Effect of glutamine on glucose metabolism in children with Duchenne muscular dystrophy.

BACKGROUND & AIMS: Glutamine is a potent gluconeogenic precursor and stimulates insulin secretion. Glutamine's effect on glucose metabolism in Duchenne muscular dystrophy (DMD) has never been studied. To determine plasma glucose and insulin concentrations measured during and after glutamine administration in DMD boys. We hypothesized that glutamine can modulate whole body glutamine-glucose metabolism in DMD, a genetically determined disease.

METHODS

As secondary endpoints of a randomized crossover trial in 30 prepubertal DMD boys, we measured fasting blood glucose, insulin and the Homeostasis Model Assessment (HOMA) index after daily oral glutamine (0.5 g kg(-1) d(-1)) for 4 months versus placebo. In a separate time series trial in 6 prepubertal DMD boys, we measured the same endpoints as well as plasma glutamine and whole body glucose turnover (Ra,glc) (primed continuous i.v. infusion of d-[6,6-(2)D]glucose), while participants received acute oral glutamine (0.5 g kg(-1) d(-1)) continuously for 5 h.

RESULTS

In the randomized trial, baseline measurements of HOMA correlated with age (r = 0,51, p = 0.007) and percent fat estimated by bioelectrical impedance analysis (BIA) (r = 0.39, p = 0.047). After 4 months glutamine supplementation, we observed no treatment or order effect on HOMA or insulin. During acute glutamine for 5 h (time series trial), plasma glutamine doubled and was associated with increased plasma insulin concentration (10.42 ± 2.54 vs 7.32 ± 1.86, p = 0.05) with no effect on plasma glucose, HOMA or Ra,glc.

CONCLUSIONS

Acute glutamine transiently stimulates insulin secretion in DMD boys, which could be mediated by plasma glutamine concentrations. Fasting insulin concentration and HOMA might provide quantifiable indices of disease progression.