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.


METHODS
A total of 13 type 2 diabetic patients (aged 51+/-2 years, weight 110+/-5 kg, BMI 41+/-1 kg/m2, 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/m2, FSG 5.5+/-0.3 mmol/l) consumed an ISO, 1.5 g x kg(-1) x 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 (and 12-14 for diabetic subjects) of ISO and 26-28 of LED, the 60-h oral 15N-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.
Gougeon
R
R
McGill Nutrition and Food Science Center, Royal Victoria Hospital, Montréal, Québec, Canada. rgougeon@rvhmed.lan.mcgill.ca
Styhler
K
K
Morais
J A
JA
Jones
P J
PJ
Marliss
E B
EB
D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism*; D003927:Diet, Diabetic; D004359:Drug Therapy, Combination; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005907:Gliclazide / Q000627:therapeutic use*; D006029:Glycosuria; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D014508:Urea / Q000097:blood; D015431:Weight Loss
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D011506:Proteins; D014508:Urea; D008687:Metformin; D005907:Gliclazide