Although obesity is strongly associated with cardiovascular disease (CVD), the endogenous relationship between obesity and CVD is still not fully clear. Emerging evidence from both animal and human studies indicates that leptin may play an important role in obesity-related CVD. Besides modulating appetite and metabolism, leptin has also been shown to increase sympathetic nerve activity, stimulate generation of reactive oxygen species, upregulate endothelin-1 production and potentiate platelet aggregation. These effects of leptin may contribute to hypertension, endothelial dysfunction and atherosclerosis in obese individuals. Better understanding the mechanisms of leptin resistance should facilitate therapeutic approaches to reverse the phenomenon of selective leptin resistance. These recent discoveries could lead to novel strategies for treatment of obesity-associated CVD.
Drug-induced weight gain is a serious side effect of many commonly used drugs leading to noncompliance with therapy and to exacerbation of comorbid conditions related to obesity. Improved glycemic control achieved by insulin, insulin secretagogues or thiazolidinedione therapy is generally accompanied by weight gain. It is a problematic side effect of therapy due to the known deleterious effect of weight gain on glucose control, increased blood pressure and worsening lipid profile. Weight gain may be lessened or prevented by adherence to diet and exercise or combination therapy with metformin. Weight gain is also common in psychotropic therapy. The atypical antipsychotic drugs (clozapine, olanzepine, risperidone and quetiapine) are known to cause marked weight gain. Antidepressants such as amitriptyline, mirtazapine and some serotonin reuptake inhibitors (SSRIs) also may promote appreciable weight gain that cannot be explained solely by improvement in depressive symptoms. The same phenomenon is observed with mood stabilizers such as lithium, valproic acid and carbamazepine. Antiepileptic drugs (AEDs) that promote weight gain include valproate, carbamazepine and gabapentin. Lamotrigine is an AED that is weight-neutral, while topiramate and zonisamide may induce weight loss.
September 10-15, 2005, the European Association for the Study of Diabetes held its 41st Annual Meeting in Athens, Greece. This meeting was devoted to new developments in understanding, diagnosis and management of diabetes mellitus and related disorders. Each day's program included plenary sessions, symposia, oral presentations, poster discussions, lectures, current issues and supportive care. This article highlights recent developments in pathophysiology, new therapeutic possibilities and preventive aspects of cardiovascular diseases in diabetes mellitus.
Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide that belongs to a family of structurally related peptide hormones including pituitary adenylate cyclase-activating peptide (PACAP). These hormones are widely distributed in the nervous system, where they act as neurotransmitters. Their biological effects are mediated by specific receptors, VPAC1 and VPAC2, which have comparable affinity for VIP and PACAP, and PAC1, which binds VIP with 1,000-fold lower affinity than PACAP. Both peptides are involved in autonomic regulation of the cardiovascular system, where they exert positive inotropic and chronotropic effects, and cause coronary vasodilatation. Additionally, PACAP inhibits proliferation of cardiac fibroblasts. Several cardiovascular diseases, such as myocardial fibrosis, heart failure, cardiomyopathy and pulmonary hypertension, have been found to be associated with changes in myocardial VIP concentration or with alteration of affinity, density and physiological responsiveness of VIP/PACAP receptors. Application of the peptides or their agonists has beneficial effect in hypertension, heart failure and myocardial fibrosis. Taken together, VIP and PACAP have beneficial effects in various pathological conditions.
The treatment of atrial fibrillation still remains challenging in everyday practice. Even after the introduction of catheter ablation, the decision making about the type of therapy became more complex. The recently published guidelines of the American Heart Association, the American College of Cardiology and the European Society of Cardiology clearly show therapeutic approaches for different types of atrial fibrillation. The fear of thromboembolism still forces the physician to restore sinus rhythm and perform a perfect anticoagulation. Based on large studies, we are able to decide for each patient individually whether oral anticoagulation or aspirin is required. Future studies in a large cohort of patients are still necessary to clarify the value of interventional therapy in conjunction with antiarrhythmic drug therapy. These will provide patients with safe therapy and a high quality of life despite presenting paroxysmal or persistent atrial fibrillation.