Effects of Pioglitazone Treatment on Sympathetic Nervous System Function in Metabolic Syndrome Obesity

Effects of Pioglitazone Treatment on Sympathetic Nervous System Function in Metabolic Syndrome Obesity

Mechanisms of Sympathetic Overactivity in the Metabolic Syndrome: Effects of Reversing Insulin Resistance by Drug Treatment

An abdominal distribution of fat is associated with the greatest heart disease risk, because commonly, several risk factors of metabolic origin cluster in these individuals. When this occurs the condition is called the 'metabolic syndrome'. Increased activity of the sympathetic nervous system resulting in enhanced release of the stress hormone 'noradrenaline', may be one mechanism by which adverse cardiovascular and metabolic sequela of the metabolic syndrome might be mediated. Impaired insulin action may be one factor contributing to increased noradrenaline release. The aim of this Study is to determine whether treatment with a drug called pioglitazone which is known to improve insulin action, results in reduced sympathetic nervous system activity and stress hormone release when compared to treatment with a dummy drug (placebo).

The rapidly growing burden of obesity together with a population that is becoming older raises the importance of effective strategies for the primary prevention and treatment of the metabolic syndrome in order to combat the epidemic of type 2 diabetes and to reduce the increased risk of cardiovascular mortality. Increased sympathetic nervous system activity may participate in the pathogenesis and complications of the metabolic syndrome. This Study will use a randomised controlled design to evaluate the effects of pioglitazone treatment on sympathetic activity in middle-aged subjects with the metabolic syndrome.The results will generate new information on the neuroadrenergic effects of thiazolidinediones in this clinical setting. This is relevant to the understanding of the pathophysiology of the metabolic syndrome and to its clinical management.

Sympathetic nervous system activity, measured as muscle sympathetic nervous activity and whole-body noradrenaline spillover

Inclusion Criteria: Males and females aged 45-65 years, non-smokers, HOMA index > 2.5 and who meet ATP III criteria for the metabolic syndrome Exclusion Criteria: History of diabetes, previous MI, stroke, heart failure, impaired hepatic or renal function. Inability to cease medications which may affect study parameters.

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Straznicky NE, Grima MT, Sari CI, Lambert EA, Phillips SE, Eikelis N, Kobayashi D, Hering D, Mariani JA, Dixon JB, Nestel PJ, Karapanagiotidis S, Schlaich MP, Lambert GW. Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss. Cardiovasc Diabetol. 2015 Aug 22;14:113. doi: 10.1186/s12933-015-0276-2.

Straznicky NE, Grima MT, Sari CI, Eikelis N, Lambert GW, Nestel PJ, Richards K, Dixon JB, Schlaich MP, Lambert EA. Pioglitazone treatment enhances the sympathetic nervous system response to oral carbohydrate load in obese individuals with metabolic syndrome. Metabolism. 2015 Jul;64(7):797-803. doi: 10.1016/j.metabol.2015.03.006. Epub 2015 Mar 18.

Straznicky NE, Grima MT, Lambert EA, Sari CI, Eikelis N, Nestel PJ, Phillips SE, Hering D, Karapanagiotidis S, Dixon JB, Schlaich MP, Lambert GW. Arterial norepinephrine concentration is inversely and independently associated with insulin clearance in obese individuals with metabolic syndrome. J Clin Endocrinol Metab. 2015 Apr;100(4):1544-50. doi: 10.1210/jc.2014-3796. Epub 2015 Jan 15.

Straznicky NE, Grima MT, Sari CI, Eikelis N, Lambert GW, Nestel PJ, Karapanagiotidis S, Wong C, Richards K, Marusic P, Dixon JB, Schlaich MP, Lambert EA. A randomized controlled trial of the effects of pioglitazone treatment on sympathetic nervous system activity and cardiovascular function in obese subjects with metabolic syndrome. J Clin Endocrinol Metab. 2014 Sep;99(9):E1701-7. doi: 10.1210/jc.2014-1976. Epub 2014 Jun 17.