Genetic Variation in CLTCL1 and Whole-body Glucose Control

Glucose Control Clinical Trial

Official title:

The Role of Genetic Variation in CLTCL1 and Other Related Genes in Relation to Whole-body Glucose Control: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03998111
• Other study ID #: EP 17/18 252
• Status: Completed
• Phase: N/A
• Start date: October 1, 2018
• Est. completion date: March 1, 2022

Study information

• Verified date: May 2022
• Source: University of Bath
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: March 1, 2022
• Est. primary completion date: February 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Glucose Control

Intervention

Diagnostic Test:
• Oral glucose tolerance test
Participants will ingest 75 g anhydrous glucose dissolved in water and the blood responses will be measured over the following 2-hours using a venous cannula.

Locations

Country	Name	City	State
United Kingdom	Department for Health, University of Bath	Bath

Sponsors (2)

Lead Sponsor	Collaborator
Javier Gonzalez	University College, London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma glucose incremental area under the curve (CHC22 genotype)	Plasma glucose samples will be obtained throughout the 2-hour postprandial period and the incremental area under the curve will be calculated, this will be grouped by CHC22 genotype.	2 hours
Primary	Peak plasma glucose (CHC22 genotype)	Plasma glucose samples will be obtained throughout the 2-hour postprandial period and the peak glucose concentration will be measured, this will be grouped by CHC22 genotype.	2 hours
Secondary	Fasting plasma glucose concentrations (CHC22 genotype)	Plasma glucose will be measured at baseline and will be grouped by CHC22 genotype.	2 hours
Secondary	Plasma glucose incremental area under the curve (other genotypes)	Plasma glucose samples will be obtained throughout the 2-hour postprandial period and the incremental area under the curve will be calculated, this will be grouped by genotyping other genes related to glucose control or sweet taste sensitivity.	2 hours
Secondary	Fasting plasma glucose concentrations (other genotypes)	Plasma glucose will be measured at baseline and will be grouped by genotypes related to glucose control and sweet taste sensitivity.	2 hours
Secondary	Matsuda insulin sensitivity index	Matsuda insulin sensitivity index will be calculated using blood samples collected in the 2-hour postprandial period.	2 hours
Secondary	Homeostasis model of insulin resistance	Homeostasis model of insulin resistance will be calculated using blood samples collected in the 2-hour postprandial period.	2 hours