Background—Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F₂-isoprostane 8-iso-prostaglandin (PG)F_2α, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation.Methods and Results—Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF_2αand 11-dehydro-thromboxane B₂(TXM), an in vivo index of platelet activation. Sixty-two had non–insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF_2αin this setting. Urinary 8-iso-PGF_2αexcretion was significantly higher (P=0.0001) in NIDDM patients (419±208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208±92; 41 to 433). Urinary 8-iso-PGF_2αwas linearly correlated with blood glucose and urinary TXM. 8-iso-PGF_2αexcretion was also significantly (P=0.0001) higher in IDDM patients (400±146; 183 to 702) than in control subjects (197±69; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF_2α(by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P=0.0001) reduction in 8-iso-PGF_2αand TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF_2αwas unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion.Conclusions—We conclude that DM is associated with increased formation of F₂-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.

Gestational Diabetes Mellitus (GDM) is the most common metabolic condition during pregnancy and may result in short- and long-term complications for both mother and offspring. The complexity of phenotypic outcomes seems influenced by genetic susceptibility, nutrient-gene interactions and lifestyle interacting with clinical factors. There is strong evidence that not only the adverse genetic background but also the epigenetic modifications in response to nutritional and environmental factors could influence the maternal hyperglycemia in pregnancy and the foetal metabolic programming. In this view, the correlation between epigenetic modifications and their transgenerational effects represents a very interesting field of study. The present review gives insight into the role of gene variants and their interactions with nutrients in GDM. In addition, we provide an overview of the epigenetic changes and their role in the maternal-foetal transmission of chronic diseases. Overall, the knowledge of epigenetic modifications induced by an adverse intrauterine and perinatal environment could shed light on the potential pathophysiological mechanisms of long-term disease development in the offspring and provide useful tools for their prevention.

The human circadian system has a period of approximately 24 h and studies on the consequences of “chornodisruption” have greatly expanded. Lifestyle and environmental factors of modern societies (i.e., artificial lighting, jetlag, shift work, and around-the-clock access to energy-dense food) can induce disruptions of the circadian system and thereby adversely affect individual health. Growing evidence demonstrates a complex reciprocal relationship between metabolism and the circadian system, in which perturbations in one system affect the other one. From a nutritional genomics perspective, genetic variants in clock genes can both influence metabolic health and modify the individual response to diet. Moreover, an interplay between the circadian rhythm, gut microbiome, and epigenome has been demonstrated, with the diet in turn able to modulate this complex link suggesting a remarkable plasticity of the underlying mechanisms. In this view, the study of the impact of the timing of eating by matching elements from nutritional research with chrono-biology, that is, chrono-nutrition, could have significant implications for personalized nutrition in terms of reducing the prevalence and burden of chronic diseases. This review provides an overview of the current evidence on the interactions between the circadian system and nutrition, highlighting how this link could in turn influence the epigenome and microbiome. In addition, possible nutritional strategies to manage circadian-aligned feeding are suggested.