Diabetes and Protein Metabolism

The celebrated Greek physician Aretaeus the Cappadocian some 1900 years ago described diabetes as a condition with “a melting down of the flesh and limbs into urine.” Remarkably, his observations are amazingly durable and accurate even by the standards of today with reference to type 1 diabetes. For example, insulin deprivation in type 1 diabetic patients causes a profound increase in catabolism, especially in skeletal muscle (1–4). Moreover, this net muscle protein catabolism is due to a net increase in protein breakdown rather than a decline in protein synthesis (1–4). In contrast, despite substantial alterations in glucose and lipid metabolism, the effect of type 2 diabetes on changes in protein metabolism is at best subtle, and results are inconsistent (5–8). A key difference is that in type 1 diabetic patients on insulin deprivation, muscle mass withers away (as demonstrated by profound cachexia in type 1 diabetic patients during the preinsulin era), whereas no such dramatic changes occur in type 2 diabetic patients with poor glycemic control. Withdrawal of treatment for 10 days in type 2 diabetic patients had little effect on amino acid levels or protein metabolism (8), although glucose metabolism is substantially altered; this may relate to differences in portal …