Accelerated whole-body protein catabolism in subjects with type 2 Diabetes Mellitus and albuminuria

Abstract

Background Albuminuria develops in ~40% of subjects with Type 2 Diabetes Mellitus (T2DM), and is often associated with malnutrition, severe comorbidities and decreased life expectancy. The association between albuminuria and altered whole body protein turnover in T2DM is currently unknown. Objective To assess whole body protein degradation and synthesis in type 2 diabetes with and without albuminuria. Methods Fourteen T2DM male subjects, with either increased [AER+] or normal [AER-] urinary albumin excretion rate, and eleven age-matched male healthy controls, were infused with phenylalanine [Phe] and tyrosine [Tyr] tracers. Post-absorptive rates of appearance (Ra) of Phe (= protein degradation) and Tyr, Phe hydroxylation to Tyr (Hy) (catabolic pathway), and Phe disposal to protein synthesis [PS], were determined. Results Phe and Tyr Ra were not different among the groups. However, in T2DM [AER+], the fraction of Phe disposal to hydroxylation was ~50% and ~25% greater than that of both controls and T2DM [AER-] (p<0.006 and p = 0.17, respectively). Conversely, as compared to controls, the fractional Phe disposal to PS was ~10% lower in T2DM [AER+] (p<0.006), and not different from that in T2DM [AER-]. As a consequence, in T2DM [AER+], the ratio between the fractional Phe disposal to hydroxylation and that to PS was ~70% greater (p = 0.005) than that in healthy controls, whereas in the T2DM [AER-] this ratio was ~30% greater than in controls (p = 0.19). Conclusions On the basis of the kinetics of the essential amino acid phenylalanine, T2DM subjects with increased AER exhibit a catabolic pattern of whole body protein turnover.