Background:
Elevated free fatty acid (FFA) levels have been shown to increase cardiac repolarization time and are a hypothesized mediator of arrhythmic death. However, as albumin binds and transports FFA, it has been argued that it is the ratio of serum FFA to serum albumin (SA) that is critical. As FFA are chronically elevated in type 1 diabetes and form a major part of the counterregulatory response to hypoglycemia, we investigated the association of the FFA-to-SA ratio with the corrected Q-T (Q-Tc) interval in 87 men and 96 women with type 1 diabetes from the Pittsburgh Epidemiology of Diabetes Complications Study. We also investigated whether this relationship varied by cardiac autonomic neuropathy (CAN: R-R interval<1.1) status.
Methods:
FFAs were measured using a colorimetric method in participants with a mean age and diabetes duration of 44 and 33 years, respectively. The corrected Q-T interval was calculated using Hogdes formula and the FFA-SA ratio determined as FFA (mmol/L) ÷ SA (mg/dL). Because of the sexual dimorphism in FFA metabolism and the Q-T interval, analyses were also conducted sex-specifically.
Results:
Mean (std) FFA levels were 0.95 (o.48) mmol/l and did not vary by sex (men vs women: 0.93 (0.46) vs 0.96 (0.49) mmol/L, p=0.76). The FFA-SA ratio demonstrated a modest association with Q-Tc interval in men (r=0.23, p=0.03), but no association in women (r=-0.07, p=0.48). Overall, in multivariable analyses controlling for sex, visceral adipose tissue, blood glucose levels and albumin excretion rate, FFA-SA, and CAN, a significant interaction was observed between the FFA-SA ratio and CAN in the association of the Q-Tc interval (p=0.03). FFA remained significantly associated with the Q-Tc interval in those without CAN (p<0.05), but not in those with CAN (p=0.30). Sex-specific analyses revealed that although no significant FFA-SA ratio and CAN interaction was observed in men (p=0.42), a relationship between the FFA-SA ratio and Q-Tc interval existed in men free of CAN (p=0.04). No association was observed in women with or without CAN.
Conculsion:
We conclude that a higher FFA-SA ratio is associated with an increased time to cardiac repolarization in those without CAN, particularly in men, helping to explain why the "dead in bed" syndrome is predominantly seen in men.