Recent reports have shown a strong association between obesity and the severity of COVID-19 infection, even in the absence of other comorbidities. After infecting the host cells, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a hyperinflammatory reaction through the excessive release of cytokines, a condition known as “cytokine storm,” while inducing lymphopenia and a disrupted immune response. Obesity is associated with chronic low-grade inflammation and immune dysregulation, but the exact mechanisms through which it exacerbates COVID-19 infection are not fully clarified. The production of increased amounts of cytokines such as TNFα, IL-1, IL-6, and monocyte chemoattractant protein (MCP-1) lead to oxidative stress and defective function of innate and adaptive immunity, whereas the activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome seems to play a crucial role in the pathogenesis of the infection. Endothelial dysfunction and arterial stiffness could favor the recently discovered infection of the endothelium by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic microenvironment in obesity could provide a link for the increased cardiovascular events in these patients. The successful use of anti-inflammatory agents such as IL-1 and IL-6 blockers in similar hyperinflammatory settings, like that of rheumatoid arthritis, has triggered the discussion of whether such agents could be administrated in selected patients with COVID-19 disease.

Diabetic Nephropathy (DN) is the commonest cause of end-stage renal failure (ESRF) in the Western world. Diabetic nephropathy follows a well outline clinical course, starting with microalbuminuria through proteinuria, azotaemia and culminating in ESRF. Before the onset of overt proteinuria, there are various renal functional changes including renal hyperfiltration, hyperperfusion, and increasing capillary permeability to macromolecules. Basement-membrane thickening and mesangial expansion have long been recognized as pathological hallmark of diabetes. It has been postulated that DN occurs as a result of the interplay of metabolic and hemodynamic factors in the renal microcirculation. There is no doubt that there is a positive relationship between hyperglycaemia, which is necessary but not sufficient, and microvascular complications. The accumulation of advanced glycosylated end-products (AGEs), the activation of isoform(s) of protein kinase C (PKC) and the acceleration of the aldose reductase pathway may explain how hyperglycemia damages tissue. PKC is one of the key signaling molecules in the induction of the vascular pathology of diabetes. The balance between extracellular matrix production and degradation is important in this context. Transforming growth factor-beta (TGF-beta) appears to play a pivotal role in accumulation in the diabetic kidney. Hemodynamic disturbances are believed to be directly responsible for the development of glomerulosclerosis and its attendant proteinuria. There is familial clustering of diabetic kidney disease. A number of gene loci have been investigated to try to explain the genetic susceptibility to diabetic nephropathy. The genes coding for components of renin-angiotensin system have drawn special attention, due to the central role that this system plays in the regulation of blood pressure, sodium metabolism, and renal hemodynamics. Endothelial dysfunction is closely associated with the development of diabetic retinopathy, nephropathy and atherosclerosis, both in IDDM and in NIDDM. The pathogenesis of diabetic nephropathy is not clarified completely yet.

Thyroid hormones have generally been found normal in diabetic patients. The question of whether variation within the euthyroid range influences insulin sensitivity in type 2 diabetes remains to be established. To investigate this, a meal was given to four groups: 17 healthy volunteers (controls), 22 first-degree relatives of type 2 diabetic subjects (relatives), 15 subjects with impaired glucose tolerance (IGT), and 24 subjects with overt type 2 diabetes (DM). Blood was drawn for 360 min for measurements of glucose and insulin. Plasma-free-T4(FT4) and plasma-free-T3(FT3) levels were measured. Fasting and postprandial insulin resistance was assessed by HOMA-IR and ISI indices, respectively. FT4 levels were found to be lower in controls (13.73 ± 0.48 pmol/l) than relatives, IGT, and DM (15.33 ± 0.52, 16.13 ± 0.65, and 17.7 ± 0.85 pmol/l, respectively, P = 0.007). FT3 levels were lower in controls (3.68 ± 0.09 pmol/l) than in relatives, IGT, and DM (4.35 ± 0.1, 4.8 ± 0.067, and 4.87 ± 0.11 pmol/l, respectively, P = 0.001). HOMA-IR was positively associated with FT4 and FT3 levels (β-co-efficient = 1.876 ± 0.476, P = 0.001; and 0.406 ± 0.090, P = 0.001, respectively). ISI was negatively associated with FT4 and FT3 levels (β-co-efficient = -0.051 ± 0.009, P = 0.001 and -0.009 ± 0.002, P = 0.001, respectively). In conclusion, increases of thyroid hormone levels within the normal range associate positively with insulin resistance. These data suggest that thyroid hormones may be part of the pathogenetic mechanism to explain metabolic derangement early in the development of type 2 diabetes.

