OBJECTIVE - We tested whether oral hypoglycemic agents (OHA), gliclazide wi
th or without metformin, during an isoenergetic (ISO) and then a low-energy
diet (LED) improve the altered kinetics of whole-body protein metabolism i
n 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 (4
8 +/- 3 years, 98 +/- 6 kg, 37 +/- 2 kg/m(2), FSG 5.5 +/- 0.3 mmol/l) consu
med 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 durin
g 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 catabo
lism 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 FS
G (9 +/- 1 mmol/l) and 3MH and increased plasma insulin-to-glucose ratio, n
itrogen 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 k
g, glycemia reached near-normal levels, and nitrogen equilibrium was mainta
ined; Q decreased by 7%, S and B by 11% (P < 0.05) to values found in contr
ol subjects.
CONCLUSIONS - OHA during ISO corrected protein turnover in relation to glyc
emia and plasma C-peptide. The LED maintained protein homeostasis in obese
control subjects and, in diabetes patients with OHA, normalized protein met
abolism. These findings have implications for diet and OHA prescription.