Role of hyperglucagonemia in catabolism associated with type 1 diabetes: effects on leucine metabolism and the resting metabolic rate.
Level 3 - non-randomized controlled study
Controlled experimental crossover study in humans without reported randomization.
PubMed 9792544 · doi:10.2337/diabetes.47.11.1748
What was done
Twelve individuals with type 1 diabetes were studied across five experimental protocols: insulin treatment, insulin deprivation alone, insulin deprivation with somatostatin to suppress endogenous glucagon plus growth hormone replacement, insulin deprivation with somatostatin without growth hormone replacement, and insulin deprivation with somatostatin plus high-level glucagon replacement. Energy expenditure was measured using indirect calorimetry, and protein metabolism was assessed using L-[1-(13)C,15N]leucine and L-[1-(13)C]leucine tracers.
What was found
Leucine oxidation and the resting metabolic rate were significantly lower during insulin treatment and during insulin deprivation with somatostatin-induced glucagon suppression compared with insulin deprivation alone. High-level glucagon replacement during somatostatin infusion in the insulin-deprived state increased leucine oxidation and resting metabolic rate. In multiple regression analysis, leucine oxidation (R2 = 0.79) and resting metabolic rate (R2 = 0.81) correlated with glucagon levels and not with other hormones. Hyperglucagonemia did not affect leucine transamination and showed only a trend toward decreased protein synthesis. Insulin replacement decreased leucine flux and oxidation. Exact numerical values were not reported in the abstract.
Why it matters
The findings show that while insulin deficiency increases protein breakdown, hyperglucagonemia directly drives the elevated leucine oxidation and resting metabolic rate seen in insulin deprivation.
Limits
The sample size was small at 12 participants. The abstract does not state whether the protocol sequence was randomized. Exact baseline characteristics, hormone concentrations, and metabolic rates with variance measures were omitted from the abstract.
Cited by
- supports A study by Nair and colleagues demonstrated that insulin administration in type 1 diabetes begins to reduce the elevated metabolic rate within minutes.