No abstract

Chronic inflammation and increased oxidative stress are contributing factors to many non-communicable diseases. A growing body of evidence indicates that dietary nutrients can activate the immune system and may lead to the overproduction of pro-inflammatory cytokines. Fatty acids as macronutrients are key players for immunomodulation, with n-3 polyunsaturated fatty acids having the most beneficial effect, while polyphenols and carotenoids seem to be the most promising antioxidants. Psoriasis is a chronic, immune-mediated inflammatory disease with multifactorial etiology. Obesity is a major risk factor for psoriasis, which leads to worse clinical outcomes. Weight loss interventions and, generally, dietary regimens such as gluten-free and Mediterranean diet or supplement use may potentially improve psoriasis’ natural course and response to therapy. However, data about more sophisticated nutritional patterns, such as ketogenic, very low-carb or specific macro- and micro-nutrient substitution, are scarce. This review aims to present the effect of strictly structured dietary nutrients, that are known to affect glucose/lipid metabolism and insulin responses, on chronic inflammation and immunity, and to discuss the utility of nutritional regimens as possible therapeutic tools for psoriasis and psoriatic arthritis.

Objective: Although insulin resistance is a common finding in hyperthyroidism, the implicated mechanisms are obscure. The aim of this study was to investigate whether interleukin 6 (IL6) and tumour necrosis factor a (TNFa) are related to the development of insulin resistance in hyperthyroidism of nonautoimmune origin. Design and methods: A meal was given to ten hyperthyroid (HR) and ten euthyroid (EU) women. Plasma samples were taken for 360 min from the radial artery for measurements of glucose, insulin, and nonesterified fatty acids (NEFA). IL6 and TNFa were measured preprandially from the superficial epigastric vein and from the radial artery. Results: i) In HRversus EU: (a) arterial glucose was similar (AUC 0-360 2087G57 vs 2010G43 mM!min), but insulin was increased (AUC 0-360 17 267G2447 vs 10 331G666 mU/ml!min, PZ0.01), (b) homeostasis model assessment (HOMA) was increased (2.3G0.4 vs 1G0.1 kg/m 2 , PZ0.007), (c) arterial NEFA were increased (AUC 0-360 136G18 vs 89G7 mmol/l!min, PZ0.03), (d) arterial IL6 (2G0.3 vs 0.9G0.1 pg/ml, PZ0.0009) and TNFa (4.2G0.8 vs 1.5G0.2 pg/ml, PZ0.003) were increased, and (e) IL6 production from the subcutaneous adipose tissue (AT) was increased (18G6 vs 5G1 pg/min per 100 ml tissue, PZ0.04). ii) (a) Subcutaneous venous IL6 was positively associated with HOMA (b-coefficientZ1.7G0.7, PZ0.049) and (b) although TNFa was not produced by the subcutaneous AT, arterial TNFa was positively associated with NEFA (AUC 0-360 ; b-coefficientZ0.045G0.01, PZ0.005). Conclusions: In hyperthyroidism: i) glucose and lipid metabolism are resistant to insulin, ii) subcutaneous AT releases IL6, which could then act as an endocrine mediator of insulin resistance, iii) although there is no net secretion of TNFa by the subcutaneous AT, increased systemic TNFa levels may be related to the development of insulin resistance in lipolysis.

Background: Anaemia is a common finding in diabetes, particularly in those patients with albuminuria or renal dysfunction and is associated with impaired erythropoietin (EPO) secretion. This review focuses on mechanisms involved in the regulation of erythropoiesis in diabetic patients in an effort to elucidate the competing effects of the renin angiotensin system (RAS) blockade and sodium-glucose cotransporter-2 (SGLT2) inhibitors on haemoglobin concentration and hematocrit values. Summary: The RAS shows significant activation in diabetic subjects. Angiotensin II, its active octapeptide, causes renal tubulointerstitial hypoxia, which stimulates hypoxia-inducible factors (HIF) and increases EPO secretion and erythropoiesis. As expected, drugs that inactivate RAS, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB) are associated with a significant hematocrit-lowering effect and/or anaemia in various clinical conditions, including diabetes. Dual blockade by a combination of ACEi and ARB in diabetic patients achieves a better RAS inhibition, but at the same time a worse drop of haemoglobin concentration. Increased glucose reabsorption by SGLTs in diabetic subjects generates a high-glucose environment in renal tubulointerstitium, which may impair HIF-1, damage renal erythropoietin-producing cells (REPs) and decrease EPO secretion and erythropoiesis. SGLT2 inhibitors, which inhibit glucose reabsorption, may attenuate glucotoxicity in renal tubulointerstitium, allowing REPs to resume their function and increase EPO secretion. Indeed, EPO levels increase within a few weeks after initiation of therapy with all known SGLT2 inhibitors, followed by increased reticulocyte count and a gradual elevation of haemoglobin concentration and hematocrit level, which reach zenith values after 2-3 months. Key Messages: The competing effects of RAS blockade and SGLT2 inhibitors on erythropoiesis may have important clinical implications. The rise of hematocrit values by SGLT2 inhibitors given on top of RAS blockade in recent outcome trials may significantly contribute to the cardiorenal protection attained. The relative contribution of each system to erythropoiesis and outcome remains to be revealed in future studies.

Aliskiren had a favorable effect on endothelial function and EPCs, reduced arterial stiffness, and improved LV twisting and untwisting. These effects were independent of BBP lowering, as they were not observed after the achievement of similar values of BBP with HCTZ.