QT prolongation is frequently observed in obesity with and without the metabolic syndrome and can be reversed by long term weight reduction

Abstract

Background: Prolongation of the QT interval has been related to various components of the metabolic syndrome (MetS), including type 2 diabetes and obesity. The underlying mechanisms of the QTc prolongation in these subjects are still unknown. We conducted a prospective study to determine ventricular repolarization in parallel to detailed metabolic parameters during the course of a standardized weight reduction. Methods: In a prospective longitudinal study the QTc-interval (QTc) was determined in severely obese subjects (n= 221, mean BMI 40,8±8,2 kg/m2) with and without the Mets (as defined by NCEP ATPIII guidelines) before and after marked weight loss (mean 15,9±11,9 kg). In addition, age-and sex matched healthy lean subjects (n=66) served as controls. Results: The QTc in the obese was significantly longer than in controls (420±26 vs. 408±24 ms, p=0.002). This difference could be observed in obese with the MetS (422±26 ms, p=0.0007), and in healthy obese without any component of the MetS (417±27 ms, p<0.05), but was more pronounced in subjects with insulin resistance (423±28 ms, p=0.0005). Patients with QTc prolongation >440 ms (n=44) had a significantly higher BMI, higher fasting glucose and HOMA levels, but lower serum calcium levels (2.27±0.12 vs. 2.33±0.11 mmol/L, p<0.01) and elevated serum alkaline phosphatase concentrations (79±20 vs. 71±18 U/l, p<0.01), implicating impaired calcium/phosphate metabolism in the obese. During the course of weight reduction the QTc was found to be almost paralleled to BMI. There was a significant correlation between the deltas-over-baseline of BMI, calcium levels (inverse, p=0.0002), and QTc (p=0.0016). While successful weight reduction (i.e. BMI reduction >5 kg/m2) decreased the QTc by 9±5 ms (p<0.01), and increased calcium levels by 0.02±0.01 mmol/L (p=0.0013), these parameters were unchanged after unsuccessful weight reduction. Conclusion: QT prolongation is a common finding in severe obesity and is associated with lower serum calcium levels, probably due to impaired calcium/phosphate metabolism. Interestingly, both QTc time and calcium levels can be positively influenced by successful weight reduction in these subjects.