Diabetes is a complex, heterogeneous condition that has beta cell dysfunction at its core. Many factors (e.g. hyperglycemia/glucotoxicity, lipotoxicity, autoimmunity, inflammation, adipokines, islet amyloid, incretins and insulin resistance) influence the function of pancreatic beta cells. Chronic hyperglycaemia may result in detrimental effects on insulin synthesis/secretion, cell survival and insulin sensitivity through multiple mechanisms: gradual loss of insulin gene expression and other beta-cell specific genes; chronic endoplasmic reticulum stress and oxidative stress; changes in mitochondrial number, morphology and function; disruption in calcium homeostasis. In the presence of hyperglycaemia, prolonged exposure to increased free fatty acids result in accumulation of toxic metabolites in the cells (“lipotoxicity”), finally causing decreased insulin gene expression and impairment of insulin secretion. The rest of the factors/mechanisms which impact on the course of the disease are also discusses in detail.

The complex pathological mechanisms responsible for development of type 2 diabetes are not fully addressed by conventional drugs, which are also associated with inconvenient side effects such as weight gain or hypoglycemia. Two types of incretin-based therapies are now in use: incretin mimetics (glucagon-like peptide-1 [GLP-1] receptor agonists that bind specific receptors and mimic the action of natural GLP-1) and incretin enhancers (inhibitors of the enzyme that degrade the incretin hormones and thus prolong their activity). Both offer important advantages over previous agents. In addition to the proven glucose-lowering efficacy, they promote weight loss (or are weight neutral) by slowing gastric emptying and inducing satiety, inhibit glucagon secretion with maintenance of counterregulatory mechanisms, and exhibit cardiovascular benefits, while having a low risk profile. Importantly, short-term studies have shown that incretins/incretin-based therapies protect β-cells (by enhancing cell proliferation and differentiation and inhibiting apoptosis) and stimulate their function (by recruiting β-cells to the secretory process and increasing insulin biosynthesis/secretion). These therapies have the opportunity to interfere with the disease progression if used as an early intervention, when enough β-cell mass/function can still be preserved or restored.

COVID-19 is currently considered an inflammatory disease affecting the entire organism. In severe forms, an augmented inflammatory response leads to the fulminant “cytokine storm”, which may result in severe multisystemic end-organ damage. Apart from the acute inflammatory response, it seems that chronic inflammation also plays a major role in the clinical evolution of COVID-19 patients. Pre-existing inflammatory conditions, such as those associated with chronic coronary diseases, type 2 diabetes mellitus or obesity, may be associated with worse clinical outcomes in the context of COVID-19 disease. These comorbidities are reported as powerful predictors of poor outcomes and death following COVID-19 disease. Moreover, in the context of chronic coronary syndrome, the cytokine storm triggered by SARS-CoV-2 infection may favor vulnerabilization and rupture of a silent atheromatous plaque, with consequent acute coronary syndrome, leading to a sudden deterioration of the clinical condition of the patient. This review aims to present the current status of knowledge regarding the link between COVID-19 mortality, systemic inflammation and several major diseases associated with poor outcomes, such as cardiovascular diseases, diabetes and obesity.

In the pathogenesis of type 2 diabetes mellitus (T2DM), diet plays a key role. Individualized medical nutritional therapy, as part of lifestyle optimization, is one of the cornerstones for the management of T2DM and has been shown to improve metabolic outcomes. This paper discusses major aspects of the nutritional intervention (including macro- and micronutrients, nutraceuticals, and supplements), with key practical advice. Various eating patterns, such as the Mediterranean-style, low-carbohydrate, vegetarian or plant-based diets, as well as healthy eating plans with caloric deficits have been proven to have beneficial effects for patients with T2DM. So far, the evidence does not support a specific macronutrient distribution and meal plans should be individualized. Reducing the overall carbohydrate intake and replacing high glycemic index (GI) foods with low GI foods have been shown as valid options for patients with T2DM to improve glycemic control. Additionally, evidence supports the current recommendation to reduce the intake of free sugars to less than 10% of total energy intake, since their excessive intake promotes weight gain. The quality of fats seems to be rather important and the substitution of saturated and trans fatty acids with foods rich in monounsaturated and polyunsaturated fats lowers cardiovascular risk and improves glucose metabolism. There is no benefit of supplementation with antioxidants, such as carotene, vitamins E and C, or other micronutrients, due to the lack of consistent evidence showing efficacy and long-term safety. Some studies suggest possible beneficial metabolic effects of nutraceuticals in patients with T2DM, but more evidence about their efficacy and safety is still needed.