Oxidative stress (OS) is defined as a disturbance in the prooxidant-antioxidant balance of the cell, in favor of the former, which results in the antioxidant capacity of the cell to be overpowered. Excess reactive oxygen species (ROS) production is very harmful to cell constituents, especially proteins, lipids, and DNA, thus causing damage to the cell. Oxidative stress has been associated with a variety of pathologic conditions, including diabetes mellitus (DM), cancer, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and accelerated aging. Regarding DM specifically, previous experimental and clinical studies have pointed to the fact that oxidative stress probably plays a major role in the pathogenesis and development of diabetic complications. It is postulated that hyperglycemia induces free radicals and impairs endogenous antioxidant defense systems through several different mechanisms. In particular, hyperglycemia promotes the creation of advanced glycation end-products (AGEs), the activation of protein kinase C (PKC), and the hyperactivity of hexosamine and sorbitol pathways, leading to the development of insulin resistance, impaired insulin secretion, and endothelial dysfunction, by inducing excessive ROS production and OS. Furthermore, glucose variability has been associated with OS as well, and recent evidence suggests that also hypoglycemia may be playing an important role in favoring diabetic vascular complications through OS, inflammation, prothrombotic events, and endothelial dysfunction. The association of these diabetic parameters (i.e., hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress will be reviewed here.

Diabetes mellitus is usually preceded by a pre-diabetic stage before the clinical presentation of the disease, the influence of which on persons’ quality of life is not adequately elucidated. The purpose of this study was to compare the Health-Related Quality of Life (HRQOL) of persons with pre-diabetes with that of diabetes or normal glucose tolerance (NGT), using the validated HRQOL-15D questionnaire. The HRQOL-15D scores of 172 people with pre-diabetes (108 with Impaired Fasting Glucose [IFG], 64 with Impaired Glucose Tolerance [IGT], aged 58.3 ± 10.3 years) and 198 with NGT (aged 54.4 ± 10.1 years) from the Greek part of the DEPLAN study (Diabetes in Europe - Prevention using Lifestyle, Physical Activity and Nutritional Intervention), were compared to 100 diabetes patients’ scores (aged 60.9 ± 12.5 years, diabetes duration 17.0 ± 10.0 years, HbA1c 7.2 ± 1.2%), derived from the outpatient Diabetes Clinic of a University Hospital. The diabetes patients’ HRQOL-15D score (0.8605) was significantly lower than the pre-diabetes’ (0.9008) and the controls’ (0.9092) (p < 0.001). There were no differences in the total score between the controls and the group with pre-diabetes. However, examination of individual parameters of the score showed that people with IGT had lower scores compared to the control group, as related to the parameters of “mobility” and “psychological distress”. No differences were found in any component of the HRQOL-15D score between the control group and the IFG group, nor between the two groups with pre-diabetes (IFG vs. IGT). Persons with pre-diabetes had a similar HRQOL score with healthy individuals, and a higher score than persons with diabetes. Specific components of the score, however, were lower in the IGT group compared to the controls. These findings help clarify the issue of HRQOL of persons with pre-diabetes and its possible impact on prevention.

Nanotechnology refers to the science that modulates molecules to the nanoscale dimension. Nanomedicine, i.e., the utilization of nanotechnology for diagnosing and treating several disorders, is a subject of ongoing research. The concept behind nanomedicine in diabetes mellitus (DM) treatment stems from the need to ameliorate absorption and distribution of antidiabetic therapies in order to overcome barriers, namely the pH throughout the gastrointestinal tract, the gut microbiota, the temperature/heat and the difficulties in the incorporation of drugs into the cells. Thus, the scope of nanomedicine is particularly challenging and demanding, considering the fact that the human body is a perpetually changing entity in order to achieve homeostasis. In this review, we will delve into various nanoparticles that are being studied in terms of antidiabetic treatment, their pros and cons and the expanding knowledge in this field. Despite the fact that nanomedicine seems to be very promising, there are still many gaps in our understanding of how the human body addresses its utilization. Moreover, its high costs, along with an as-yet unclear safety profile, remain a significant barrier to widespread adoption. In this review, we will describe both phytochemicals and chemical compounds that nanomedicine seeks to exploit in order to pave the way for a more efficacious and comprehensive management of diabetes mellitus.

Hypoglycemia has been associated with complications from the vasculature. The contributing effects of oxidative stress (OS) on these actions have not been sufficiently studied, especially in daily, routine clinical practice. We examined the association of hypoglycemia encountered in daily clinical practice with biomarkers of OS and endogenous antioxidant activity in persons with diabetes [type 1 (T1D) or type 2 (T2D)], as well as individuals without diabetes, with a history of hypoglycemia. Several biomarkers of OS (MDA, ADMA, ox-LDL, 3-NT, protein carbonyls, 4-HNE, TBARS) and antioxidant capacity (TAC, superoxide scavenging capacity, hydroxyl radical scavenging capacity, reducing power, ABTS) were measured. Blood was drawn at the time of hypoglycemia detection and under euglycemic conditions on a different day. A total of 31 participants (mean age [±SD] 52.2 ± 21.1 years, 45.2% males) were included in the study. There were 14 (45.2%) persons with T2D, 12 (38.7%) with T1D, and 5 (16.1%) without diabetes. We found no differences in the examined biomarkers. Only TBARS, a biomarker of lipid peroxidation, showed lower values during hypoglycemia (p = 0.005). This finding needs confirmation in more extensive studies, given that MDA, another biomarker of lipid peroxidation, was not affected. Our study suggests that hypoglycemia encountered in daily clinical practice does not affect OS.

Long-standing type 2 diabetes mellitus (DM) increases the risk of chronic coronary syndrome (CCS). We estimated the prevalence of undiagnosed CCS during routine outpatient care and described diagnostic testing strategies. This multicenter observational study was conducted in eight diabetes and cardiology outpatient clinics in Greece. Adults with DM ≥10 years and suspected ischemia [angina equivalents and/or ischemic electrocardiographic (ECG) abnormalities] without known CCS underwent joint diabetologist-cardiologist evaluation and appropriate non-invasive and/or invasive testing at physician discretion. Overall, 110 people with type 2 DM (mean age 65.4 years; 47.3% women; mean DM duration 21.3 years) were evaluated. CCS was diagnosed in 15 individuals (13.6%). No patient with CCS reported typical or atypical angina; presentations were mainly angina equivalents, most commonly fatigue (66.7%) and dyspnea (58.3%). Ischemic ECG abnormalities were present in 6/15 (40.0%), including repolarization or conduction changes. Initial tests varied: exercise ECG (33.6%), SPECT/PET (32.7%), and stress echocardiography (28.2%). This study highlights the diagnostic complexity of detecting CCS in individuals with type 2 DM, particularly due to the prevalence of non-classical symptoms. The findings underscore the importance of a personalized diagnostic approach and multidisciplinary collaboration between diabetologists and cardiologists, to improve cardiovascular risk stratification.