Prior to the advent of nuclear magnetic resonance (NMR) spectroscopy, human
glucose metabolism was studied through tracer and tissue biopsy methodolog
y. NMR spectroscopy now provides a noninvasive means to monitor metabolic f
lux and intracellular metabolite concentrations continuously. C-13 NMR spec
troscopy has shown that muscle glycogen synthesis accounts for the majority
of insulin-stimulated muscle glucose uptake in normal volunteers and that
defects in this process are chiefly responsible for insulin resistance in t
ype 1 and type 2 diabetes mellitus, as well as in other insulin resistant s
tates (obesity, insulin-resistant offspring of type 2 diabetic parents, ele
vation of plasma FFA concentrations). Furthermore, using P-31 NMR spectrosc
opy to measure intracellular glucose-6-phosphate, it has been shown that de
fects in insulin-stimulated glucose transport/phosphorylation activity are
primarily responsible for the insulin resistance in these states.