Effect of NIDDM on the Kinetics of Whole-Body Protein Metabolism

Abstract

We postulated that dietary protein utilization and body protein metabolism are altered in hyperglycemic individuals with non-insulin-dependent diabetes mellitus (NIDDM). This was tested by estimating the kinetics of protein metabolism in obese NIDDM patients in the hyperglycemic state of isoenergetic feeding and in the normoglycemic state induced by the prolonged use of a very-low-energy diet (VLED) and comparing them with results in obese nondiabetic subjects studied previously. Seven obese subjects with NIDDM (one male, six females, body mass index = 35.8 +/- 2.0 kg/m2) were given a 1.7 MJ (410 kcal) all protein (93 g/day) diet derived from hydrolyzed collagen and supplemented with tryptophan and methionine, which provides 16% of its amino acids as essential, a multivitamin and mineral supplement, and 16 mmol KCl for 42 days. During the seven-day isoenergetic diet and at weeks 4 and 6 of the VLED, amino nitrogen (N) flux rate was calculated from the urine [15N]urea enrichment by using the 60-h oral [15N]glycine method to obtain the integrated feeding-fasting metabolism. Rates of synthesis (S) and breakdown (B) were calculated from N flux. At day 7 of the isoenergetic diet, whole-body N flux, S, B, and resting metabolic rate (RMR) were 12-24% greater (P < 0.05) in the NIDDM subjects than observed in nondiabetic obese subjects. Mean plasma glucose decreased (P < 0.05) from the isoenergetic period (14.9 +/- 2.4 mM) to 7.2 +/- 1.2 mM at week 4 and 6.5 +/- 1.1 mM at week 6 of the VLED. RMR declined progressively by 25% at week 5 of the VLED. Corresponding significant (P < 0.05) decreases from isoenergetic feeding to weeks 4 and 6 of the VLED occurred in whole-body N flux (from 51 +/- 2 to 42 +/- 1 g N/day), in S (from 38 +/- 3 to 24 +/- 1 g N/day), and in B (from 39 +/- 3 to 26 +/- 1 g N/day) resulting in net losses (S-B). S-B was significantly more negative (P < 0.05) in NIDDM than in the nondiabetic obese subjects at week 4 (-1.5 +/- 0.5 vs. 0.9 +/- 0.3 g N/day) but not at week 6 (-1.3 +/- 0.4 vs. -0.9 +/- 4 g N/day). During the VLED, N balance became less negative with time but never reached equilibrium in NIDDM. Thus, abnormal protein metabolism is present in NIDDM in the isoenergetic fed state with moderate hyperglycemia and persists during a VLED that restores glycemia to near normal.

Use of the insulin pump in treat cystic fibrosis related diabetes

“…Previous studies in CF have demonstrated increased protein catabolism [14,15] and studies by our group [16] and others [17,18] have described resistance to insulin's anti-catabolic effect on protein breakdown (i.e. they need more insulin to suppress protein catabolism than a non-CF person, yet they are insulin deficient) [2].…”

Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes

“…Several studies have shown increased urinary N loss and net whole-body protein loss in type 2 diabetic patients, even those who are hyperinsulinemic (Gougeon et al 1994(Gougeon et al , 1997(Gougeon et al , 1998. Halvatsiotis et al (2002) found no difference in plasma amino acid concentrations between type 2 diabetic patients from whom insulin treatment was withdrawn transiently and patients who were given intensive insulin treatment for 11 days, except for a reduction in the glycine levels in the untreated patients.…”

Protein and diabetes: Much advice, little research

“…In moderately hyperglycemic obese subjects with type 2 diabetes compared with an obese control group, Gougeon et al [7] reported that during a weight-maintaining diet with ample protein intake, protein metabolism is accelerated. In contrast to subjects without diabetes, euglycemia from a very low-energy diet did not completely re-establish nitrogen equilibrium in subjects with type 2 diabetes.…”

“…Fortunately, the large amount of protein in the customary diet of persons with diabetes compensates for the increased protein catabolism, and thus protects them from protein malnutrition [7].…”

“…These alterations were only corrected with euglycemia from exogenous insulin. This suggests that persons with type 2 diabetes have an altered adaptive mechanism for protein sparing, independent of protein quality [2,7].…”