Blunted sympathetic neural response to oral glucose in obese subjects with the insulin-resistant metabolic syndrome.
BACKGROUND
Glucose ingestion stimulates sympathetic nervous system (SNS) activity in lean subjects, whereas blunted responses have been reported in the obese.


OBJECTIVE
The objective was to investigate the impact of insulin resistance on the SNS response to oral glucose.


METHODS
Nineteen insulin-resistant (IR) and 12 insulin-sensitive (IS) obese subjects with the metabolic syndrome and matched for age, sex, and blood pressure participated. Simultaneous measurements of muscle sympathetic nerve activity (MSNA) by microneurography, whole-body norepinephrine spillover rate, cardiac baroreflex sensitivity (BRS), calf blood flow, and arterial blood pressure were made at baseline and 30, 60, 90, and 120 min after a 75-g glucose load.


RESULTS
IR subjects had a higher insulin area under the curve from 0 to 120 min (AUC(0-120): 13,468 +/- 677 compared with 6399 +/- 612 mU/L . min; P < 0.001), glucose AUC(0-120) (P < 0.05), and resting MSNA (41 +/- 3 compared with 31 +/- 3 bursts/min; P = 0.03) than did IS subjects. MSNA and the norepinephrine spillover rate increased from baseline (by 29 +/- 7% and 40 +/- 13%, respectively; P < or = 0.001 for both) in IS subjects after the glucose load. In contrast, there was a blunted and delayed sympathetic response in IR subjects. Cardiac BRS and diastolic blood pressure decreased, whereas calf blood flow increased after the glucose load and by a similar magnitude in both groups (P < 0.01). Body mass index, abdominal fat, and insulin AUC(0-120) were independent (inverse) predictors of the SNS response.


CONCLUSIONS
IR subjects with the metabolic syndrome have a blunted SNS response to oral glucose compared with IS subjects with the metabolic syndrome, which is related to central adiposity and the insulin response but not to differences in skeletal muscle vasodilation or BRS.
Straznicky
Nora E
NE
Human Neurotransmitters and Heart Failure Division, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia. nora.straznicky@bakeridi.edu.au
Lambert
Gavin W
GW
Masuo
Kazuko
K
Dawood
Tye
T
Eikelis
Nina
N
Nestel
Paul J
PJ
McGrane
Mariee T
MT
Mariani
Justin A
JA
Socratous
Florentia
F
Chopra
Reena
R
Esler
Murray D
MD
Schlaich
Markus P
MP
Lambert
Elisabeth A
EA
D019540:Area Under Curve; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007866:Leg / Q000098:blood supply / Q000294:innervation; D008297:Male; D008657:Metabolic Clearance Rate; D024821:Metabolic Syndrome / Q000097:blood / Q000503:physiopathology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000294:innervation*; D009638:Norepinephrine / Q000378:metabolism / Q000493:pharmacokinetics; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D012039:Regional Blood Flow / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose; D009638:Norepinephrine