Glucose metabolism in patients with psoriasis.

BACKGROUND: Epidemiological studies strongly suggest that psoriasis predisposes to type 2 diabetes. Several theories have been proposed to explain how these disease entities might be pathophysiologically connected. OBJECTIVES: Our primary objective was to elucidate whether clinical data support the notion of common pathophysiological denominators in patients with psoriasis and type 2 diabetes, and thus to delineate the association between the two conditions that has arisen on the basis of epidemiological studies. METHODS: We reviewed clinical studies investigating parameters of glucose metabolism in patients with psoriasis. The PubMed and Embase databases were searched for studies investigating glucose metabolism in adult patients with psoriasis as a primary or secondary end point. Studies had to include a relevant control group. RESULTS: Twenty-six clinical studies reporting on insulin resistance, glucose tolerance or insulin secretion were eligible for review. The results were widely conflicting, with less than half of the studies showing results suggestive of defective glucose metabolism in patients with psoriasis. In general, the studies suffered from a lack of information regarding possible confounders and patient characteristics. Furthermore, the research methods varied, and in all but one study they might not have been appropriate to detect early and subtle defects in glucose metabolism. CONCLUSIONS: The available literature does not unequivocally support common pathophysiological denominators in psoriasis and type 2 diabetes. Well-designed clinical studies are needed to expose potential diabetogenic defects in the glucose metabolism in patients with psoriasis.

Impaired incretin effect is an early sign of glucose dysmetabolism in nondiabetic patients with psoriasis.

BACKGROUND: Patients with psoriasis have an increased risk of type 2 diabetes. The gastrointestinal system plays a major role in normal glucose metabolism, and in healthy individuals, postprandial insulin secretion is largely mediated by the gut incretin hormones. This potentiation is termed the incretin effect and is reduced in type 2 diabetes. The impact of psoriasis on gastrointestinal factors involved in glucose metabolism has not previously been examined. OBJECTIVE: To investigate whether the incretin effect, gastrointestinal-mediated glucose disposal (GIGD) and/or secretion of glucagon and gut incretin hormones are impaired in normal glucose-tolerant patients with psoriasis. METHODS: Oral glucose tolerance tests and intravenous isoglycaemic glucose infusions were performed in 12 patients with moderate-to-severe psoriasis and 12 healthy matched control subjects. RESULTS: In patients with psoriasis, the incretin effect (39% vs. 57%, P = 0.02) and GIGD (53% vs. 61%, P = 0.04) were significantly reduced compared to control subjects. In addition, patients were glucose intolerant and showed exaggerated glucose-dependent insulinotropic polypeptide responses. CONCLUSION: These novel findings support the notion that psoriasis is a prediabetic condition and suggest that gastrointestinal-related mechanisms are involved in the increased susceptibility to type 2 diabetes in patients with psoriasis.

Lack of effect of the glucagon-like peptide-1 receptor agonist liraglutide on psoriasis in glucose-tolerant patients--a randomized placebo-controlled trial.

BACKGROUND: It has been proposed that glucagon-like peptide-1 receptor (GLP-1R) agonists used for the treatment of patients with type 2 diabetes might also improve their psoriasis. OBJECTIVE: To assess the efficacy and safety of the GLP-1R agonist liraglutide in glucose-tolerant patients with plaque psoriasis. METHODS: A total of 20 obese (body mass index > 25 kg/m(2)), glucose-tolerant patients with plaque psoriasis (psoriasis area and severity index (PASI) of at least 8) were randomized 1:1 to once-daily subcutaneous injections with liraglutide or placebo for an 8-week period. The primary end points were improvement in PASI and dermatology life quality index (DLQI). Secondary end points included changes in weight and high sensitive C-reactive protein (hsCRP) levels, as well as adverse events. RESULTS: After 8 weeks of treatment, no significant change in PASI was found in the liraglutide group (mean±standard deviation: -2.6 ± 2.1) compared with the placebo group (-1.3 ± 2.4) (P = 0.228). No difference in DLQI was observed between the groups [-2.5 ± 4.4 (liraglutide) vs. -3.7 ± 4.8 (placebo); P = 0.564]. HsCRP did not change in any of the groups (0.26 ± 1 (placebo) vs. 0.25 ± 2.2 (liraglutide); P = 0.992). Liraglutide treatment resulted in a bodyweight loss of 4.7 ± 2.5 kg compared with 1.6 ± 2.7 kg in the placebo group (P = 0.014) accompanied by decreased cholesterol levels. No serious adverse events occurred during the 8-week observation period. The most common complaint was transient nausea, which occurred in 45% of the liraglutide-treated patients but in none from the placebo group. CONCLUSION: Liraglutide treatment for 8 weeks did not significantly change PASI, DLQI, or hsCRP in a small group of glucose-tolerant obese patients with plaque psoriasis compared with placebo. A significant weight loss and decrease in cholesterol levels was observed in liraglutide-treated patients.

