Insulin resistance in obesity: body-weight or energy balance?

Weight reduction is recommended for the treatment of subjects with insulin resistance (IR) syndrome; however, the relative importance of the decrease in body fat or the negative energy balance achieved during a hypo-energetic diet in the improvement of this metabolic syndrome is still debated. There fore, we undertook to study their relative impact on amelioration of the me tabolic abnormalities associated with IR in obese subjects. Twelve obese subjects (six males and six females, mean +/- S.D. body mass i ndex 36.1 +/- 4.7 kg/m(2)) aged 38-57 years were investigated. During the f irst phase they were fed a hypo-energetic diet for 6 weeks (week 0-6). Duri ng the second phase, lasting 4 weeks (week 6-10) they consumed an iso-energ etic diet. During the third phase (week 10-16) the subjects were put again on a hypo-energetic diet. Insulin sensitivity (SI) was assessed by an insul in-enhanced, frequently sampled i.v. glucose tolerance test with minimal mo del analysis. All subjects reduced weight during both hypo-energetic period s: 5.49 +/- 0.75 and 2.32 +/- 0.37%, means +/- S.E.M., P<0.005, week 0-6 an d 10-16 respectively. One-third of this loss was achieved within the first week of each period. SI increased by 353 +/- 121 and 147 +/- 38% (P<0.005), means +/- S.E.M., at the end of both hypo-energetic periods (week 6 vs 0 a nd 16 vs 10 respectively). Two-thirds of this improvement were observed wit hin the first week of each period (week 1 vs 0 and 11 vs 10 respectively). During the iso-energetic weight-maintaining period (week 10 vs 6), SI decre ased by 43.5 +/- 7.9% (P<0.002). Serum levels of leptin and triglyceride fo llowed a similar pattern, but to a lesser extent. It may be concluded that negative energy balance is more effective when com pared with maintaining a stable lower weight in achieving an improvement in the metabolic parameters of the IR syndrome.