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NAFLD and interactions with insulin resistance
INSULIN RESISTANCE: SHOULD WE MEASURE IT AND
DOES IT PROMOTE LIVER DISEASE PROGRESSION?
Elisabetta Bugianesi
Department of Medical Sciences,
Division of Gastroenterology,
University of Turin, Italy
E-mail: elisabetta.bugianesi@unito.it
Take home messages
• IS/IR is usually tested on glucose metabolism; several dynamic and static methods have been proposed
for their quantitative assessment.
• The reproducibility of static methods depends largely on analytical variability and day-to-day
variability of insulin concentrations, while this problem is generally overcome in OGTT-derived
formulas.
• There is important evidence that IR promotes the progression of simple steatosis to NASH
and fibrosis. The method used to measure IS/IR is critical to unveil the association between IR,
hyperinsulinemia and liver damage.
• In clinical practice, this translates into the use of indices of IS/IR in the development of several
algorithms for the non-invasive prediction of severe liver damage based on multiple components of
the MetS.
• A better understanding of the complex mechanisms underlying the interaction between IR and liver
damage remains a primary target for the proper management of NAFLD/NASH.
Introduction
NAFLD is a complex condition, ranging from simple steatosis to NASH and cirrhosis. NAFLD
results from the interaction between multiple genes and social, behavioural and environmental factors.
IR represents its pathophysiological hallmark and the common ground of the features of the MetS,
associated with an increased risk of fat accumulation and fibrosis. Insulin signalling, via different
pathways, is involved in metabolic and immune modulations, directly or indirectly affecting liver injury
and the wound-healing response and possibly varying from patient to patient. An increasing number of
features of the MetS, particularly T2DM and obesity, are risk factors for the presence of steatohepatitis
and are important phenotypic reflections of insulin resistance. In clinical practice, this translates into
the use of indices of IS/IR as screening tools to detect IR in NAFLD and in the development of several
algorithms for the non-invasive prediction of severe liver damage based on multiple components of the
MetS. A better understanding of the complex mechanisms underlying the interaction between insulin
resistance and liver damage remains a primary target for the proper management of NAFLD/NASH.
How to measure insulin resistance
IR is typically defined as decreased sensitivity or responsiveness to metabolic actions of insulin, but this
definition does not provide any insight on the type of tissue where insulin activity is measured (muscle,
adipose tissue, hepatocytes, etc.) and on the substrate that is tested (glucose, lipids, proteins, etc.) [1].
From a physiological point of view, discerning the sites of IR is not trivial. IR in the skeletal muscle (or
46 Postgraduate Course Syllabus • Metabolic Liver Disease
INSULIN RESISTANCE: SHOULD WE MEASURE IT AND
DOES IT PROMOTE LIVER DISEASE PROGRESSION?
Elisabetta Bugianesi
Department of Medical Sciences,
Division of Gastroenterology,
University of Turin, Italy
E-mail: elisabetta.bugianesi@unito.it
Take home messages
• IS/IR is usually tested on glucose metabolism; several dynamic and static methods have been proposed
for their quantitative assessment.
• The reproducibility of static methods depends largely on analytical variability and day-to-day
variability of insulin concentrations, while this problem is generally overcome in OGTT-derived
formulas.
• There is important evidence that IR promotes the progression of simple steatosis to NASH
and fibrosis. The method used to measure IS/IR is critical to unveil the association between IR,
hyperinsulinemia and liver damage.
• In clinical practice, this translates into the use of indices of IS/IR in the development of several
algorithms for the non-invasive prediction of severe liver damage based on multiple components of
the MetS.
• A better understanding of the complex mechanisms underlying the interaction between IR and liver
damage remains a primary target for the proper management of NAFLD/NASH.
Introduction
NAFLD is a complex condition, ranging from simple steatosis to NASH and cirrhosis. NAFLD
results from the interaction between multiple genes and social, behavioural and environmental factors.
IR represents its pathophysiological hallmark and the common ground of the features of the MetS,
associated with an increased risk of fat accumulation and fibrosis. Insulin signalling, via different
pathways, is involved in metabolic and immune modulations, directly or indirectly affecting liver injury
and the wound-healing response and possibly varying from patient to patient. An increasing number of
features of the MetS, particularly T2DM and obesity, are risk factors for the presence of steatohepatitis
and are important phenotypic reflections of insulin resistance. In clinical practice, this translates into
the use of indices of IS/IR as screening tools to detect IR in NAFLD and in the development of several
algorithms for the non-invasive prediction of severe liver damage based on multiple components of the
MetS. A better understanding of the complex mechanisms underlying the interaction between insulin
resistance and liver damage remains a primary target for the proper management of NAFLD/NASH.
How to measure insulin resistance
IR is typically defined as decreased sensitivity or responsiveness to metabolic actions of insulin, but this
definition does not provide any insight on the type of tissue where insulin activity is measured (muscle,
adipose tissue, hepatocytes, etc.) and on the substrate that is tested (glucose, lipids, proteins, etc.) [1].
From a physiological point of view, discerning the sites of IR is not trivial. IR in the skeletal muscle (or
46 Postgraduate Course Syllabus • Metabolic Liver Disease
