**6. Blood glucose and lipid status in psoriasis patients during treatment with heliotherapy**

Psoriasis is considered a chronic and debilitating inflammatory disease associated with serious comorbidities (124, 125). Large epidemiological studies have shown that psoriasis and psoriatic arthritis are associated with metabolic diseases including obesity, dyslipidemia and diabetes(126). The chronic inflammation in psoriasis can predispose patients to other inflammatory conditions. The proinflammatory cytokines, such as tumor necrosis factor- (TNF-), and other factors that are overproduced in patients with psoriasis likely contribute to the increased risk for the development of metabolic syndrome(127, 128).

Inflammatory factors have also been associated with insulin resistance and β-cell failure, both of which are key features of type 2 diabetes mellitus (129). There is evidence that vitamin D may stimulate pancreatic insulin secretion directly through nuclear receptors that are found in a wide variety of tissues, including T and B lymphocytes, skeletal muscle, and the pancreatic islet β-cells(130). There is some evidence that suggests increased PTH activity is associated with, and possibly causes, reduced insulin sensitivity(130). The prevalence of impaired glucose tolerance and diabetes mellitus is increased in patients with primary hyperparathyroidism (131, 132).

Vitamin D has a wide range of effects on the immune system: it promotes the differentiation of monocytes into macrophages thus increasing their cytotoxic activity; reduces the antigenpresenting activity of macrophages to lymphocytes; prevents dendritic cell maturation; inhibits T lymphocyte-mediated immunoglobulin synthesis in B cells and inhibits delayedtype hypersensitivity reactions(8, 133, 134). Furthermore vitamin D has been reported to down-regulate the production of several cytokines: IL-2, IL-6 and IL-12, interferon-γ, TNF-α, and TNF-β (134, 135). Alternations in vitamin D status and/or action may affect insulin sensitivity, β-cell function or both. Therefore, vitamin D may be involved in the pathogenesis of type 2 diabetes mellitus at both environmental and genetic levels(129). Psoriasis patients are more likely to be insulin resistant and to have impaired glucose tolerance, higher fasting insulin levels, and impaired β-cell function than non-psoriatic subjects(136).

Heliotherapy improves lipid and carbohydrate status of psoriasis patients(56). Increases in high-density lipoprotein (HDL)-cholesterol and decreases in HbA1c during climate therapy could be explained by several factors. One possible mechanism could be a direct effect of vitamin D on insulin sensitivity(130). Another is that sun exposure usually implies greater outdoor physical activity, leading to beneficial effects on lipids and insulin sensitivity,

UVB and Vitamin D in Psoriasis 133

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**8. References** 

unrelated to serum 25(OH)D concentrations(130). Diet might also influence glucose and lipid metabolism. Although climate therapy did not change the basal glucose levels of the patients, the HbA1c levels decreased about 10 %, indicating improved insulin sensitivity (56). The observed associations between vitamin D, insulin, and glucose metabolism in humans have not yet been confirmed by intervention studies and, hence, a causal association has not been established(130).

A high prevalence of atherosclerosis is also reported in psoriasis patients. High serum lipid levels have been suggested in the pathogenesis of atherosclerosis. High serum lipid levels are more common in psoriasis and may be responsible for an elevated prevalence of cardiovascular accidents in this group of patients(137). Patients with psoriasis exhibit a dyslipidemic profile, including increased levels of plasma cholesterol, triglycerides (TG), LDL, very low-density lipoprotein (VLDL) cholesterol and decreased levels of HDL cholesterol. Lipid abnormalities in psoriasis patients may be genetically determined(138). The ratio of low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) decreased, and the levels of hemoglobin A1c (HbA1c) also decreased in psoriasis patients during heliotherapy(56). Serum concentrations of 25(OH)D at baseline in psoriasis patients treated with heliotherapy correlated positively with serum HDL at baseline(56), consistent with a previously published study(139).

Psoriasis is associated with obesity, which is a component of metabolic syndrome. Obesity has been shown to be an independent risk factor for the development of psoriasis, and is also associated with more severe psoriasis (140). Abdominal obesity is a proinflammatory state with the visceral adipose tissue providing a rich source of inflammatory molecules known as adipocytokines including leptin, adiponectin, visfatin and resistin. This may explain an important association between obesity, insulin resistance and related inflammatory disorders.

Inflammation plays a key role in the pathogenesis of psoriasis and a number of chronic inflammatory systemic diseases listed above. Activated inflammatory cells and proinflammatory cytokines, such as TNF-α and IL-1β, contribute to the development of psoriatic lesions and play an important role in atherosclerosis (141).
