Oxidative stress and hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of diabetic cardiovascular and renal diseases. Reactive oxygen species (ROS) mediate physiological and pathophysiological processes, being involved in the modulation of cell signaling, differentiation, and survival, but also in cyto- and genotoxic damage. As master regulators of glycolytic metabolism and oxygen homeostasis, HIFs have been largely studied for their role in cell survival in hypoxic conditions. However, in addition to hypoxia, other stimuli can regulate HIFs stability and transcriptional activity, even in normoxic conditions. Among these, a regulatory role of ROS and their byproducts on HIFs, particularly the HIF-1α isoform, has received growing attention in recent years. On the other hand, HIF-1α and HIF-2α exert mutually antagonistic effects on oxidative damage. In diabetes, redox-mediated HIF-1α deregulation contributes to the onset and progression of cardiovascular and renal complications, and recent findings suggest that deranged HIF signaling induced by hyperglycemia and other cellular stressors associated with metabolic disorders may cause mitochondrial dysfunction, oxidative stress, and inflammation. Understanding the mechanisms of mutual regulation between HIFs and redox factors and the specific contribution of the two main isoforms of HIF-α is fundamental to identify new therapeutic targets for vascular complications of diabetes.

The adipose organ adapts and responds to internal and environmental stimuli by remodeling both its cellular and extracellular components. Under conditions of energy surplus, the subcutaneous white adipose tissue (WAT) is capable of expanding through the enlargement of existing adipocytes (hypertrophy), followed by de novo adipogenesis (hyperplasia), which is impaired in hypertrophic obesity. However, an impaired hyperplastic response may result from various defects in adipogenesis, leading to different WAT features and metabolic consequences, as discussed here by reviewing the results of the studies in animal models with either overexpression or knockdown of the main molecular regulators of the two steps of the adipogenesis process. Moreover, impaired WAT remodeling with aging has been associated with various age-related conditions and reduced lifespan expectancy. Here, we delve into the latest advancements in comprehending the molecular and cellular processes underlying age-related changes in WAT function, their involvement in common aging pathologies, and their potential as therapeutic targets to influence both the health of elderly people and longevity. Overall, this review aims to encourage research on the mechanisms of WAT maladaptation common to conditions of both excessive and insufficient fat tissue. The goal is to devise adipocyte-targeted therapies that are effective against both obesity- and age-related disorders.

Carbonyl stress is a condition characterized by an increase in the steady-state levels of reactive carbonyl species (RCS) that leads to accumulation of their irreversible covalent adducts with biological molecules. RCS are generated by the oxidative cleavage and cellular metabolism of lipids and sugars. In addition to causing damage directly, the RCS adducts, advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), cause additional harm by eliciting chronic inflammation through receptor-mediated mechanisms. Hyperglycemia- and dyslipidemia-induced carbonyl stress plays a role in diabetic cardiovascular complications and diabetes-related cancer risk. Moreover, the increased dietary exposure to AGEs/ALEs could mediate the impact of the modern, highly processed diet on cardiometabolic and cancer risk. Finally, the transient carbonyl stress resulting from supraphysiological postprandial spikes in blood glucose and lipid levels may play a role in acute proinflammatory and proatherogenic changes occurring after a calorie dense meal. These findings underline the potential importance of carbonyl stress as a mediator of the cardiometabolic and cancer risk linked to today’s unhealthy diet. In this review, current knowledge in this field is discussed along with future research courses to offer new insights and open new avenues for therapeutic interventions to prevent diet-associated cardiometabolic disorders and cancer.

Background: Psychological well-being and quality of life (QoL) are important outcomes of lifestyle interventions, as a positive impact may favour long-term maintenance of behaviour change. Objective: This study investigated the effect of a behavioural intervention for adopting and maintaining an active lifestyle on psychological well-being and health-related QoL in individuals with type 2 diabetes. Methods: Three hundred physically inactive and sedentary patients were randomized 1:1 to receive 1 month’s theoretical and practical counselling once a year (intervention group, INT) or standard care (control group, CON) for 3 years. Psychological well-being and QoL, assessed using the World Health Organization (WHO)-5 and the 36-Item Short Form (SF-36) questionnaire, respectively, were pre-specified secondary endpoints. The primary endpoint was sustained behaviour change, as assessed by accelerometer-based measurement of physical activity (PA) and sedentary time. Results: WHO-5 and SF-36 physical and mental component summary (PCS and MCS) scores increased progressively in the INT group and decreased in the CON group, resulting in significant between-group differences (WHO-5: mean difference 7.35 (95% confidence interval (CI) 3.15–11.55), P = 0.0007; PCS 4.20 (95% CI 2.25–6.15), P < 0.0001; MCS 3.04 (95% CI 1.09–4.99), P = 0.0025). Percentage of participants with likely depression decreased in the INT group and increased in the CON group. PA volume changes were independently associated with WHO-5 changes, which were significantly higher in participants who accumulated > 150 min·wk⁻¹ of moderate-to-vigorous intensity PA versus those who did not (13.06 (95% CI 7.51–18.61), P < 0.0001), whereas no relationship was detected for QoL. Conclusion: A counselling intervention that was effective in promoting a sustained change in PA and sedentary behaviour significantly improved psychological well-being and QoL. Trial Registration: ClinicalTrials.gov; NCT01600937; 10 October 2012.

Introduction Type 2 diabetes (T2D) is associated with an increased fracture risk despite normal-to-increased bone mineral density, suggesting reduced bone quality. Exercise may be effective in reducing fracture risk by ameliorating muscle dysfunction and reducing risk of fall, though it is unclear whether it can improve bone quality. Methods and analysis The ‘Study to Weigh the Effect of Exercise Training on BONE quality and strength (SWEET BONE) in T2D’ is an open-label, assessor-blinded, randomised clinical trial comparing an exercise training programme of 2-year duration, specifically designed for improving bone quality and strength, with standard care in T2D individuals. Two hundred T2D patients aged 65–75 years will be randomised 1:1 to supervised exercise training or standard care, stratified by gender, age ≤ or >70 years and non-insulin or insulin treatment. The intervention consists of two weekly supervised sessions, each starting with 5 min of warm-up, followed by 20 min of aerobic training, 30 min of resistance training and 20 min of core stability, balance and flexibility training. Participants will wear weighted vests during aerobic and resistance training. The primary endpoint is baseline to end-of-study change in trabecular bone score, a parameter of bone quality consistently shown to be reduced in T2D. Secondary endpoints include changes in other potential measures of bone quality, as assessed by quantitative ultrasound and peripheral quantitative CT; bone mass; markers of bone turnover; muscle strength, mass and power; balance and gait. Falls and asymptomatic and symptomatic fractures will be evaluated over 7 years, including a 5-year post-trial follow-up. The superiority of the intervention will be assessed by comparing between-groups baseline to end-of-study changes. Ethics and dissemination This study was approved by the institutional ethics committee. Written informed consent will be obtained from all participants. The study results will be submitted for peer-reviewed publication. Trial registration number NCT02421393; Pre-results.