Examining the Relationship Between Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome in Nondiabetic Subjects

Abstract

The findings here suggest that both NAFLD and the MS very early in development have a common inciting mechanism(s)-most likely IR. Accordingly, the early concurrent temporal results are consistent with the concept that NAFLD is a hepatic manifestation of the IR associated with the MS. They do not exclude the possibility that once some liver functional adjustments take place, several aspects of the MS are bolstered further, perhaps via intensified heightening of IR.

Circulating ALT Levels in Healthy Volunteers Over Life-Span: Assessing Aging Paradox and Nutritional Implications

“…Nevertheless, higher "normal" ALT levels, not so much AST levels, have been associated with greater risk for type 2 diabetes mellitus. Thus, imperative to note concerning the diagnosis of NAFLD, relatively high-normal ALT levels together with other clinical features of the MS should raise strong suspicion (2,22). Strengthening the latter suggestion, one study reported associated signs for MS increased in higher quintiles of the "normal" ALT range compared with lower quintiles (4).…”

“…Numerous aspects of the precise pathogenesis are uncertain, however, IR and central fat accumulation, frequently associated with poor lifestyle choices in diet and exercise, appear to be key components in the pathophysiology (1,10,13). Specifically, visceral fat accumulation favors eventual localization of this element to the liver (1,(20)(21)(22). In addition to augmenting hepatic fat uptake due to the close proximity to the central fat deposits, the associated IR secondary to this phenomenon appears to alter pathways of uptake, synthesis, degradation, and secretion of free fatty acids ultimately favoring even more enhanced accrual of triglycerides in the hepatocytes creating a vicious unhealthful cycle (1,20).…”

“…In addition to augmenting hepatic fat uptake due to the close proximity to the central fat deposits, the associated IR secondary to this phenomenon appears to alter pathways of uptake, synthesis, degradation, and secretion of free fatty acids ultimately favoring even more enhanced accrual of triglycerides in the hepatocytes creating a vicious unhealthful cycle (1,20). Since scores of investigators accept that IR is also the principal driving force behind MS (22)(23)(24), it is not too surprising that hepatic fat infiltration has been connected to various aspects of the syndrome (13,25). As noted above and important not to forget, the pathological processes behind even seemingly benign NAFLD are not infrequently associated with the concomitant presence of multiple components of MS: obesity (47%-90%), diabetes mellitus (28%-55%), hyperlipidemia (4%-92%), and raised blood pressure-all especially harmful to the cardiovascular system (9,(18)(19)(20)23).…”

“…The usual biochemical pattern in NAFLD is increased levels of ALT exceeding those of AST. Thus, the ratio AST/ALT characteristically decreases below one in hepatic steatosis (1,22,29). To add some confusion, appearance of fibrosis and cirrhosis are associated with a ratio > 1 (26).…”

“…Regrettably, current laboratory handling of values not infrequently fail time and time again to convincingly identify the presence of clinically established NAFLD because measurements of aminotransferases (ALT, AST) as well as accompanying elements of the MS are often within their accepted normal limits (< 40 IU/L) (22,26,30). Nevertheless, higher "normal" ALT levels, not so much AST levels, have been associated with greater risk for type 2 diabetes mellitus.…”