The role of incretins in cardiovascular control.

Glucagon-like peptide-1 (GLP-1) is an incretin secreted in response to nutrient ingestion. Understanding the incretin effect on diabetes pathophysiology has led to development of a new class of agents termed incretin mimetics. Exenatide is the first GLP-1 agonist approved to treat type 2 diabetes mellitus (T2DM). Clinical studies have demonstrated exenatide's efficacy in improving glycemic control, often coupled with weight loss. Studies are investigating the potential cardiovascular benefits of GLP-1 agonists. Blood pressure, cholesterol levels, C-reactive protein, and insulin resistance may improve in patients treated with exenatide. The direct effect of GLP-1 on cardiac myocytes and vascular smooth muscle has been an active area of investigation. Infusions of GLP-1 in animal models and human subjects with heart failure have demonstrated significantly improved cardia parameters. In patients with T2DM, GLP-1 infusion has been shown to improve endothelial function, irrespective of changes in insulin sensitivity. These pilot studies provide a foundation for developing therapies aimed at modulating incretin physiology for the additional benefit on the cardiovascular system in patients with T2DM and heart disease.

Exenatide as a treatment for diabetes and obesity: implications for cardiovascular risk reduction.

Among the challenges in improving outcomes in patients with diabetes is effectively implementing existing pharmacotherapies. However, current therapies for diabetes are often limited by adverse effects such as edema, hypoglycemia, and weight gain. Understanding the role of the incretin effect on the pathophysiology of diabetes has led to the development of new therapeutic agents. Exenatide is the first in a new class of agents termed "incretin mimetics," which replicate several glucoregulatory effects of the endogenous incretin hormone, glucagon-like peptide-1. In clinical trials, patients with type 2 diabetes treated with exenatide demonstrate sustained improvements in glycemic control, with reductions in fasting and postprandial glucose levels and improvements in glycosylated hemoglobin levels. Improvements in glycemic control with exenatide are coupled with reductions in body weight. Lipid parameters, blood pressure, and C-reactive protein have been shown to improve favorably in patients treated with exenatide. The sustained glycemic improvements and progressive reduction in body weight with exenatide treatment support a shift toward a more favorable cardiovascular risk profile and may have a positive impact on decreasing the risk of associated long-term complications.

Ocular findings in children with congenital sensorineural hearing loss.

OBJECTIVE: To examine the yield of ophthalmologic examination in the diagnostic workup of unexplained sensorineural hearing loss (SNHL) in children. DESIGN: Retrospective analysis of ophthalmologic findings in children with unilateral or bilateral SNHL between January 1998 and May 2000. SETTING: Tertiary care university hospital. PARTICIPANTS: Children 18 years or younger presenting with unilateral or bilateral SNHL. OUTCOME MEASURES: Ophthalmologic findings. RESULTS: Of the 49 patients with SNHL for whom ophthalmologic examination results were available, 15 (31%) had ocular abnormalities. Hyperopia was the most common abnormality, present in 7 patients (46%). Myopia was found in 2 patients (13%) and astigmatism in 1 (2%). Two other patients had multiple abnormalities: one with hyperopia and astigmatism and the other with myopia and astigmatism. The remaining 4 patients had the following abnormalities: Lisch nodules, esotropia, ptosis, and allergic conjunctivitis. As a result of ophthalmologic examination, 5 interventions were performed in 4 children: 2 children received prescription lenses; 2 children underwent surgery; and 1 child was treated with eyedrops. Ophthalmologic examination in 2 children contributed to the diagnosis of a hearing loss syndrome. CONCLUSION: In children with SNHL, ophthalmologic examination is useful in evaluating visual acuity and determining or confirming the cause of hearing impairment.

Use of laboratory evaluation and radiologic imaging in the diagnostic evaluation of children with sensorineural hearing loss.

OBJECTIVE: Laboratory testing and radiologic imaging are commonly used to delineate syndromic from nonsyndromic sensorineural HL (SNHL). The aim of this study was to examine the yield of laboratory tests and radiologic imaging commonly used in the diagnostic evaluation of SNHL in children. STUDY DESIGN: Retrospective analysis of 114 (54 female, 60 male) consecutively investigated children with SNHL between 1998 and 2000 at a tertiary-care university hospital. METHODS: Results of routine laboratory testing to assess autoimmunity, blood dyscrasias, endocrine abnormalities, renal function, infection, and cardiac testing were reviewed. Results of radiologic evaluation were also reviewed. In general, computed tomography (CT) was obtained in patients with symmetric SNHL, whereas magnetic resonance imaging (MRI) with or without CT was obtained in asymmetric SNHL. RESULTS: Laboratory evaluation of the blood did not yield the etiology of SNHL in any patient. Blood tests for autoimmune disease were often positive but did not correlate with clinical disease. Nonspecific elevation of erythrocyte sedimentation rate (ESR) and antinuclear antibody (ANA) was present in 22% of cases. An abnormal electrocardiogram with a prolonged QT interval resulted in the diagnosis of Jervall and Lange-Nielsen syndrome. In the 97 patients who underwent radiologic studies, abnormalities were present in 38 of 97 studies (39%). Isolated inner ear malformations were twice as common as multiple abnormalities with large vestibular aqueducts as the most common isolated finding. CONCLUSION: In the evaluation of children with unexplained SNHL, routine laboratory evaluation should be reconsidered given its low diagnostic yield. However, radiologic abnormalities of the inner ear are common. Identification of inner ear malformations has direct impact on management of these children, suggesting that all children should undergo radiologic imaging as an integral component of evaluation of SNHL.