Genetic Variation in CLTCL1 and Whole-body Glucose Control

Javier Gonzalez

Status: Completed

Conditions: Glucose Control

Treatments: Diagnostic Test: Oral glucose tolerance test

Study type: Interventional

Funder types: Other

Identifiers

NCT03998111

EP 17/18 252

Details and patient eligibility

About

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.

Full 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.

Enrollment: 82 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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82 participants in 1 patient group

Trial

Experimental group

Description:

Participants will undergo one trial visit where they will ingest an oral glucose load diluted in solution (oral glucose tolerance test) and blood samples will be measured over the following 2-hours. The buffy coat layer from the baseline sample will be obtained to extract DNA.

Treatment:

Diagnostic Test: Oral glucose tolerance test