Abstract

We reported insulin resistance of protein metabolism in hyperglycemic type 2 diabetic adults. Resulting inefficient protein utilization could be exacerbated by weight loss diets that keep protein as a fixed % of energy. We tested whether a moderately hypoenergetic, abundant-protein diet could prevent this, while preserving the glucoregulatory improvement. Diet provided 60% of energy requirements, 45% of energy as carbohydrate, 26% as protein (1.9 g/kgLBM/day) for 5 weeks in obese diabetic adults (n=5, 52 to 64 years). Insulin sensitivity of whole-body glucose (3-3H-glucose) and protein (13C-leucine) kinetics were quantified pre- and post-diet, postabsorptive and during hyperinsulinemic (∼500pM), isoglycemic (7.7±0.4 pre vs. 5.7±0.2 mM post), isoaminoacidemic clamps. Weight loss was 5.3±0.7 kg, as fat 4.0±0.3 kg (both p<0.004) and LBM 1.2±1.0 kg (NS), and RMR/LBM maintained. The following decreased post-diet (p<0.05): postabsorptive glycemia (7.7±0.4 to 5.7±0.2 mM), insulin (109±17 to 69±8 pM), HOMA-IR (6.2±1.0 to 2.9±0.4), A1C (7.6 to 6.6%) and antihypertensive and/or diabetes medications. Whereas glucose Ra and Rd (1.9±0.2 mg/kgBW/min) did not change, MCR (Rd/glycemia) increased. Notably, protein catabolism and oxidation decreased, resulting in less negative net balance (p<0.05). Clamp glucose Ra and Rd responses did not improve, but MCR increased from 2.3±0.2 to 3.5±0.4 mL/kg∙min (p=0.01); protein catabolism was suppressed but synthesis not stimulated, resulting in no net anabolism improvement. Weight lost was fat, lean mass preserved, fasting glycemia, insulin and protein balance improved. In response to hyperinsulinemia, only MCR improved, but protein metabolism did not worsen. Thus, abundant protein appears to preserve body proteins in the face of energy deficit and insulin resistance.

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