Abstract
BackgroundThe 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.MethodsComplete 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.ResultsThe 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.ConclusionDespite 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.
Highlights
The transcription factor-7-like-2 (TCF7L2) gene has been consistently associated with type 2 diabetes mellitus (T2D) [1] in different ethnic groups [2,3], and with fasting glucose levels [4]
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
Our study indicates that the rs7903146-T allele in transcription factor 7-like 2 (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
Summary
The transcription factor-7-like-2 (TCF7L2) gene has been consistently associated with type 2 diabetes mellitus (T2D) [1] in different ethnic groups [2,3], and with fasting glucose levels [4]. In genome-wide association studies (GWAS), the rs7903146-T allele located in an intronic region of the TCF7L2 gene has been associated with a higher risk of T2D [9,10,11] via mechanisms other than higher/lower TCF7L2 mRNA expression levels [12,13]. This allele has been associated with impaired β-cell function [14] and impaired insulin secretion [7]. 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. The purpose of the present study was to investigate the associations of rs7903146 with glycemia and glycemic variability in middle-aged participants without diabetes
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