The objective of this study was to determine the effects of weight loss on heart rate variability (HRV) and its association with traditional cardiovascular disease risk factors in overweight and obese patients with type 2 diabetes. Forty five patients [body mass index (BMI) 35.4 +/- 0.7 kg/m(2); age 56.5 +/- 1.1 yr] with type 2 diabetes followed an energy-restricted diet (6-7 MJ/day) for 16 wk. Body weight, blood pressure, glucose, insulin, insulin resistance [homeostasis model assessment index 2 (HOMA2)], glycosylated hemoglobin (HbA1c), total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, resting HR, and HRV were measured before and after the intervention period. Mean reduction in body weight was 11.1 +/- 1.0 kg (10%), with significant reductions in blood pressure (-10%), total cholesterol (-15.9%), LDL (-17.7%), HDL (-7.5%), triglycerides (-21.2%), glucose (-23.4%), insulin (-37.6%), HOMA2 (-40.1%), and HbA1c (-14.5%) (P </= 0.05 for all variables). There were increases in several HRV components, including total power (1,370 +/- 280 to 2,045 +/- 280 ms(2)), low-frequency power (345 +/- 70 to 600 +/- 108 ms(2)), SD of normal to normal intervals (SDNN; 35.0 +/- 2.5 to 43.0 +/- 2.7 s), and square root of the mean squared differences of successive normal to normal intervals (RMSSD; 23.0 +/- 3.5 to 32.0 +/- 3.1 s), and a decrease in HR (69.0 +/- 1.3 to 60.0 +/- 1.2 beats/min) (P </= 0.03 for all variables). Changes in HR, SDNN, total power, and low-frequency power correlated with change in BMI (P < 0.05). In addition to improvements in traditional cardiovascular and metabolic risk factors, weight loss improves HRV in overweight and obese patients with type 2 diabetes.