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However, this issue is still not completely resolved. Serious concerns exist about the possible synergism
between metabolic factors and alcohol in increasing the risk of HCC [5].Another important consideration
is that alcohol consumption may worsen both hypertriglyceridemia and hyperuricemia, which may be
a concern in patients with NAFLD. Comparative analysis of guidelines has led to the conclusion that
heavy alcohol consumption should be discouraged; meanwhile light to moderate alcohol consumption
may have favourable effects on lipid metabolism and, perhaps, on liver outcomes. However, in the
absence of randomized controlled trials, all guidelines advise against prescribing low to moderate alcohol
consumption as a preventative / therapeutic strategy for NAFLD [6].
Alcohol and T2DM
Alcohol consumption has always been considered a risk factor for the development of T2DM. However,
recent findings suggest that moderate alcohol intake might actually be associated with reduced incidence
of T2DM and its vascular complications. A meta-analysis of 15 studies on 369,862 patients, followed
up for an average of 12 years, concluded that subjects who consumed 6-48 g/day of ethanol exhibited
a 30% reduced risk of T2DM as compared with teetotallers or consumers of >48 g/day. This effect is
independent of either sex or BMI, although a lower incidence of T2DM was observed in women with
a moderate alcohol intake compared with abstainers [7]. There is some evidence that moderate alcohol
intake also protects against T2DM development in men [8]. Indeed, consumption of 1-3 alcoholic
drinks/day was inversely related to T2DM risk (HR 0.80, 95%CI 0.67-0.94) among middle-aged
and elderly Chinese men [9]. Several studies suggest that the beneficial effect of alcohol on T2DM
development may be at least in part mediated by body fat distribution in the European population [10].
Current guidelines specific to diabetic patients are rather cautious because of the calories and body-
weight issues, as well as some untoward metabolic and vascular effects of alcohol. In brief, such guidelines
indicate that if a diabetic adult chooses to drink alcohol, his/her daily intake should be kept consistently
modest (for women 10-13 g/d, i.e. one drink/day or less, and for men 20-25 g/d, i.e. two drinks/day
or less). To reduce the risk of nocturnal hypoglycemia in patients on insulin or insulin secretagogues,
alcohol should always be ingested with food.
Putative biological mechanisms
In observational studies, alcohol consumption of 10-30 g/day (one to three drinks/day) is associated with
lower fasting insulin concentrations and lower markers of IR, both under fasting and after glucose load.
On the other hand, a negative effect has been found on blood pressure, which increases proportionally
to the amount of alcohol consumed. Most intervention studies suggest that a consumption of
25-40 g ethanol /day (up to 4 drinks/day), improves lipid profile and IS as well as serum adiponectin
in menopausal women, while in men it seems to have no influence on IS and body fat distribution
and it may even promote hepatic steatosis. Of interest, liver histology rather than lipidemic profile is
associated with cardiovascular risk in NAFLD and other cirrhotic and non-cirrhotic liver disease of
varying etiology. These findings are in agreement with recent evidence suggesting that NAFLD is the
precursor rather than a mere ‘manifestation’ of the MetS.
Conclusion
Available data do not enable physicians to suggest that patients with NAFLD and/or T2DM should
be encouraged to drink alcohol to reduce the risk of progression of their disease. Likewise, it remains
uncertain whether patients with NAFLD/T2DM should be discouraged from drinking alcohol in cases
where they consume moderate amounts (namely <20/30 g/daily). Further studies are eagerly awaited to
address these clinically relevant questions.
100 Postgraduate Course Syllabus • Metabolic Liver Disease
between metabolic factors and alcohol in increasing the risk of HCC [5].Another important consideration
is that alcohol consumption may worsen both hypertriglyceridemia and hyperuricemia, which may be
a concern in patients with NAFLD. Comparative analysis of guidelines has led to the conclusion that
heavy alcohol consumption should be discouraged; meanwhile light to moderate alcohol consumption
may have favourable effects on lipid metabolism and, perhaps, on liver outcomes. However, in the
absence of randomized controlled trials, all guidelines advise against prescribing low to moderate alcohol
consumption as a preventative / therapeutic strategy for NAFLD [6].
Alcohol and T2DM
Alcohol consumption has always been considered a risk factor for the development of T2DM. However,
recent findings suggest that moderate alcohol intake might actually be associated with reduced incidence
of T2DM and its vascular complications. A meta-analysis of 15 studies on 369,862 patients, followed
up for an average of 12 years, concluded that subjects who consumed 6-48 g/day of ethanol exhibited
a 30% reduced risk of T2DM as compared with teetotallers or consumers of >48 g/day. This effect is
independent of either sex or BMI, although a lower incidence of T2DM was observed in women with
a moderate alcohol intake compared with abstainers [7]. There is some evidence that moderate alcohol
intake also protects against T2DM development in men [8]. Indeed, consumption of 1-3 alcoholic
drinks/day was inversely related to T2DM risk (HR 0.80, 95%CI 0.67-0.94) among middle-aged
and elderly Chinese men [9]. Several studies suggest that the beneficial effect of alcohol on T2DM
development may be at least in part mediated by body fat distribution in the European population [10].
Current guidelines specific to diabetic patients are rather cautious because of the calories and body-
weight issues, as well as some untoward metabolic and vascular effects of alcohol. In brief, such guidelines
indicate that if a diabetic adult chooses to drink alcohol, his/her daily intake should be kept consistently
modest (for women 10-13 g/d, i.e. one drink/day or less, and for men 20-25 g/d, i.e. two drinks/day
or less). To reduce the risk of nocturnal hypoglycemia in patients on insulin or insulin secretagogues,
alcohol should always be ingested with food.
Putative biological mechanisms
In observational studies, alcohol consumption of 10-30 g/day (one to three drinks/day) is associated with
lower fasting insulin concentrations and lower markers of IR, both under fasting and after glucose load.
On the other hand, a negative effect has been found on blood pressure, which increases proportionally
to the amount of alcohol consumed. Most intervention studies suggest that a consumption of
25-40 g ethanol /day (up to 4 drinks/day), improves lipid profile and IS as well as serum adiponectin
in menopausal women, while in men it seems to have no influence on IS and body fat distribution
and it may even promote hepatic steatosis. Of interest, liver histology rather than lipidemic profile is
associated with cardiovascular risk in NAFLD and other cirrhotic and non-cirrhotic liver disease of
varying etiology. These findings are in agreement with recent evidence suggesting that NAFLD is the
precursor rather than a mere ‘manifestation’ of the MetS.
Conclusion
Available data do not enable physicians to suggest that patients with NAFLD and/or T2DM should
be encouraged to drink alcohol to reduce the risk of progression of their disease. Likewise, it remains
uncertain whether patients with NAFLD/T2DM should be discouraged from drinking alcohol in cases
where they consume moderate amounts (namely <20/30 g/daily). Further studies are eagerly awaited to
address these clinically relevant questions.
100 Postgraduate Course Syllabus • Metabolic Liver Disease
