: 22498245BACKGROUND

  • Alkhouli 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.

    PMID: 24105412BACKGROUND

  • Karamanos BG, Thanopoulou AC, Roussi-Penesi DP. Maximal post-prandial triglyceride increase reflects post-prandial hypertriglyceridaemia and is associated with the insulin resistance syndrome. Diabet Med. 2001 Jan;18(1):32-9. doi: 10.1046/j.1464-5491.2001.00386.x.

    PMID: 11168339BACKGROUND

  • Carstensen M, Thomsen C, Hermansen K. Incremental area under response curve more accurately describes the triglyceride response to an oral fat load in both healthy and type 2 diabetic subjects. Metabolism. 2003 Aug;52(8):1034-7. doi: 10.1016/s0026-0495(03)00155-0.

    PMID: 12898469BACKGROUND

  • Mohanlal N, Holman RR. A standardized triglyceride and carbohydrate challenge: the oral triglyceride tolerance test. Diabetes Care. 2004 Jan;27(1):89-94. doi: 10.2337/diacare.27.1.89.

    PMID: 14693972BACKGROUND

MeSH Terms

Conditions

Diabetes MellitusInsulin ResistanceDiabetes Mellitus, Type 2Platelet Glycoprotein IV Deficiency

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesHyperinsulinism

Study Officials

  • Timothy M Frayling (Prof), PhD

    University of Exeter

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 6, 2015

First Posted

July 22, 2015

Study Start

May 29, 2015

Primary Completion

October 31, 2017

Study Completion

October 31, 2017

Last Updated

June 21, 2018

Record last verified: 2018-06

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)