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Neuroadrenergic Dysfunction Along the Diabetes Continuum
- Source :
- Diabetes
- Publication Year :
- 2012
- Publisher :
- American Diabetes Association, 2012.
-
Abstract
- Neuroadrenergic function in type 2 diabetic (T2D) patients without neuropathy is poorly characterized. We therefore compared sympathetic nervous system activity at rest and during an oral glucose tolerance test in obese metabolic syndrome (MetS) subjects classified as glucose intolerant (impaired glucose tolerance [IGT]; n = 17) or treatment-naive T2D (n = 17). Untreated subjects, matched for age (mean 59 ± 1 year), sex, BMI (32.4 ± 0.6 kg/m2), and family history of diabetes were studied. We measured resting muscle sympathetic nerve activity (MSNA) by microneurography, whole-body norepinephrine kinetics by isotope dilution, insulin sensitivity by euglycemic-hyperinsulinemic clamp (steady-state glucose utilization adjusted for fat-free mass and steady-state insulin concentration [M/I]), and MetS components. T2D subjects had higher resting MSNA burst incidence (67 ± 4 versus 55 ± 3 bursts per 100 heartbeats; P = 0.05) and arterial norepinephrine levels (264 ± 33 versus 167 ± 16 pg/mL; P = 0.02), lower plasma norepinephrine clearance (by 17%; P = 0.03), and reduced neuronal reuptake compared with IGT subjects (by 46%; P = 0.04). Moreover, norepinephrine spillover responses to glucose ingestion were blunted in T2D subjects. The M/I value independently predicted whole-body norepinephrine spillover (r = −0.47; P = 0.008), whereas fasting insulin level related to neuronal norepinephrine reuptake (r = −0.35, P = 0.047). These findings demonstrate that progression to T2D is associated with increased central sympathetic drive, blunted sympathetic responsiveness, and altered norepinephrine disposition.
- Subjects :
- medicine.medical_specialty
Sympathetic nervous system
business.industry
Endocrinology, Diabetes and Metabolism
Insulin
medicine.medical_treatment
Microneurography
medicine.disease
Norepinephrine (medication)
Impaired glucose tolerance
Endocrinology
Insulin resistance
medicine.anatomical_structure
Diabetes mellitus
Internal medicine
Internal Medicine
medicine
Metabolic syndrome
business
Obesity Studies
medicine.drug
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....a957184d1f95f85e8628f6690a42bf05