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Completed

NCT Number: NCT03998111

Genetic Variation in CLTCL1 and Whole-body Glucose Control

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.

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Key information

Conditions

Glucose Control

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department for Health, University of Bath

Bath, BA2 7AY, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Oral glucose tolerance test

Diagnostic 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.

Primary outcomes

  1. Plasma glucose incremental area under the curve (CHC22 genotype)

    Time frame: 2 hours

    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. Peak plasma glucose (CHC22 genotype)

    Time frame: 2 hours

    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.

Secondary outcomes

  1. Fasting plasma glucose concentrations (CHC22 genotype)

    Time frame: 2 hours

    Plasma glucose will be measured at baseline and will be grouped by CHC22 genotype.

  2. Plasma glucose incremental area under the curve (other genotypes)

    Time frame: 2 hours

    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.

  3. Fasting plasma glucose concentrations (other genotypes)

    Time frame: 2 hours

    Plasma glucose will be measured at baseline and will be grouped by genotypes related to glucose control and sweet taste sensitivity.

  4. Matsuda insulin sensitivity index

    Time frame: 2 hours

    Matsuda insulin sensitivity index will be calculated using blood samples collected in the 2-hour postprandial period.

  5. Homeostasis model of insulin resistance

    Time frame: 2 hours

    Homeostasis model of insulin resistance will be calculated using blood samples collected in the 2-hour postprandial period.

Sponsors and collaborators

Lead sponsor

Javier Gonzalez

Other

Collaborators

  • University College, London

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2022
Study completion
2022
First posted
Jun 26, 2019
Registry last updated
May 4, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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