incretins and Psoriasis

This brief review describes the potential non-glycaemic effects and benefits of glucagon like peptide 1 receptor agonists (GLP1RA). It lists various indications in which this class of drugs has been used, and explains the rationale behind this use. The potential uses of GLP1RA extend across the entire spectrum of endocrinology and metabolism, from hypothalamic obesity to non-alcoholic steatohepatitis (NASH) to polycystic ovary syndrome (PCOS). The article also discusses and addresses endocrine-related concerns related to the GLP1RAs.

Topics: Bone and Bones; Central Nervous System; Diabetes Mellitus, Type 2; Exenatide; Female; Glucagon-Like Peptide-1 Receptor; Gonads; Humans; Hypothalamic Diseases; Incretins; Liraglutide; Liver; Male; Non-alcoholic Fatty Liver Disease; Obesity; Ovary; Peptides; Polycystic Ovary Syndrome; Psoriasis; Testis; Thyroid Gland; Venoms

Psoriasis is a chronic inflammatory skin disease with a global prevalence of 2-3%. In recent years it has been established that patients with psoriasis carry an increased risk of type 2 diabetes, but the underlying pathophysiological mechanisms remain unclear. The association is most likely due to a combination of shared genes, immunoinflammatory mechanisms and a number of diabetes risk factors in patients with psoriasis. The current review summarises the evidence in the field and calls for attention on diabetes risk assessment, preventive measures and treatment in patients with psoriasis.

Topics: Alcohol Drinking; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucocorticoids; Humans; Incretins; Metabolic Syndrome; Obesity; Psoriasis; Risk Factors; Smoking

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.. 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.. 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.. 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.. 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.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Gastrointestinal Tract; Glucagon; Glucose; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Prediabetic State; Psoriasis; Reproducibility of Results; Severity of Illness Index

A few case reports suggest that incretin-based therapies could improve psoriasis in patients with type 2 diabetes, the mechanism(s) of which remain unclear.. To determine the effects after 16-20 weeks of treatment with a glucagon-like peptide (GLP)-1 analogue on clinical severity and histopathological aspects of psoriasis in patients with type 2 diabetes, and to examine the presence of γδ T cells and the expression of interleukin (IL)-17 in psoriasis before and after treatment.. Seven patients with type 2 diabetes and psoriasis were followed. Psoriasis Area and Severity Index (PASI) was measured at baseline (T0) and after 7 ± 1 (T1) and 18 ± 2 (T2) weeks' treatment with exenatide/liraglutide. The histopathological pattern of psoriasis, and flow cytometry and immunological data (γδ T-cell percentage and IL-17 expression) were obtained from psoriatic and control sites.. The mean PASI decreased from 12·0 ± 5·9 to 9·2 ± 6·4 (P = 0·04). Histological analysis showed a reduction in epidermal thickness after treatment. The dermal γδ T-cell percentage was higher in psoriatic lesions than in control specimens (P = 0·03), as was IL-17 expression (P = 0·018). A reduction of γδ T cells from 6·7 ± 4·5% to 2·7 ± 3·8% (P = 0·05) was demonstrated in the six patients with improved/unchanged PASI. A correlation between PASI and γδ T-cell percentage evolution during therapy (T2-T0) was noted (r = 0·894, P = 0·007). IL-17 was reduced in the four patients with the highest PASI reductions.. The administration of a GLP-1 analogue improved clinical psoriasis severity in patients with type 2 diabetes. This favourable outcome was associated with a decrease of dermal γδ T-cell number and IL-17 expression. Further studies are needed to establish long-term efficacy in (diabetic) patients with psoriasis.

Topics: Adult; Chronic Disease; Diabetes Mellitus, Type 2; Exenatide; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Incretins; Interleukin-17; Liraglutide; Lymphocyte Count; Male; Middle Aged; Peptides; Prospective Studies; Psoriasis; Severity of Illness Index; Skin; T-Lymphocytes; Treatment Outcome; Venoms

Topics: Acitretin; Chronic Disease; Drug Therapy, Combination; Glucagon-Like Peptide 1; Humans; Incretins; Keratolytic Agents; Liraglutide; Male; Middle Aged; Psoriasis