PSORIASIS AND DIABETES: A PERILOUS COMBINATION. A PREVALENCE STUDY EVALUATING THE ROLE OF INSULIN-RESISTANCE, CARDIOVASCULAR RISK BIOMARKERS, LIPIDIC PROFILE AND DETRIMENTAL LIFE-STYLE IN PSORIATIC PATIENTS WITH AND WITHOUT T2DM

Abstract: Introduction: Psoriasis is a chronic dermatosis with a high prevalence in the general population (between 0.5% and 4.6%), characterized by a multifactorial pathogenesis with an important genetic component. The main clinical feature of psoriasis is the erythematous-desquamative plaque, even though the lesions may presents in different forms. Numerous studies have highlighted how the psoriatic patients are often burdened by a wide array of different co-morbidities, which negatively impact their quality of life and complicate the therapeutic approach. In particular, psoriatics patients are subjected to increased cardio-metabolic risk factors, such as obesity, T2DM, hypertriglyceridemia and hypertension, but also to detrimental lifestyles like the consumption of alcohol and tobacco. Therefore Psoriasis should be considered as a systemic pathology with important consequence in terms of risk for cardio-metabolic diseases. In particular the typical inflammatory state of psoriasis and an unhealthy lifestyle are independently associated with obesity, insulin resistance and an unfavorable cardiovascular risk profile. This is mainly explained by the fact that inflammation results in an activation of T-helper 1 lymphocytes, with a consequent release of inflammatory cytokines such as C-reactive protein and tumor necrosis factor -α (TNFα) and an increased platelet activation that plays a major role in atherogenesis. Type II diabetes mellitus, although certainly related to obesity, has been shown to have a close link with Psoriasis independently of obesity. Prevalence studies of diabetes mellitus II show that it increases based on the age and severity of Psoriasis (PASI) and duration of psoriatic disease itself: the fundamental pathogenetic link could be attributable to the increase in TNFα, endowed with hyperglycemic properties, given its anti-insulin action on adipocytes and hepatocytes. Objective: This study aims to evaluate the lipidic profile, insulin-resistance, and cardiovascular risk profile of psoriatics patients with or without co-morbid T2DM. Methods: A total of 425 patients were enrolled, of which: 86 psoriatics, 69 psoriatic with T2DM, 120 T2DM patients and 150 controls. The Psoriasis Area and Severity Index (PASI), body mass index (BMI), insuline resistance parameters (evaluated with the HOMA-IR) were assessed in these patients, along with an evaluation of the lipidic profile, plasminogen activator inhibitor-1 (PAI-1), homocysteine, soluble adhesion molecules, MMPs and adipocytokines concentrations. Results: showed higher levels of FPG, HbA 1c and HOMA-IR in diabetics with psoriasis (p<0.0001) than psoriatics. FPI levels resulted increased in diabetics with psoriasis than diabetics and psoriatics (p<0.0001), as well as increased in psoriatic with respect to controls (p<0.0001). LDL-C levels and homocysteine concentrations resulted higher in psoriatics and diabetics with psoriasis (p<0.0001) than diabetics. PAI-1 levels resulted higher in diabetics with psoriasis when compared to diabetics (p<0.01). sICAM-1 and sVCAM-1 concentration resulted increased in diabetics with psoriasis when compared to diabetics (p<0.001 and p<0.01) and psoriatics (p<0.001 and p<0.0001). Visfatin and resistin levels showed a reduction in their plasmatic concentrations in psoriatics (p<0.0001) and in diabetics with psoriasis (p<0.001 and p<0.0001) when compared to diabetics. Conclusions: This study underlines the close relationship between psoriasis and diabetes. Insulin-resistance appears to be the pathological link intertwining psoriasis with its related comorbidities. As a result psoriasis appears to increase the cardio-metabolic risk in diabetics patients. Therefore, considering psoriasis as a systemic disease to all extent and taking into account the underlying chronic inflammation, aberrant immune-activation and metabolic implications, could lead to a major improve in the management of these patients.