Diabetes. 2012 Oct;61(10):2506-16. Epub 2012 Jun 4.
Neuroadrenergic dysfunction along the diabetes continuum: a comparative study in obese metabolic syndrome subjects.
Straznicky NE, Grima MT, Sari CI, Eikelis N, Lambert EA, Nestel PJ, Esler MD, Dixon JB, Chopra R, Tilbrook AJ, Schlaich MP, Lambert GW.
Laboratory of Human Neurotransmitters, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia. email@example.com
Comment on: Straznicky et al. neuroadrenergic dysfunction along the diabetes continuum: a comparative study in obese metabolic syndrome subjects. Diabetes 2012;61:2506-2516. [Diabetes. 2013]
Comment on: Straznicky et al. neuroadrenergic dysfunction along the diabetes continuum: a comparative study in obese metabolic syndrome subjects. Diabetes 2012;61:2506-2516.Frontoni S. Diabetes. 2013 Jan; 62(1):e1.
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/m(2)), 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.
PMID: 22664956 [PubMed – indexed for MEDLINE]