Blood DNA methylation at TXNIP and glycemic changes in response to weight-loss diet interventions: the POUNDS lost trial

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

<div class="section"> <a class="named-anchor" id="S1">  </a> <h5 class="section-title" id="d17834354e206">Background:</h5> <p id="P3">Thioredoxin Interacting Protein ( <i>TXNIP</i>) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5’-cytosine-phosphate-guanine-3’ (CpG) site cg19693031 of <i>TXNIP</i> has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes. We hypothesize that baseline DNAm level at <i>TXNIP</i> in blood may be associated with glycemic traits and their changes in response to weight-loss diet interventions. </p> </div><div class="section"> <a class="named-anchor" id="S2">  </a> <h5 class="section-title" id="d17834354e220">Methods:</h5> <p id="P4">We included 639 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss diet intervention. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm level of <i>TXNIP</i> as the average methylation level over CpGs within 500 bp of cg19693031. Generalized linear regression models were used for main analyses. </p> </div><div class="section"> <a class="named-anchor" id="S3">  </a> <h5 class="section-title" id="d17834354e228">Results:</h5> <p id="P5">We found that higher regional DNAm at <i>TXNIP</i> was significantly correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline ( <i>P</i><0.05 for all). Significant interactions were observed between dietary protein intake and DNAm on changes in insulin ( <i>P</i>-interaction=0.007) and HOMA-IR ( <i>P</i>-interaction=0.009) at 6 months. In participants with the highest tertile of regional DNAm at <i>TXNIP</i>, average protein (15%) intake was associated with a greater reduction in insulin (β: −0.14; 95% CI: −0.24, −0.03; <i>P</i>=0.011) and HOMA-IR (β: −0.15; 95% CI: −0.26, −0.03; <i>P</i>=0.014) than high protein (25%) intake, whereas no significant associations were found in those with the lower tertiles ( <i>P</i>>0.05). The interaction was attenuated to be non-significant at 2 years, presumably related to decreasing adherence to the diet intervention. </p> </div><div class="section"> <a class="named-anchor" id="S4">  </a> <h5 class="section-title" id="d17834354e258">Conclusions:</h5> <p id="P6">Our data indicate that higher regional DNAm level at <i>TXNIP</i> was significantly associated with better fasting glucose, HbA1c, and HOMA-IR; and people with higher regional DNAm levels benefited more in insulin and HOMA-IR improvement by taking the average-protein weight-loss diet. </p> </div>

Related collections

Most cited references 40

Record: found
Abstract: not found
Article: not found

Cutadapt removes adapter sequences from high-throughput sequencing reads

Marcel Martin (2011)

0 comments Cited 8139 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.

D. Matthews, J Hosker, A Rudenski … (1985)

The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.