Fetal growth and insulin resistance in adult life: role of skeletal muscle morphology.
1. Thinness at birth is associated with insulin resistance in adult life and an apparent delay in activation of glycolysis/glycogenolysis in exercising skeletal muscle. As developmental abnormalities of skeletal muscle histology or metabolism may explain this association we examined muscle histology, biochemistry and blood flow in a group of 27 adult women whose birth details were known. 2. Subjects were examined by near-infrared spectroscopy to determine forearm muscle oxygen supply, and by muscle biopsy and forearm plethysmography. Those with a ponderal index at birth < 23 kg/m3 were insulin resistant (assessed by the short insulin-tolerance test-mean rate constants for glucose disappearance = 4.14 compared with 4.83%/min, P = 0.045) and had significantly more rapid muscle reoxygenation than the remainder of the subjects (13 compared with 22 s, P = 0.004). 3. Thinness at birth did not influence muscle capillary density, muscle glycogen content, glycogen synthase activity, citrate synthase activity or resting forearm blood flow. 4. Insulin resistance seen after fetal malnutrition was not associated with abnormal muscle histology, resting muscle blood flow, mitochondrial volume or glycogen content. 5. The increase in muscle reoxygenation rate in adult subjects who were thin at birth could occur to promote oxidative ATP synthesis in compensation for the delay in activation of glycolysis/glycogenolysis. It suggests altered regulation rather than structure of the muscle microcirculation. These changes appear to antedate the structural and biochemical changes seen in muscle from patients with established diabetes.
Thompson
C H
CH
MRC Biochemical and Clinical Magnetic Resonance Unit, John Radcliffe Hospital, Oxford, U.K.
Sanderson
A L
AL
Sandeman
D
D
Stein
C
C
Borthwick
A
A
Radda
G K
GK
Phillips
D I
DI
D005314:Embryonic and Fetal Development; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism; D010991:Plethysmography; D012039:Regional Blood Flow; D019265:Spectroscopy, Near-Infrared
D010100:Oxygen