Psoriasis and the risk of diabetes: A prospective population-based cohort study

Wan, Marilyn T.; Shin, Daniel B.; Hubbard, Rebecca A.; Noe, Megan H.; Mehta, Nehal N.; Gelfand, Joel M.

doi:10.1016/j.jaad.2017.10.050

Cited by 90 publications

(81 citation statements)

References 35 publications

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“…As alluded to above, epidemiological studies have revealed a positive correlation between psoriasis disease severity and risk of developing T2D . In five of the HOMA‐IR studies mentioned above, the mean PASI of the included patients was high (> 8), reflecting severe disease .…”

Section: Overview Of the Clinical Studiesmentioning

confidence: 93%

“…As mentioned briefly in the introduction, the evidence from the epidemiological literature has suggested that psoriasis is associated with T2D and, intriguingly, that there exists a dose–response effect with more severe psoriasis associated with a higher risk of T2D . Three comprehensive meta‐analyses all found a significant association between psoriasis and the prevalence and/or incidence of diabetes .…”

Section: Epidemiological Studies On the Association Between Psoriasismentioning

confidence: 99%

“…Epidemiological studies strongly support an association between psoriasis and T2D, and several lines of evidence point to a dose–response effect, with more severe psoriasis associated with a higher risk of T2D . Thus, epidemiological data firmly suggest that psoriasis predisposes to T2D, but the pathophysiological link between psoriasis and T2D is, as yet, poorly understood.…”

mentioning

confidence: 99%

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Glucose metabolism in patients with psoriasis

et al. 2018

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Summary 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.

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Section: Overview Of the Clinical Studiesmentioning

confidence: 93%

Section: Epidemiological Studies On the Association Between Psoriasismentioning

confidence: 99%

mentioning

confidence: 99%

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Glucose metabolism in patients with psoriasis

et al. 2018

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“…The skin lesions in psoriasis manifest as scaly multiple erythema on the face, scalp, trunk and upper and lower extremities, which places a significant physical and psychological burden on affected patients, resulting in a decreased quality of life 4 . Psoriasis frequently coexists with other systemic diseases such as type 2 diabetes mellitus (T2DM) [5][6][7][8] , arterial hypertension 9,10 , obesity [11][12][13] and cardiovascular disease [14][15][16] . Several retrospective epidemiological studies have shown the association of T2DM with psoriasis and suggested that there is a severity-dependent relationship 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Metformin inhibits IL-1β secretion via impairment of NLRP3 inflammasome in keratinocytes: implications for preventing the development of psoriasis

Tsuji

Hashimoto-Hachiya

et al. 2020

Cell Death Discov.

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Psoriasis is a systemic inflammatory disease significantly associated with comorbidities including type 2 diabetes mellitus (T2DM). Metformin is utilized as a first-line agent for treating T2DM. Although metformin reportedly inhibits mature IL-1β secretion via NLRP3 inflammasome in macrophages of T2DM patients, it remains unclear whether it affects skin inflammation in psoriasis. To test this, we analysed normal human epidermal keratinocytes (NHEKs), a major skin component, stimulated with the key mediators of psoriasis development, TNF-α and IL-17A. This stimulation induced the upregulation of pro-IL-1β mRNA and protein levels, and subsequently mature IL-1β secretion, which was inhibited by metformin treatment. To further reveal the mechanism involved, we examined how metformin treatment affected NLRP3 inflammasome activated by TNF-α and IL-17A stimulation. We found that this treatment downregulated caspase-1 expression, a key mediator of NLRP3 inflammasome. Furthermore, inhibitors of AMPK and SIRT1 abrogated the downregulation of caspase-1 induced by metformin treatment, indicating that AMPK and SIRT1 are essential for the inhibitory effect on NLRP3 inflammasome in NHEKs. As IL-1β stimulation induced upregulation of IL-36γ, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels in NHEKs, we examined whether metformin treatment affects such gene expression. Metformin treatment inhibited upregulation of IL-36γ, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels induced by TNF-α and IL-17A stimulation. Finally, we examined whether metformin administration affected psoriasis development in an imiquimod-induced mouse psoriasis model. Oral metformin treatment significantly decreased ear thickness, epidermal hyperplasia and inflammatory cell infiltration. A cytokine profile in the epidermis under metformin treatment showed that IL-1β, Cxcl1, Cxcl2, S100a7, S100a8 and S100A9 mRNA levels were downregulated compared with control levels. These results indicate that metformin administration prevented psoriasis development in vivo. Collectively, our findings suggest that metformin-mediated anti-psoriatic effects on the skin have the potential for treating psoriasis in T2DM patients.

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“…In patients with psoriasis who are treated with CsA, nephrotoxicity is associated with longer term administration, a larger cumulative dose, and a higher daily dose (Coresh et al, 2001). Other risk factors include older age, male sex, obesity, hypertension (HTN), diabetes mellitus (DM), and concomitant use of nephrotoxic drugs (Colombo, Cassano, Bellia, & Vena, 2013;El-Bassossy & Eid, 2018;Kim et al, 2017;Maza et al, 2011;Rodier, Ribstein, Parer-Richard, & Mimran, 1991;Wan et al, 2018). Although intermittent treatment with CsA with 12-week courses has been generally recommended, there is still controversy regarding the optimal treatment strategy to prevent CsA nephrotoxicity (Colombo et al, 2013;Nast et al, 2015).…”

mentioning

confidence: 99%

Risk factors for increased serum creatinine level in patients with psoriasis treated with cyclosporine in a real‐world practice

Hong

Lee

Choe

et al. 2019

Dermatologic Therapy

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Nephrotoxicity is a major concern for patients with psoriasis using cyclosporine. Here, we evaluated the impact of intermittent cyclosporine treatment on nephrotoxicity risk among patients with psoriasis in real‐world clinical practice. We retrospectively reviewed 611 patients with psoriasis treated with cyclosporine between January 2013 and January 2017, 398 of whom were considered eligible for analysis. Eighteen (4.5%) patients showed a greater than 25% increase in serum creatinine levels. Age over 60 years (relative risk [RR], 1.6; p = .015), diabetes (RR, 2.3; p < .001), and obesity (RR, 1.7; p = .011) were the significant risk factors of increased serum creatinine levels in patients with psoriasis. There was no significant association of the treatment duration or cumulative dose of cyclosporine with increased serum creatinine levels. In real clinical practice, intermittent cyclosporine use with regular serum creatinine tests can be used to treat psoriasis relatively safely. Age over 60 years, diabetes and obesity are significant risk factors for cyclosporine‐induced nephrotoxicity.

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Psoriasis and the risk of diabetes: A prospective population-based cohort study

Abstract: Clinicians may measure BSA affected by psoriasis to target diabetes prevention efforts for patients with psoriasis.

Cited by 90 publications

References 35 publications

Glucose metabolism in patients with psoriasis

Glucose metabolism in patients with psoriasis

Metformin inhibits IL-1β secretion via impairment of NLRP3 inflammasome in keratinocytes: implications for preventing the development of psoriasis

Risk factors for increased serum creatinine level in patients with psoriasis treated with cyclosporine in a real‐world practice

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