Neuroadrenergic Dysfunction Along the Diabetes Continuum: A Comparative Study in Obese Metabolic Syndrome Subjects

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 10; pp. 2506 - 2516
• Main Authors: STRAZRUCKY, Nora E, GRIMA, Mariee T, SCHLAICH, Markus P, LAMBERT, Gavin W, SARI, Carolina I, EIKELIS, Nina, LAMBERT, Elisabeth A, NESTEL, Paul J, ESLER, Murray D, DIXON, John B, CHOPRA, Reena, TILBROOK, Alan J
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.2012
• Subjects: Biological and medical sciences; Blood Glucose - metabolism; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Diagnosis; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exercise; Family medical history; Female; Glucose; Glucose Intolerance - complications; Glucose Intolerance - metabolism; Glucose Intolerance - physiopathology; Glucose tolerance test; Glucose tolerance tests; Heart rate; Humans; Hypertension; Insulin resistance; Insulin Resistance - physiology; Male; Medical sciences; Metabolic diseases; Metabolic syndrome; Metabolic Syndrome - complications; Metabolic Syndrome - metabolism; Metabolic Syndrome - physiopathology; Middle Aged; Miscellaneous; Nervous system; Nervous system, Sympathetic; Norepinephrine - metabolism; Obesity; Obesity - complications; Obesity - metabolism; Obesity - physiopathology; Obesity Studies; Other metabolic disorders; Physical fitness; Physiological aspects; Plasma; Sympathetic Nervous System; Type 2 diabetes; Australia; Endocrinopathy; Human; Obesity; Dysfunction; Diabetes mellitus; Nutrition disorder; Metabolic diseases; Cardiovascular disease; Metabolic syndrome; Nutritional status; Comparative study
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db12-0138

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.