'Short-term treatment with methotrexate does not affect microvascular endothelial function in patients with psoriasis'.

BACKGROUND: Psoriasis is associated with increased risk of cardiovascular disease (CVD), possibly due to chronic low-grade systemic inflammation. Systemic anti-inflammatory treatment might reduce the risk of CVD. OBJECTIVE: Our aim was to investigate if short-term treatment with methotrexate influences microvascular endothelial function (MEF), an early surrogate marker of atherosclerosis, in patients with psoriasis. METHODS: We prospectively studied a hospital cohort of patients with psoriasis. Measurements of MEF were performed with the Endo-PAT2000© device at baseline and after 8-10 weeks of treatment with methotrexate. At the same time points, we recorded anamnestic information, measured body mass index (BMI), waist and hip circumferences and blood pressure, and drew blood samples (lipid profile, HbA1 and hs-CRP). Psoriasis severity was evaluated by psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI). RESULTS: A total of 32 patients with psoriasis were included. Median age was 46 (range 18-82) years, and 50% were men. Twenty-seven patients completed the study. After 8-10 weeks, median PASI had decreased significantly by 6.2 (from 9.8 to 3.6), and DLQI had decreased by 7 (from 9 to 2). No significant changes were observed in MEF, expressed by reactive hyperaemia index and augmentation index. Also, we saw no significant changes in BMI, waist-hip ratio, blood pressure and blood samples. CONCLUSION: Short-term treatment with methotrexate did not affect MEF in patients with psoriasis. Further studies are warranted.

Correlation between human papillomavirus and p16 overexpression in oropharyngeal tumours: a systematic review.

BACKGROUND: A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based on diagnostic measures and definition of p16 overexpression. We evaluated means of p16 and HPV diagnostics, and quantified overexpression of p16 in HPV-positive and -negative OP-SCCs by mode of immunohistochemical staining of carcinoma cells. METHODS: PubMed, Embase, and the Cochrane Library were searched from 1980 until October 2012. We applied the following inclusion criteria: a minimum of 20 cases of site-specific OP-SCCs, and HPV and p16 results present. Studies were categorised into three groups based on their definition of p16 overexpression: verbal definition, nuclear and cytoplasmatic staining between 5 and 69%, and ≥70% staining. RESULTS: We identified 39 studies with available outcome data (n=3926): 22 studies (n=1980) used PCR, 6 studies (n=688) used ISH, and 11 studies (n=1258) used both PCR and ISH for HPV diagnostics. The methods showed similar HPV-positive results. Overall, 52.5% of the cases (n=2062) were HPV positive. As to p16 overexpression, 17 studies (n=1684) used a minimum of 5-69% staining, and 7 studies (n=764) used ≥70% staining. Fifteen studies (n=1478) referred to a verbal definition. Studies showed high heterogeneity in diagnostics of HPV and definition of p16. The correlation between HPV positivity and p16 overexpression proved best numerically in the group applying ≥70% staining for p16 overexpression. The group with verbal definitions had a significantly lower false-positive rate, but along with the group applying 5-69% staining showed a worse sensitivity compared with ≥70% staining. CONCLUSIONS: There are substantial differences in how studies diagnose HPV and define p16 overexpression. Numerically, p16 staining is better to predict the presence of HPV (i.e. larger sensitivity), when the cutoff is set at ≥70% of cytoplasmatic and nuclear staining.