A number of clinical studies have reported that diabetes mellitus (DM) is an independent risk factor for Atrial fibrillation (AF). After adjustment for other known risk factors including age, sex, and cardiovascular risk factors, DM remains a significant if modest risk factor for development of AF. The mechanisms underlying the increased susceptibility to AF in DM are incompletely understood, but are thought to involve electrical, structural, and autonomic remodeling in the atria. Electrical remodeling in DM may involve alterations in gap junction function that affect atrial conduction velocity due to changes in expression or localization of connexins. Electrical remodeling can also occur due to changes in atrial action potential morphology in association with changes in ionic currents, such as sodium or potassium currents, that can affect conduction velocity or susceptibility to triggered activity. Structural remodeling in DM results in atrial fibrosis, which can alter conduction patterns and susceptibility to re-entry in the atria. In addition, increases in atrial adipose tissue, especially in Type II DM, can lead to disruptions in atrial conduction velocity or conduction patterns that may affect arrhythmogenesis. Whether the insulin resistance in type II DM activates unique intracellular signaling pathways independent of obesity requires further investigation. In addition, the relationship between incident AF and glycemic control requires further study.

Cardiac myosin binding protein-C (cMyBP-C) is a heart muscle-specific thick filament protein. Elevated level of serum cMyBP-C is an indicator of early myocardial infarction (MI), but its value as a predictor of future cardiovascular disease is unknown. Based on the presence of significant amount of cMyBP-C in the serum of previous study subjects independent of MI, we hypothesized that circulating cMyBP-C is a sensitive indicator of ongoing cardiovascular stress and disease. To test this hypothesis, 75 men and 83 women of similar ages were recruited for a prospective study. They underwent exercise stress echocardiography to provide pre- and poststress blood samples for subsequent determination of serum cMyBP-C levels. The subjects were followed for 1 to 1.5 years. Exercise stress increased serum cMyBP-C in all subjects. Twenty-seven primary events (such as death, MI, revascularization, invasive cardiovascular procedure, or cardiovascular-related hospitalization) and 7 critical events (CE; such as death, MI, stroke, or pulmonary embolism) occurred. After adjusting for sex and cardiovascular risk factors with multivariate Cox regression, a 96% sensitive prestress cMyBP-C threshold carried a hazard ratio of 8.1 with p = 0.041 for primary events. Most subjects (6 of 7) who had CE showed normal ejection fraction on echocardiography. Pre-stress cMyBP-C demonstrated area under receiver operating curve of 0.91 and multivariate Cox regression hazard ratio of 13.8 (p = 0.000472) for CE. Thus, basal cMyBP-C levels reflected susceptibility for a variety of cardiovascular diseases. Together with its high sensitivity, cMyBP-C holds potential as a screening biomarker for the existence of severe cardiovascular diseases.