Pistachio consumption modulates DNA oxidation and genes related to telomere maintenance: a crossover randomized clinical trial

Abstract

BackgroundTelomere attrition may play an important role in the pathogenesis and severity of type 2 diabetes (T2D), increasing the probability of β cell senescence and leading to reduced cell mass and decreased insulin secretion. Nutrition and lifestyle are known factors modulating the aging process and insulin resistance/secretion, determining the risk of T2D.ObjectivesThe aim of this study was to evaluate the effects of pistachio intake on telomere length and other cellular aging-related parameters of glucose and insulin metabolism.MethodsForty-nine prediabetic subjects were included in a randomized crossover clinical trial. Subjects consumed a pistachio-supplemented diet (PD, 50 E% [energy percentage] carbohydrates and 33 E% fat, including 57 g pistachios/d) and an isocaloric control diet (CD, 55 E% carbohydrates and 30 E% fat) for 4 mo each, separated by a 2-wk washout period. DNA oxidation was evaluated by DNA damage (via 8-hydroxydeoxyguanosine). Leucocyte telomere length and gene expression related to either oxidation, telomere maintenance or glucose, and insulin metabolism were analyzed by multiplexed quantitative reverse transcriptase-polymerase chain reaction after the dietary intervention.ResultsCompared with the CD, the PD reduced oxidative damage to DNA (mean: −3.5%; 95% CI: −8.07%, 1.05%; P = 0.009). Gene expression of 2 telomere-related genes (TERT and WRAP53) was significantly upregulated (164% and 53%) after the PD compared with the CD (P = 0.043 and P = 0.001, respectively). Interestingly, changes in TERT expression were negatively correlated to changes in fasting plasma glucose concentrations and in the homeostatic model assessment of insulin resistance.ConclusionsChronic pistachio consumption reduces oxidative damage to DNA and increases the gene expression of some telomere-associated genes. Lessening oxidative damage to DNA and telomerase expression through diet may represent an intriguing way to promote healthspan in humans, reversing certain deleterious metabolic consequences of prediabetes. This study was registered at clinicaltrials.gov as NCT01441921.

Nutritional Strategies in Prediabetes: A Scoping Review of Recent Evidence

“…Nuts are important sources of protein, especially for individuals practicing vegetarianism. The health effects of pistachio in prediabetes were studied extensively in the EPIRDEM trial [ 44 , 45 , 46 , 47 , 48 ]. Consumption of pistachio brought positive genetic changes in DNA damage, diabetes-related circulating miRNA and gene expression of some telomere-associated genes, leading to a healthier genetic profile [ 44 , 48 ].…”

“…The health effects of pistachio in prediabetes were studied extensively in the EPIRDEM trial [ 44 , 45 , 46 , 47 , 48 ]. Consumption of pistachio brought positive genetic changes in DNA damage, diabetes-related circulating miRNA and gene expression of some telomere-associated genes, leading to a healthier genetic profile [ 44 , 48 ]. Pistachio also demonstrated positive correlations with glucose and insulin related parameters, urine metabolites and creatinine levels in prediabetes [ 44 , 45 , 47 ].…”

“…Consumption of pistachio brought positive genetic changes in DNA damage, diabetes-related circulating miRNA and gene expression of some telomere-associated genes, leading to a healthier genetic profile [ 44 , 48 ]. Pistachio also demonstrated positive correlations with glucose and insulin related parameters, urine metabolites and creatinine levels in prediabetes [ 44 , 45 , 47 ]. However, except for small LDL particles and non-HDL particles [ 46 ], there were no significant improvements in lipid profile and inflammatory risk factors [ 45 ].…”

“…Understandably, the most assessed parameter was plasma glucose, often interpreted as FPG and/or two-hour postprandial glucose (2hPG) measured via an oral glucose tolerance test (OGTT). Of 79 studies investigating plasma glucose levels, 48 (60.8%) found significant improvements in one or more of the following categories: FPG, 2hPG and area under the postprandial curve (AUC) over variable timeframes up to 180 min [ 17 , 18 , 19 , 20 , 21 , 23 , 24 , 25 , 26 , 27 , 28 , 31 , 32 , 33 , 37 , 38 , 40 , 41 , 44 , 49 , 50 , 52 , 57 , 58 , 59 , 60 , 61 , 62 , 64 , 65 , 74 , 76 , 78 , 79 , 81 , 85 , 88 , 90 , 93 , 98 , 102 , 103 , 105 , 107 , 108 , 109 , 110 , 111 ]. Likewi...…”

“…Among computed values derived from glucose and insulin measurements, the homeostatic model assessment of insulin resistance (HOMA-IR score) was most frequently reported with 41 studies, of which 26 (63.4%) demonstrated significant improvement with intervention [ 17 , 18 , 19 , 21 , 23 , 24 , 28 , 31 , 33 , 36 , 44 , 49 , 53 , 58 , 59 , 62 , 76 , 85 , 86 , 87 , 89 , 93 , 101 , 103 , 109 , 110 ]. A variety of methods were employed by 29 studies to measure insulin sensitivity, namely the Matsuda index, insulin sensitivity index (ISI), quantitative insulin sensitivity check index (QUICKI) and the Cederholm index, and 20 (69.0%) signaled improvement [ 17 , 25 , 27 , 29 , 37 , 49 , 52 , 56 , 58 , 72 , 73 , 74 , 86 , 93 , 94 , 96 , 98 , 99 , 100 , 101 ].…”