title: Association between the rs7903146 Polymorphism in the TCF7L2 Gene and Parameters Derived with Continuous Glucose Monitoring in Individuals without Diabetes.
abstract: BACKGROUND
  The rs7903146-T allele in the transcription factor 7-like 2 (TCF7L2) gene has been associated with impaired pancreatic insulin secretion, enhanced liver glucose production, and an increased risk of type 2 diabetes. Nevertheless, the impact of rs7903146 on daily glucose trajectories remains unclear. Continuous glucose monitoring (CGM) can estimate glycemia and glycemic variability based on consecutive glucose measurements collected over several days. The purpose of the present study was to investigate the associations of rs7903146 with glycemia and glycemic variability in middle-aged participants without diabetes.
  
  
  METHODS
  Complete data from 235 participants without diabetes from the Leiden Longevity Study were available. Participants were divided into two groups based on rs7903146 genotype; rs7903146-CC genotype carriers (N = 123) and rs7903146-CT/TT genotype carriers (N = 112). Validated parameters of glycemia (e.g., mean 24h glucose level) and glycemic variability (e.g., 24h standard deviation) were derived from data collected with a CGM system for a 72-hour period.
  
  
  RESULTS
  The study population was on average 64.7 years old (standard deviation = 5.9) and composed of 49.8% of women. Compared with rs7903146-CC carriers, rs7903146-CT/TT carriers exhibited a trend towards a higher mean 24-hour glucose level (5.21 versus 5.32 mmol/L; p-value = 0.15) and a significantly higher mean nocturnal glucose (3:00am- 6:00am; 4.48 versus 4.67 mmol/L; p-value = 0.03) that was explained for 34.6% by body weight and percentage body fat. No differences in measures of glycemic variability between the genotype groups were observed.
  
  
  CONCLUSIONS
  Despite limited sample size, our study indicates that the rs7903146-T allele in TCF7L2 was associated with a higher mean nocturnal glucose dependent on body composition, which might suggest that rs7902146 affects liver-specific aspects of glucose metabolism.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Sabrina
authors.initials: S
authors.lastname: van der Kroef
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Raymond
authors.initials: R
authors.lastname: Noordam
authors.affiliation: Section of Molecular Epidemiology, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Joris
authors.initials: J
authors.lastname: Deelen
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Abimbola A
authors.initials: AA
authors.lastname: Akintola
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Steffy W M
authors.initials: SW
authors.lastname: Jansen
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Iris
authors.initials: I
authors.lastname: Postmus
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Carolien A
authors.initials: CA
authors.lastname: Wijsman
authors.affiliation: Section of Molecular Epidemiology, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Beekman
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mooijaart
authors.affiliation: Section of Molecular Epidemiology, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
mesh_terms: D001483:Base Sequence; D001786:Blood Glucose / Q000235:genetics*; D015190:Blood Glucose Self-Monitoring; D001823:Body Composition / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
chemical_list: D001786:Blood Glucose; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D005947:Glucose