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[19]
were required to diagnose MetS . Interestingly, concerning dyslipidemia and specifically increased fasting
triglyceride and reduced high-density cholesterol concentration, almost twenty years before, in 1990,
[20]
Austin et al. had published the concept of the atherogenic lipoprotein phenotype as an important CVD
risk factor that was unrelated to low-density lipoprotein cholesterol (LDL-C) concentrations. These authors
described two distinct cardiovascular phenotypes. One of these phenotypes with a preponderance of
atherogenic small dense LDL particles, was associated with increases in plasma levels of triglycerides and
apolipoprotein B, with increased very low and intermediate density lipoproteins. Austin et al. proposed that
[20]
this results in an "atherogenic lipoprotein phenotype" that is now realized to be a key component of MetS-
related dyslipidemia and that may, in large part, be a mediator of the increased CVD risk associated with
both MetS and NAFLD . In support of this notion, there is also considerable evidence that apolipoprotein
[21]
[22]
B-containing lipoproteins are particularly atherogenic .
In the last decade, there has been further awareness that fatty liver, now termed steatotic liver disease,
usually occurs with some metabolic dysfunction, giving rise to MetS features. That awareness that metabolic
dysfunction underpins much of NAFLD prompted the proposal by Eslam et al. that NAFLD should be
[23]
reclassified as metabolic dysfunction-associated fatty liver disease (MAFLD) . The proposed criteria for
diagnosing MAFLD are based on evidence of hepatic steatosis, in addition to one of the following three
metabolic abnormalities: overweight/obesity, presence of T2DM, or evidence of metabolic dysregulation. In
2023, a modified Delphi process that was led by three large pan-national liver associations was set up to try
[24]
and achieve a consensus regarding the name and classification of NAFLD/MAFLD . Steatotic liver disease
(SLD) was chosen as the term to encompass the various aetiologies of hepatic steatosis. The term
steatohepatitis was considered an important pathophysiological concept that should be retained. Thus, the
name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD).
Importantly, with regard to the MetS components, the MASLD definition was to include the presence of at
[19]
least one of five of the classical MetS risk factors proposed by Alberti et al. in 2009 . Additionally, MetALD
was selected to describe subjects with MASLD who consume greater amounts of alcohol per week
[24]
(140-350 g/week and 210-420 g/week for women and men, respectively .
So, in 2024, reflecting on this background, how have these developments created clarity for patients,
clinicians, researchers, and policy-makers dealing with NAFLD? Will this create clarity, or will it generate
further confusion, particularly among non-specialists who have lived with and grown used to diagnosing
NAFLD, with all its recognized inherent flaws? In considering the potential for further confusion,
Endocrinologists/Diabetologists will remember the acrimony that overwhelmed reasoned discussion about
the utility of MetS definition in the first decade of the millennium. The 2009 MetS guideline - discussed
[19]
above emphasized that there should be no obligatory component, but that waist measurement would
continue to be a useful initial screening tool. Three out of five MetS components would qualify a person for
a diagnosis of MetS. All components, except waist circumference, (where ethnic-specific cut-offs would
[19]
apply), would have a single threshold . However, the irony is that despite MetS being important for T2DM
and the title of the paper emphasizing harmony between the different organizations that signed up to it, the
concept of MetS gained little traction and created animosity among those of us working in Diabetology/
Endocrinology. Despite MetS being a strong risk factor for T2DM and also a significant risk factor for CVD
and all-cause mortality in patients with established T2DM , the two key Scientific organizations
[18]
representing patients and professionals interested in T2DM care and research, i.e., the American Diabetes
Association (ADA) and the European Association of the Study of Diabetes (EASD), refused to endorse the
MetS criteria.