Effects of oral hypoglycemic agents and diet on protein metabolism in type 2 diabetes.

Abstract

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...

Long-term effects of advice to consume a high-protein, low-fat diet, rather than a conventional weight-loss diet, in obese adults with Type 2 diabetes: one-year follow-up of a randomised trial

“…This preferential loss of LBM in Type 2 diabetes may be due to a higher whole-body proteolytic rate associated with moderate hyperglycaemia [23]. Our results suggest this effect may occur independently of protein intake although a higher protein intake has previously been shown to suppress proteolysis of lean tissue in obese healthy adults [24].…”

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover

“…We predict that the insulinresistant subjects of these previous studies would have had insulin resistance of protein metabolism, and that treatment with rosiglitazone [5] or metformin [48] would have decreased that resistance, contributing to the decreased plasma ADMA with treatment. We have shown that a hyperglycaemia-associated increase in protein turnover could be normalised during euglycaemia with diet, metformin and sulfonylurea treatment [10]. In this regard, it is noteworthy that decreased aortic DDAH activity correlates positively with elevated plasma ADMA in streptozotocininduced diabetes in rats [49].…”

“…Assays for immunoreactive insulin and glucagon, and glucose-specific activity are described in [10,20]. Plasma total BCAA were measured by a rapid enzymatic, fluorometric assay [16] during the clamp.…”

“…Protein catabolism is increased in uncontrolled diabetes, and is corrected with restoration of normoglycaemia [10]. Furthermore, in states of lesser insulin resistance ± insufficiency, alterations in protein turnover also occur [11][12][13].…”

Nutrition Recommendations and Interventions for Diabetes–2006

“…A number of studies in healthy individuals and in individuals with type 2 diabetes have demonstrated that glucose produced from ingested protein does not increase plasma glucose concentration but does produce increases in serum insulin responses (1,66). Abnormalities in protein metabolism may be caused by insulin deficiency and insulin resistance; however, these are usually corrected with good blood glucose control (67).…”