Effect of obesity and type 2 diabetes on protein anabolic response to insulin in elderly women

Obesity and type 2 diabetes have been shown to alter the insulin sensitivity of glucose and protein metabolism in middle-aged women. We aimed to determine whether these findings translate to the elderly who are at increased risk of muscle loss. We assessed whole-body protein (1-13C-leucine) and glucose (3-3H-glucose) kinetics in 10 healthy (age: 71.6 ± 1.8 years; BMI: 23.2 ± 0.8 kg/m2), 8 obese (age: 72.9 ± 1.3; BMI: 33.1 ± 1.0) and 8 obese well-controlled type 2 diabetic (age: 69.8 ± 1.6; BMI: 34.4 ± 1.5) elderly women in the postabsorptive state and during a hyperinsulinemic, euglycemic, isoaminoacidemic clamp. All subjects followed an isoenergetic, protein-controlled diet for 6 days preceding the clamp. The net protein anabolic response to hyperinsulinemia was similarly blunted in obese (0.08 ± 0.06) and obese type 2 diabetic women (0.06 ± 0.04) compared to healthy women (0.24 ± 0.05 μmol·kg fat free mass− 1·min− 1; ANOVA p = 0.018). In contrast, the insulin-mediated glucose disposal (healthy: 9.72 ± 0.67) was decreased with obesity (6.96 ± 0.86) and further with diabetes (5.23 ± 0.27 mg·kg fat free mass− 1·min− 1; ANOVA p < 0.001). Endogenous glucose production was not completely suppressed during the clamp only in diabetic women. Thus, the glucose infusion rate was the lowest in this group. Obese elderly women with and without type 2 diabetes have a similar degree of insulin resistance of protein anabolism, despite worse glucose metabolism in type 2 diabetes. Similar to previous findings in middle-aged women, obesity exerted a blunting effect on protein anabolism, which may contribute to the development of sarcopenic obesity. Our results suggest that the presence of type 2 diabetes at an advancing age does not further aggravate this effect.