diabetes mellitus type 2 | Acta Medica Marisiensis

Utilization of lipoxins and other specialised pro-resolving mediators in the prevention and treatment of diabetic nephropathy and diabetic cardiovascular disease

Ivan Bergo¹, Ylenia Pastorello²

1. Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science and Technology, Campus Hamburg, Hamburg, Germany
2. Department of Anatomy and Embryology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mureș, Romania

DOI: 10.2478/amma-2024-0037

Diabetes mellitus type 2 is a chronic disease caused by insulin resistance. Whilst first originating in the adipose tissue, this pathophysiological process later affects the muscles and the liver as well. This induces high plasma levels of glucose and fatty acids, leading to the inflammatory-related chronic complications of diabetes, such as diabetic nephropathy and diabetic cardiovascular disease. Specialized pro-resolving mediators are lipid mediators responsible for resolving inflammation and could therefore be beneficial in the management of chronic diabetes complications. The aim of this review is to assess if specialised pro-resolving mediators have the potential to attenuate the chronic complications of diabetes. Specialised pro-resolving mediators, especially lipoxins, can modulate both diabetic nephropathy and diabetic cardiovascular disease. In mice it was demonstrated that, at the glomerular level, lipoxins reduced collagen deposition and expression of pro-inflammatory markers. In human saphenous vein smooth muscle cells instead, lipoxins were able to reduce collagen deposition and vascular smooth muscle cells proliferation and chemotaxis. Aspirin is a medication that could be used to modulate specialised pro-resolving mediator levels, as aspirin triggered-specialised pro-resolving mediators exist. Aspirin triggered-specialised pro-resolving mediators are pro-resolving substances with similar effects, but synthetised in a different way, requiring the partial blockage of the cyclooxygenase 2 enzyme. These results demonstrate how such substances could be useful in the treatment of diabetic patients and why further research is needed to create efficient and economical medications.

Background: Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Systemic inflammation can initiate or worsen comorbid diseases, such as ischemic heart disease, heart failure, arrhythmia, diabetes, osteoporosis, lung cancer and depression.
Material and method: We explored the Medprax database, from an ambulatory care in order to obtain rates of comorbidities in COPD patients. Medprax electronic database is a locally developed system designed to fulfil the requirements of an integrated healthcare system. We identified a population of 9,659 patients (4472 men and 5187 women) aged ≥ 30 years registered between 01.01.2000 and 01.02.2010.
Results: The overall prevalence of COPD was 5.17% (384 men and 116 women). Compared to the non-COPD patients, COPD was found to be a significant risk factor in both sexes for cardiovascular events: ischemic heart disease (OR = 3.06, 95%CI 2.54–3.68), atrial fibrillation (OR = 2.70, 95%CI 2.12–3.43) and heart failure (OR = 4.49, 95%CI 3.74–5.40) regardless of age. Association with diabetes mellitus type 2 was extremely significant in COPD men (OR = 1.69, 95%CI 1.26–2.27), but not in COPD women. Significant correlation with osteoporosis (OR = 3.26, 95%CI 1.94–5.48) was found only in women over 60 years and men under 60. Pulmonary malignancy was found only in male COPD patient compared to non-COPD patients (OR = 5.04, 95%CI 2.02–12.44). The impact on
depressive disorders was noted only in younger COPD men (OR = 5.71, 95%CI 1.94–16.82).
Conclusions: Our results indicate that COPD is a risk factor for all these comorbid conditions and that in the management of COPD all these conditions need to be carefully evaluated.