Defining the Molecular and Physiological Mechanisms of Pancreatic Islet Cell Dysfunction Which Lead to Type 2 Diabetes
DIVA-Exeter
3 other identifiers
interventional
328
1 country
2
Brief Summary
Defects in insulin secretion are central to the pathogenesis of type 2 diabetes (T2D) but the molecular basis and physiological consequences of those defects are poorly understood, impeding efforts to develop novel therapeutic approaches. Key questions remain unanswered, such as the extent to which T2D-associated islet dysfunction reflects endogenous defects in beta-cell mass or function, as opposed to disruption of external factors impinging on the beta-cells, such as incretins. Recently the investigators have identified several genetic variations (DNA changes) associated with the production and processing of insulin in non-diabetic individuals and now aim to explore in more detail the role of these genetic variations. Utilising a "recruit by genotype" approach, they will identify individuals with and without genetic variants of interest from existing databases of research volunteers. The investigators will collect detailed medical history and measurements, fasted and stimulated blood samples for the profiling of insulin-related hormones and metabolites. The resulting genetic and non-genetic data will be used to improve understanding of the role of genetic variation on insulin secretion and sensitivity defects that lead to the development of T2D.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable diabetes-mellitus
Started Mar 2015
Longer than P75 for not_applicable diabetes-mellitus
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 4, 2015
CompletedFirst Submitted
Initial submission to the registry
July 6, 2015
CompletedFirst Posted
Study publicly available on registry
July 22, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2019
CompletedSeptember 25, 2019
September 1, 2019
4.1 years
July 6, 2015
September 24, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximal Insulin Secretion (composite measure) following formal stimulation (GPAIS) test
Maximal insulin secretion will be assessed using composite measures of insulin, proinsulin, C-peptide, glucose, etc., from biological samples.
Within 12 months of recruitment date of final participant
Secondary Outcomes (1)
Faecal elastase
Within 12 months of recruitment date of final participant
Study Arms (2)
DIVA-1 CCND2
EXPERIMENTALIndividuals carrying a genetic change in the CCND2 gene and controls matched for gender, age and BMI. Participants will undergo the Glucose-Potentiated Arginine-Induced Insulin Secretion (GPAIS) test plus optional faecal elastase measurement. Case/control status will be unblinded at analysis.
DIVA-2 Low Risk of Diabetes
EXPERIMENTALIndividuals carrying the fewest genetic risk alleles for diabetes and controls carrying the average number of genetic risk alleles, matched for gender, age and BMI. Participants will undergo the Glucose-Potentiated Arginine-Induced Insulin Secretion (GPAIS) test plus optional faecal elastase measurement. Case/control status will be unblinded at analysis.
Interventions
Intravenous catheters are inserted into antecubital veins in both arms. One arm is used for infusion of glucose/amino acid (Arginine). The other arm is used for intermittent sampling.
Eligibility Criteria
You may qualify if:
- Demographics: Adult, age 16-75 inclusive
- Ethnicity: Reflective of local demographic
- Mental capacity: Capacity to consent
You may not qualify if:
- Demographics: \<16 and \>75 years old
- Medical history: Bariatric surgery; history of recent significant weight loss (\>10% of weight in last year); known cardiovascular disease (previous myocardial infarction, stroke, angina or heart failure); glucose-galactose malabsorption syndrome; allergy to corn (maize)
- Medications: Currently prescribed glucose-lowering medication, oral/IV corticosteroid treatment or loop diuretics (furosemide, bumetanide)
- Mental capacity: Incapacity to consent
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Royal Devon and Exeter NHS Foundation Trustlead
- University of Exetercollaborator
- University of Oxfordcollaborator
- Oxford University Hospitals NHS Trustcollaborator
Study Sites (2)
University of Exeter
Exeter, Devon, EX2 5DW, United Kingdom
University of Oxford
Oxford, Oxfordshire, OX3 7LE, United Kingdom
Related Publications (2)
Kahn SE, Carr DB, Faulenbach MV, Utzschneider KM. An examination of beta-cell function measures and their potential use for estimating beta-cell mass. Diabetes Obes Metab. 2008 Nov;10 Suppl 4:63-76. doi: 10.1111/j.1463-1326.2008.00945.x.
PMID: 18834434BACKGROUNDLarsson H, Ahren B. Glucose-dependent arginine stimulation test for characterization of islet function: studies on reproducibility and priming effect of arginine. Diabetologia. 1998 Jul;41(7):772-7. doi: 10.1007/s001250050986.
PMID: 9686917BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Timothy M Frayling (Prof), PhD
University of Exeter
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- 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
March 4, 2015
Primary Completion
March 31, 2019
Study Completion
August 31, 2019
Last Updated
September 25, 2019
Record last verified: 2019-09
Data Sharing
- IPD Sharing
- Will not share