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

OBJECTIVE - We tested whether oral hypoglycemic agents (OHA), gliclazide with or without metformin, during an isoenergetic (ISO) and then a low-energy diet (LED) improve the altered kinetics of whole-body protein metabolism in type 2 diabetes. RESEARCH DESIGN AND METHODS - A total of 13 type 2 diabetic patients (aged 51 +/- 2 years, weight 110 +/- 5 kg, BMI 41 +/- 1 kg/m(2), fasting glucose [FSG] 11.5 +/- 0.9 mmol/l) (means +/- SEM) and 10 obese control subjects (48 +/- 3 years, 98 +/- 6 kg, 37 +/- 2 kg/m(2), FSG 5.5 +/- 0.3 mmol/l) consumed an ISO, 1.5 g.kg(-1).day(-1) protein for a body weight corresponding to a BMI of 25 (BMI25), a formula diet (7 days for obese control subjects, 15 days for diabetic patients), and then a 28-day LED with 50% of the energy of ISO but the same protein intake (101 +/- 2 g/day). OHAs were given during ISO (days 8-15) and LED. On days 6-8 land 12-14 for diabetic subjects) of ISO and 26-28 of LED, the 60-h oral N-15-glycine method was used to obtain nitrogen flux (Q), synthesis (S), and breakdown (B). Muscle protein catabolism was estimated from N-tau-methylhistidine (3MH) excretion. RESULTS- During ISO with hyperglycemia, Q, and B adjusted for fat-free mass, sex, and age were higher and nitrogen balance and net endogenous protein synthesis (S-B) lower than in control subjects (P < 0.05). OHA decreased FSG (9 +/- 1 mmol/l) and 3MH and increased plasma insulin-to-glucose ratio, nitrogen retention, and S-B to levels in control subjects. The change in S-B correlated with that in FSG (r = -0.845, P = 0.001) and in fasting plasma C-peptide (r = 0.852, P = 0.0005). With LED and OHA, weight decreased 6.3 kg, glycemia reached near-normal levels, and nitrogen equilibrium was maintained; Q decreased by 7%, S and B by 11% (P < 0.05) to values found in control subjects. CONCLUSIONS - OHA during ISO corrected protein turnover in relation to glycemia and plasma C-peptide. The LED maintained protein homeostasis in obese control subjects and, in diabetes patients with OHA, normalized protein metabolism. These findings have implications for diet and OHA prescription.