Reply:

Abstract

We thank Drs. Dogru and Teoman for their interesting comments regarding our recent article on the importance of visceral fat to the pathogenesis of nonalcoholic steatohepatitis.1 Our study showed visceral fat to be a key mediator of steatohepatitis independent of insulin resistance and importantly, independent of a diagnosis of metabolic syndrome (MetS). We agree that all components of the MetS can variably be associated with both insulin levels and those of circulating adipokines. However, the MetS (as defined by various criteria) has been developed purely for operational reasons. This syndrome is the consequence, rather than the cause of metabolic dysregulation. For this reason, in our multivariate analysis, we controlled the effects of visceral fat for both circulating adipokines and insulin sensitivity as measured by the homeostasis model assessment of insulin resistance (HOMA-IR). The HOMA-IR has been shown to correlate well with the results of the euglycemic-hyperinsulinemic clamp in patients with and without type 2 diabetes, even in the presence of metformin or sulfonylureas.2, 3 Thus, any confounding effect of MetS components, or indeed the medications used to treat these components, will have been reflected and controlled for by HOMA-IR levels and those of the circulating adipokines. We are happy to provide some additional results that clarify the relationship between visceral fat and the other components of the MetS (Table 1). These demonstrate that the most marked changes in visceral fat occur with increasing dysregulation of glucose handling, while those associated with dyslipidemia and hypertension did not reach statistical significance. When the association between these individual metabolic variables and necroinflammation and fibrosis in nonalcoholic steatohepatitis was considered, only MetS glucose (P = 0.04) was significant, while elevated blood pressure (P = 0.35), elevated triglycerides (P = 0.9), and low high-density lipoprotein (P = 0. 13) were not associated. Given that we have already specifically controlled for the effects of insulin sensitivity, we did not further analyze the data. David van der Poorten*, Jacob George*, * Storr Liver Unit, Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.