Antibodies against glutamic acid decarboxylase and indices of insulin resistance and insulin secretion in nondiabetic adults: a cross-sectional study.

BACKGROUND: Autoimmunity against insulin-producing beta cells from pancreatic islets is a common phenomenon in type 1 diabetes and latent autoimmune diabetes in adults. Some reports have also related beta-cell autoimmunity to insulin resistance (IR) in type 2 diabetes. However, the extent to which autoimmunity against components of beta cells is present and relates to IR and insulin secretion in nondiabetic adults is uncertain. AIM: To explore the association between antibodies against glutamic acid decarboxylase (GADA), a major antigen from beta cells, and indices of whole-body IR and beta-cell capacity/insulin secretion in adults who do not have diabetes. METHODS: We studied 81 adults of both sexes aged 30-70, without known diabetes or any autoimmune disease. Participants underwent an oral glucose tolerance test (OGTT) with determination of plasma glucose and insulin at 0, 30, 60, 90, and 120 minutes. From these results we calculated indices of insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] and incremental area under the insulin curve [iAUCins]) and insulin secretion (corrected insulin response at 30 minutes and HOMA beta-cell%). GADAs were measured in fasting plasma using immunoenzymatic methods. RESULTS: We found an overall prevalence of GADA positivity of 21.3%, without differences by sex and no correlation with age. GADA titers did not change monotonically across quartiles of any of the IR or insulin secretion indices studies. GADA did not correlate linearly with fasting IR expressed as HOMA-IR (Spearman's r=-0.18, p=0.10) or postabsorptive IR expressed as iAUCins (r=-0.15, p=0.18), but did show a trend toward a negative correlation with insulin secretory capacity expressed by the HOMA-beta cell% index (r=-0.20, p=0.07). Hemoglobin A1c, body mass index, and waist circumference were not associated with GADA titers. CONCLUSION: GADA positivity is frequent and likely related to impaired beta-cell function among adults without known diabetes.

Cardiogenic syncope diagnosed as epileptic seizures: the importance of ECG during video-EEG recording.

We describefourpatientswith a previous diagnosis of epilepsy. After reviewing the ECG during the video-EEG recording, cardiogenic syncope, resulting from a cardiac arrhythmia, was identified as the cause of the seizures. Epileptic disorders and cardiogenic syncope may both manifest with convulsions, loss of consciousness, and loss of postural tone, leading to a high level of misdiagnosis. The one-lead ECG during video-EEG monitoring is a key component, which may allow correct diagnosis and treatment.

Adenosine triphosphate citrate lyase: Emerging target in the treatment of dyslipidemia.

Despite major advances in pharmacologic therapy over the last few decades, dyslipidemia remains a prevalent, insufficiently recognized, and undercontrolled risk factor for cardiovascular disease. Statins are the mainstay of hypercholesterolemia treatment, but because of adherence and tolerability issues that limit dose titration, there is a need for additional therapies with good efficacy and better tolerability. Adenosine triphosphate (ATP) citrate lyase, a cytoplasmic enzyme responsible for the generation of acetyl coenzyme A for the de novo synthesis of fatty acids and cholesterol, is a very interesting molecular target for the reduction of plasma lipids. Furthermore, ATP citrate lyase inhibition may be accompanied by activation of 5'-adenosine monophosphate-activated protein kinase, a key signaling molecule that acts a central hub in cellular metabolic regulation. ETC-1002 is a small molecule inhibitor of ATP citrate lyase that also activates 5'-adenosine monophosphate-activated protein kinase, effectively reducing low-density lipoprotein cholesterol and inducing some other positive metabolic changes. Recent evidence from phase I and II clinical trials in humans has shown a positive efficacy and safety profile of ETC-1002, with low-density lipoprotein cholesterol reductions similar to those attainable by usual doses of many statins and with no major apparent side effects. These results potentially introduce a new family of medications that may expand our therapeutic arsenal against hypercholesterolemia.