Insulin Sensitivity, Glucose - and Fat Metabolism in Patients With Psoriasis

Background Psoriasis is a chronic immune-mediated inflammatory disease characterized by uncontrolled proliferation of keratinocytes, activated dendritic cells, release of pro-inflammatory cytokines and recruitment of T-cells to the skin. The prevalence of psoriasis is 2-3% worldwide, with similar frequencies in men and women. Psoriasis has been associated with components of the metabolic syndrome, in particular obesity and type 2 diabetes, and patients with psoriasis are at increased risk of developing type 2 diabetes. Obesity is twice as prevalent in patients with psoriasis and patients are at increased risk of developing cardiovascular disease compared to the general population. These co-morbidities are important to recognize or preferably prevent and treat as they might lead to increased mortality.

Type 2 diabetes is a complex metabolic disorder that develops as a consequence of genetic and environmental factors such as inadequate physical activity and obesity. The incidence of type 2 diabetes is increasing worldwide and there is a general agreement that it is caused mainly by the adoption to westernized, sedentary lifestyle. Patients with type 2 diabetes are characterized by decreased peripheral and hepatic insulin sensitivity, beta cell dysfunction and impaired glucose and fat oxidation. Muscle insulin resistance has been proposed to account for as much as 85-90% of the impairment of the peripheral insulin sensitivity (expressed as the total body glucose disposal) in patients with type 2 diabetes during insulin stimulation. Multiple intramyocellular defects have been demonstrated, including impaired glucose transport and phosphorylation, reduced glycogen synthesis, and decreased glucose oxidation as well as proximal defects in the insulin signal transduction system. Similar to psoriasis, systemic inflammation occurs in patients with type 2 diabetes.

The pathophysiological mechanisms explaining the association between psoriasis and type 2 diabetes are largely unknown but it has been hypothesized that systemic inflammation found in both psoriasis and type 2 diabetes might play a role. In a recent study hyperinsulinaemic euglycaemic clamps were made and it showed that normal glucose-tolerant patients with moderate to severe psoriasis had lower whole-body insulin sensitivity during insulin stimulation compared to healthy matched controls. Thus, the increased risk of type 2 diabetes in patients with psoriasis appears to include defects in the glucose metabolism linked to psoriasis itself. However, the methods applied did not allow a detailed characterization of the metabolism in patients with psoriasis. Tracer technique combined with indirect calorimetry has never been applied to study hepatic and whole body insulin sensitivity, and glucose and fat oxidation, during basal conditions or during insulin stimulation in patients with psoriasis.

Methods:

Prior to experimental day 1 and 2 the participants will meet in the morning following a 10 hour fast (including liquids, medication, and tobacco). No alcohol consumption or vigorous physical activities will be permitted 48 hours before the examination, and all participants will be requested to eat carbohydrate-rich diet the previous two days. All experiments will be carried out in the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark where the necessary equipment is available.