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1T he roles of insulin deficiency and t reatment in protein homeostasis are well documented in type 1 diabetes (1-8) but insulin' s role in type 2 diabetes remains uncertain. The American Diabetes Association recently concluded that t h e re were insufficient data on which to make firm dietary protein re c o m m e n d ations (9), and one expert renewed the call for more re s e a rch (10). We have re p o rt e d that protein metabolism is accelerated in moderately hyperglycemic obese diabetic subjects when compared with an obese c o n t rol group during a weight-maintaining diet with ample protein intake (11). These alterations were corrected with euglycemia from exogenous insulin (12, 13). However, euglycemia with a veryl o w -e n e rgy diet (VLED) did not completely reestablish nitrogen equilibrium in diabetic, in contrast to nondiabetic, subjects. This suggested that type 2 diabetic subjects have altered adaptive mechanisms for protein sparing, independent of the protein quality (11,12). When glycemia was normalized with insulin at the onset of the VLED, nitrogen balance was i m p roved but equilibrium was still not achieved (13). The question re m a i n e d whether protein metabolism and nitro g e n balance could be corrected using the conventional approach to treatment that combines moderate energy restriction with oral hypoglycemic agents (OHA). We investigated the effects of OHA on pro t e i n metabolism during both isoenergetic feeding (ISO) and 4 weeks of energy re s t r i ction or low-energy diet (LED). With ISO, we aimed for the best possible glycemic c o n t rol, whereas with LED, the goal was e u g l y c e m i a . RESEARCH DESIGN AND M E T H O D SSubjects A total of 13 obese subjects with type 2 diabetes (7 women, 6 men) and 10 obese nondiabetic control subjects (9 women, 1 man) were admitted to the Clinical Investigation Unit of the Royal Victoria Hospital ( Table 1). OHAs were stopped 1 week bef o re admission. Consent was obtained acc o rding to the Institutional Human Ethics Committee. Clinical and laboratory evaluations showed no evidence of hepatic, card i o v a s c u l a r, hematologic, renal or pulm o n a ry dysfunction, or gout. The subjects p e rf o rmed two half-hour walks each day. The ISO diet was a weight-maintaining liq- A d d ress correspondence and reprint requests to Dr. Réjeanne Gougeon, McGill Nutrition and Food Science C e n t re, Royal Victoria Hospital, 687 Pine Ave. W., Montréal, Québec, Canada H3A 1A1. E-mail: rg o u g e o n @ rv h m e d . l a n . m c g i l l . c a .Received for publication 15 March 1999 and accepted in revised form 22 September 1999. A b b re v i a t i o n s :3MH, N -methylhistidine; B, protein breakdown; BMI 2 5 , body weight corresponding to a BMI of 25; FFM, fat-free mass; FSG, fasting serum glucose; ISO, isoenergetic diet; LED, low-energy diet; OHA, oral hypoglycemic agent; Q, nitrogen flux; S, protein synthesis; S-B, net protein synthesis; VLED, v e ry -l o w -e n e rgy diet.A table elsewhere in this issue shows conventional and Système International (SI...

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