Henri Wallaschofski

Adiponectin in patients with obstructive sleep apnea syndrome: Course and physiological relevance

Background: Adiponectin is an adipocyte-derived hormone with anti-inflammatory and insulin-sensitizing properties. Insulin resistance is a typical feature of the obstructive sleep apnea syndrome (OSAS). Objectives: Since nasal continuous positive airway pressure (nCPAP) treatment improves insulin sensitivity in patients with OSAS, we investigated serum adiponectin levels before and during nCPAP treatment to clarify possible interactions between the adiponectin levels and insulin sensitivity in patients with OSAS. Methods: Thirty nondiabetic, obese patients with OSAS (mean age 56.4 ± 11.1 years; apnoea-hypopnoea index (AHI) 46.03 ± 19.57) underwent CPAP treatment. Adiponectin levels and the levels of proinflammatory cytokines and proteins reflecting platelet activation [regulated on activation normally T cell expressed and secreted (RANTES) and soluble P-selectin (sCD62p)], as well as the insulin sensitivity index were measured before, and after 2 days and 3 months of CPAP treatment. Results: Insulin sensitivity increased significantly under nCPAP treatment, whereas adiponectin levels decreased after 2 days of nCPAP treatment, but returned to baseline levels after 3 months of nCPAP treatment. The increase in insulin sensitivity was more pronounced in patients with the highest adiponectin levels at baseline (p = 0.021) after adjustment for body fat (p = 0.003). During treatment, changes in adiponectin levels were highly predictable by the insulin sensitivity index. Conclusions: We found a significant relation between adiponectin and the insulin sensitivity index in overweight patients with OSAS. The lack of a long-lasting change in adiponectin may be explained by the overwhelming influence of the body mass index on adiponectin secretion, which was unchanged during nCPAP treatment.

Hyperprolactinemia in patients on antipsychotic drugs causes ADP-stimulated platelet activation that might explain the increased risk for venous thromboembolism: Pilot study

Recently, an increased risk of venous thromboembolism in patients on antipsychotic drugs has been reported, but the molecular etiology is still unknown. Most antipsychotic drugs act as dopamine antagonists, and some of them cause hyperprolactinemia. Hyperprolactinemia has recently been found to cause increased platelet activation via potentiating ADP effects on human platelets. We assessed prolactin values as well as ADP-stimulated and thrombin receptor activator 6-stimulated expression of the platelet activation marker P-selectin in 20 consecutive patients under therapy with antipsychotic drugs. We detected a significant correlation between prolactin values and ADP-stimulated P-selectin expression on platelets in patients on antipsychotic drugs, revealing a significant higher platelet stimulation in hyperprolactinemic patients on antipsychotic drugs than in normoprolactinemic controls. Therefore, hyperprolactinemia might be the yet unknown acquired risk factor in patients on antipsychotic drugs explaining the increased risk for venous thromboembolism in these patients.

Adiponectin in obese patients with obstructive sleep apnoea syndrome

Adiponectin in obese patients with obstructive sleep apnoea syndrome Aims: Adiponectin is an adipocyte-derived hormone with anti-inflammatory and insulin-sensitizing properties. Insulin resistance is a typical feature of the obstructive sleep apnoea syndrome (OSAS). Objectives: Since nasal continuous positive airway pressure (CPAP) treatment improves insulin sensitivity in patients with OSAS, we investigated the changes of serum adiponectin levels before and during nCPAP treatment to clarify possible interactions between the adiponectin levels and insulin sensitivity in patients with OSAS. Objectives and Methods: Thirty non-diabetic, obese patients with OSAS (mean age: 56.4±11.1 years; AHI: 46.03±19.57) underwent nCPAP treatment. Adiponectin levels, as well as the levels of proinflammatory cytokines and proteins reflecting platelet activation RANTES (Regulated on Activation Normally T-cell Expressed and Secreted) and soluble P-selectin (sCD 62p), as well as the insulin sensitivity index (ISI), measured by hyperinsulinemic euglycemic clamp, were measured before, and after 2 days and 3 months of CPAP treatment. Results: Insulin sensitivity increased significantly under nCPAP treatment, whereas adiponectin levels decreased after 2 days of nCPAP treatment, but returned to baseline levels after 3 months of nCPAP treatment. The increase of insulin sensitivity was more pronounced in patients with the highest adiponectin levels at baseline (p=0.021) after adjustment for body fat (p=0.003). During treatment, changes in adiponectin levels were highly predictable by ISI. Conclusions: We found a significant relation between adiponectin and ISI in overweight patients with OSAS. The lack of a long-lasting change in adiponectin may be explained by the overwhelming influence of BMI on the adiponectin secretion, which was unchanged during nCPAP treatment.