Postprandial lipemia and its relation to TCF7L2 gene polymorphisms in normoglycemic first-degree relatives of type 2 diabetes patients

Mishra, B.K.; Velmurugan, Muthusamy; Gambhir, Jasvinder K.; Madhu, Sri Venkata

doi:10.1007/s13410-018-0678-2

Cited by 5 publications

(5 citation statements)

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“…Also, healthy subjects with T allele with PUFA intake of more than 7.36% were shown to have higher VLDL concentrations and postprandial triglyceride lipoproteins ( 21 ). However, there was no association of postprandial triglyceride levels with risk allele of TCF7L2 gene in healthy first degree relatives of diabetes patients who had NGT and a BMI < 25 Kg/m 2 ( 22 ). Each of these studies represented specific groups of subjects mostly healthy individuals without diabetes or prediabetes unlike in our study which included subjects with varying degree of glucose tolerance.…”

Section: Discussionmentioning

confidence: 95%

“…It is believed that these effects are secondary to an impairment in insulin secretion ( 10 , 15 ). The role of TCF7L2 gene in modulating lipid metabolism is a less well studied area although these are mentioned in literature ( 19 – 22 , 38 , 39 )…”

Section: Discussionmentioning

confidence: 99%

“…The significantly higher PPTg levels in subjects with the T allele who also displayed greater insulin resistance and a higher risk of glucose intolerance clearly indicate that the risk allele of this gene is associated with PPTg dysmetabolism. After thorough research of the literature, only 5-6 studies could be identified which investigated the influence of TCF7L2 gene with respect to postprandial lipemia ( 19 – 21 , 30 , 38 , 41 ). Association of T allele of rs7903146 polymorphic form of TCF7L2 gene and postprandial hypertriglyceridemia was reported by Martinez et al.…”

Section: Discussionmentioning

confidence: 99%

“…In an earlier study, variants of TCF7L2 were found to modulate postprandial triglycerides levels in individuals with polyunsaturated fatty acid (PUFA) intakes of more than 7.36% (21). However, one of the studies conducted at our institute in subjects with normal glucose tolerance (NGT) did not show a significant difference in postprandial hypertriglyceridemia between the risk allele and wild type variants of this gene in first degree relatives of diabetes patients who had NGT and lower BMI (30). Decreased adipogenesis due to altered TCF7L2 gene (11) function may result into impaired Tg trapping and PPHTg.…”

Section: Introductionmentioning

confidence: 93%

“…TCF7L2 gene also affects GLP1 production and gluconeogenesis ( 18 ). Very few studies have explored its effects on adipogenesis and lipid metabolism as a possible mechanism for the TCF7L2 gene associated risk of development of diabetes ( 19 – 22 ).…”

Section: Introductionmentioning

confidence: 99%

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TCF7L2 gene associated postprandial triglyceride dysmetabolism- a novel mechanism for diabetes risk among Asian Indians

et al. 2022

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AimTCF7L2 gene is believed to increase the risk of T2DM by its effects on insulin secretion. However, the exact mechanism of this enhanced risk is not clearly known. While TCF7L2 gene has been shown to affect lipid metabolism, these effects have remained largely unexplored in the context of diabetes risk.MethodsPostprandial lipid responses to a standardized fat challenge test were performed in 620 Asian Indian subjects (310 with NGT and 310 with T2DM/prediabetes) and compared between the risk and wild genotypes of the rs7903146 TCF7L2 gene. In 30 subjects scheduled to undergo abdominal surgery (10 each with NGT, Prediabetes and T2DM), adipocyte TCF7L2 gene expression was also performed by real time qPCR and confirmed by protein expression in western blot.ResultsT allele of rs7903146 TCF7L2 gene was confirmed as the risk allele for T2DM (OR=1.8(1.2-2.74), p=0.005). TT+CT genotypes of rs7903146 TCF7L2 gene showed significantly higher 4hrTg (p<0.01), TgAUC (p<0.01), peakTg (p<0.01) as well as higher postprandial plasma glucose (p=.006) levels and HOMA-IR (p=0.03) and significantly lower adiponectin levels (p=0.02) as compared to CC genotype. The expression of TCF7L2 gene in VAT was 11-fold higher in prediabetes group as compared to NGT (P<0.01) and 5.7-fold higher in T2DM group as compared to NGT group(P=0.003) and was significantly associated with PPTg and glucose levels.ConclusionThere is significant PPTg dysmetabolism associated with the risk allele of rs7903146 polymorphism as well as adipocyte expression of TCF7L2 gene. Significant upregulation of TCF7L2 gene expression in VAT that correlates with PPTg and glycaemia is also seen in Asian Indians with glucose intolerance. Modulation of PPTg metabolism by TCF7L2 gene and the resultant PPHTg may be a novel mechanism that contributes to its diabetes risk in them.

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Section: Discussionmentioning

confidence: 95%