High sugar and fat intake as well as low physical activity are known risk factors for the development of insulin resistance and type 2 diabetes. We hypothesize that particular chronic high glucose availability without high metabolic demand might generate metabolic alterations which increase the risk for type 2 diabetes. Therefore a combined diet and exercise intervention should counteract and revert any accumulated health risks related to malnutrition and exercise deficiency. We adopted a low-carbohydrate diet combined with high-intensity interval training (HIT) to improve insulin sensitivity, whole body metabolism and blood lipid profile in overweight sedentary individuals. Overweight sedentary subjects (n=19; BMI=32±3) were randomly assigned to an exercise – diet (DE) or diet only (D) group. Subjects (DE) trained three times a week on a cycle-ergometer (4 min 90% VO2peak, 3 min rest, 10 bouts) for two weeks and followed a low carbohydrate diet (35% carbohydrates, 15% proteins, 50% fats, 33% unsaturated) while the D group followed the diet protocol only. Post intervention Oral Glucose Insulin Sensitivity (OGIS) was significantly improved in both groups (OGIS(ml x min-1 x m-2): DE 377±70 to 396±68; D 365±91 to 404±87), and blood lipids (plasma triglycerides: DE 1.44±1.1 to 1.05±0.74, D 1.33±0.37 to 0.97±0.25; LDL: DE 2.97±0.74 to 2.76±0.66, D 3.43±0.63 to 3.17±0.69 and total cholesterol: DE 4.60±0.94 to 4.24±0.83, D 5.00±0.76 to 4.49±0.88 (mmol/l)) were significantly reduced. Moreover, RER was reduced in both groups (DE 0.91±0.06 to 0.88±0.06, D 0.92±0.07 to 0.86±0.07) while VO2max was increased by 16% in the DE group only. Additionally glycogen levels in muscle biopsies have been reduced in both groups revealing a reduction of glucose availability. It is evident that a low-carbohydrate diet alone can improve important parameters related to insulin resistance and type 2 diabetes while a combination of HIT and diet additionally mediate beneficial cardiovascular adaptations which are known to lower health risks in obese individuals.