Clinical trial NCT03998111: Genetic Variation in CLTCL1 and Whole-body Glucose Control
Official title: The Role of Genetic Variation in CLTCL1 and Other Related Genes in Relation to Whole-body Glucose Control: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glucose Control
Keywords: Glucose
Genetic variation
CHC22
CLTCL1
Lead sponsor: University of Bath
Sponsor class: OTHER
Collaborators: name: University College, London
First posted: 2019-06-26
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Maintaining stable blood glucose concentrations after eating has important implications for health. Individuals who are better able to maintain stable blood glucose concentrations after consuming carbohydrate have a lower risk of mortality from cardiovascular disease. Muscle is the primary tissue for glucose disposal following a meal, and responsiveness of this tissue to insulin is dictated by GLUT4 translocation to the muscle cell membrane. Clathrin heavy chain isoform 22 (CHC22) is a protein that plays a key role in intracellular GLUT4 action, and it may play an important role in whole-body glucose control. Genetic variation in the gene which codes for CHC22 may be able to explain differences in glucose control at the whole-body level.

Detailed description: The ability to maintain relatively stable blood glucose concentrations after eating has important implications for health. Individuals who are better able to maintain stable blood glucose concentrations after consuming carbohydrate have a lower risk of mortality and morbidity from cardiovascular disease. Muscle is the primary tissue for glucose disposal after a meal and the ability to tolerate a glucose load is largely dependent on the ability of muscle to respond to insulin by translocating the glucose transporter, GLUT4, to the muscle cell membrane, facilitating glucose import into muscle from the circulation. Therefore, by understanding the mechanisms that explain why some people are better able to maintain glucose control can give insight into how to target physiological pathways (such as muscle glucose uptake) to reduce disease risk and improve health.

Clathrins are cytoplasmic proteins that play essential roles in cell membrane trafficking pathways. Pilot data indicate that the clathrin heavy chain isoform 22 (CHC22) plays a key role in intracellular targeting of GLUT4 and may therefore play an important role in whole-body glucose control. Cell-based studies suggest that genetic variation in the CLTCL1 gene (which encodes for CHC22) at SNP rs1061325, influences GLUT4 retention. It is currently unknown whether genetic variation in CHC22 has consequences for whole-body glucose control in humans.

Eligibility criteria: Inclusion Criteria:

* Body mass index between 18.5-29.9 kg/m\^2
* Aged 18-65 years
* Able and willing to provide informed consent and safely comply with study procedures

Exclusion Criteria:

* Any reported condition or behaviour deemed either to pose undue personal risk to the participant or introduce bias
* Any diagnosed metabolic disease (e.g. type 1 or type 2 diabetes)
* Any reported use of substances which may pose undue personal risk to the participants or introduce bias into the experiment
* Lifestyle not conforming to standard sleep-wake cycle (e.g. shift worker)

Primary outcomes:
measure: Plasma glucose incremental area under the curve (CHC22 genotype)
timeFrame: 2 hours
measure: Peak plasma glucose (CHC22 genotype)
timeFrame: 2 hours
Secondary outcomes:
measure: Fasting plasma glucose concentrations (CHC22 genotype)
timeFrame: 2 hours
measure: Plasma glucose incremental area under the curve (other genotypes)
timeFrame: 2 hours
measure: Fasting plasma glucose concentrations (other genotypes)
timeFrame: 2 hours
measure: Matsuda insulin sensitivity index
timeFrame: 2 hours
measure: Homeostasis model of insulin resistance
timeFrame: 2 hours
Other outcomes:
Locations:
city: Bath
country: United Kingdom
facility: Department for Health, University of Bath
Study officials:
References: