title: Comparable Attenuation of Sympathetic Nervous System Activity in Obese Subjects with Normal Glucose Tolerance, Impaired Glucose Tolerance, and Treatment Naïve Type 2 Diabetes following Equivalent Weight Loss.
abstract: Background and Purpose:Elevated sympathetic nervous system (SNS) activity is a characteristic of obesity and type 2 diabetes (T2D) that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss.Methods:Un-medicated obese individuals categorized as normal glucose tolerant (NGT,n= 15), impaired glucose tolerant (IGT,n= 24), and newly-diagnosed T2D (n= 15) consumed a hypocaloric diet (29% fat, 23% protein, 45% carbohydrate) for 4-months. The three groups were matched for baseline age (56 ± 1 years), body mass index (BMI, 32.9 ± 0.7 kg/m2), and gender. Clinical measurements included whole-body norepinephrine kinetics, muscle sympathetic nerve activity (MSNA, by microneurography), spontaneous cardiac baroreflex sensitivity (BRS), and oral glucose tolerance test.Results:Weight loss averaged -7.5 ± 0.8, -8.1 ± 0.5, and -8.0 ± 0.9% of body weight in NGT, IGT, and T2D groups, respectively. T2D subjects had significantly greater reductions in fasting glucose, 2-h glucose and glucose area under the curve (AUC0-120) compared to NGT and IGT (group effect,P<0.001). Insulinogenic index decreased in IGT and NGT groups and increased in T2D (group × time,P= 0.04). The magnitude of reduction in MSNA (-7 ± 3, -8 ± 4, -15 ± 4 burst/100 hb, respectively) and whole-body norepinephrine spillover rate (-28 ± 8, -18 ± 6, and -25 ± 7%, respectively), time effect bothP<0.001, did not differ between groups. After adjustment for age and change in body weight, Δ insulin AUC0-120was independently associated with reduction in arterial norepinephrine concentration, whilst Δ LDL-cholesterol and improvement in BRS were independently associated with decrease in MSNA.Conclusions:Equivalent weight loss through hypocaloric diet is accompanied by similar sympathoinhibition in matched obese subjects with different baseline glucose tolerance. Attenuation of hyperinsulinemia and hyperlipidemia, rather than glycemic indices, is associated with reduction in SNS activity following weight loss intervention.
authors.affiliation: Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia.
authors.forename: Nora E
authors.initials: NE
authors.lastname: Straznicky
authors.affiliation: Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia.
authors.forename: Mariee T
authors.initials: MT
authors.lastname: Grima
authors.affiliation: Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia.
authors.forename: Carolina I
authors.initials: CI
authors.lastname: Sari
authors.affiliation: Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes InstituteMelbourne, VIC, Australia; Department of Physiology, Monash UniversityMelbourne, VIC, Australia; Department of Physiology, University of MelbourneMelbourne, VIC, Australia.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Lambert
authors.affiliation: Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Phillips
authors.affiliation: Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia.
authors.forename: Nina
authors.initials: N
authors.lastname: Eikelis
authors.affiliation: Heart Failure Research Group, Baker IDI Heart and Diabetes InstituteMelbourne, VIC, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash UniversityMelbourne, VIC, Australia.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Mariani
authors.affiliation: Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Hering
authors.affiliation: Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes InstituteMelbourne, VIC, Australia; Department of Primary Health Care, Monash UniversityMelbourne, VIC, Australia.
authors.forename: John B
authors.initials: JB
authors.lastname: Dixon
authors.affiliation: Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes InstituteMelbourne, VIC, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash UniversityMelbourne, VIC, Australia.
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Lambert
keywords: glucose tolerance; hyperinsulinemia; hypocaloric diet; obesity; sympathetic nervous system; type 2 diabetes; weight loss