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 both P <0.001, did not differ between groups. After adjustment for age and change in body weight, Δ insulin AUC0−120 was 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.
Highlights
The high prevalence of obesity, estimated to exceed 25% in many developed countries including Australia (Australian Bureau of Statistics, 2015), is a serious public-health concern that confers excess mortality and morbidity due to its associations with chronic conditions such as type 2 diabetes (T2D) and cardiovascular disease (Prospective Studies Collaboration, 2009)
In accordance with the categorization, T2D subjects had higher fasting glucose, 2-h glucose, glucose AUC0−120 and homeostasis model assessment of insulin resistance (HOMA-IR) and lower insulinogenic index compared to normal glucose tolerant (NGT) and impaired glucose tolerant (IGT) groups
The insulin response to OGTT was greatest in the NGT, albeit differences between groups did not reach statistical significance (P = 0.12)
Summary
The high prevalence of obesity, estimated to exceed 25% in many developed countries including Australia (Australian Bureau of Statistics, 2015), is a serious public-health concern that confers excess mortality and morbidity due to its associations with chronic conditions such as type 2 diabetes (T2D) and cardiovascular disease (Prospective Studies Collaboration, 2009). An early viewpoint, based on experimental hypothalamic models of obesity, clinical studies of venous and urinary norepinephrine concentration, and studies in Pima Indians (an ethnic population with low SNS activity) was that SNS underactivity was the basis of weight gain and the development obesity (Bray, 1990; Tataranni et al, 1997; Snitker et al, 2000). This was congruent with the known importance of the SNS in all aspects of daily energy expenditure. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss
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