Nonalcoholic Fatty Liver Disease

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A NovelCardiometabolic Risk Factor for Type 2 Diabetes

NAFLD and T2DMNAFLD is closely associated with features of the metabolic

syndrome and is regarded as the hepatic manifestationof the syndrome .The amount of intrahepatic

fat closely correlates with serum liver enzyme levels andthe number of metabolic syndrome features Patients

with T2DM have approximately 80% more intrahepaticfat content than age-, sex-, and body weight-matched

nondiabetic

Controls, and their serum liver enzymes are lessrepresentative of the severity of intrahepatic fat

accumulation

NAFLD AND T2DM

patients with NAFLD and T2DM arealso more likely to develop the more

advanced forms ofNAFLD, such as NASH, advanced fibrosis,

cirrhosis, andin some cases hepatocellular carcinoma

Poor glycemic controlBecause NAFLD is strongly associated

with IR, patients With T2DM and NAFLD often have poor

glycemic controlcompared to their counterparts without

NAFLD The presence of NAFLD in people with

T2DM oftenmakes it difficult to obtain good glycemic

control

stable glycemic control with in insulin treated T2DM patient it has

been demonstrated that the intrahepatic triglyceride content

was more closely correlated with the daily insulin dose

and the ability of insulin to suppress hepatic glucose production

and better explained the interindividual variation

in insulin requirements

In addition, when the relationship between NAFLD

and peripheral glucose metabolism was explored in

healthy individuals, the association between the intrahepatic

triglyceride content and systemic IR was stronger

than the association with intramyocellular lipid content,

visceral fat content, or sc fat content

NAFLD and risk of chronic diabetic complicationsand mortality among T2DM patients

The presence of NAFLD among patients with T2DMappears to be an important risk factor for all-cause mortality.

A community-based study of T2DM individualsreported that those with NAFLD had a 2.2-fold increased

risk of all-cause mortality compared with thosewithout NAFLD; the most common causes of death

were malignancy, CVD, and liver-related complicationsEvidence is mounting that NAFLD is associated

with the presence of vascular disease, ie, the most commoncause of death in people with T2DM

Evidence Linking NAFLD With Risk ofDeveloping T2DM

modestly increased serum GGT and ALT levels were independent,

long-term predictors of incident T2DM in

both sexes

Treatment Options for NAFLD

Presently, there is no licensed treatment for human NAFLD

Most interventions evaluated for the treatmentof NAFLD are those commonly used for the

treatment ofT2DMand exert a rather indirect effect through

improvementin IR and glycemia

Statinsstatins can be used in dyslipidemic

individuals with increasedbaseline liver enzymes and may even

produceSome histological benefit in NASH

Lifestyle modificationsgradual weight reduction,

achieved either by hypocaloric diet alone or in combination

with increased physical exercise, can be effective indecreasing hepatic steatosis and

necroinflammation (thereduction of hepatic steatosis and necroinflammation

isproportional to the intensity of the lifestyle

interventionand generally requires a weight loss between 5 and

10%)

Insulin-sensitizing agentsMetformin, the first-line choice in oral

therapy forT2DM, has beneficial effects on serum

aminotransferasesand IR but has no significant effect on

liver histology andis not recommended as a specific

treatment for liver disease in patients with NAFLD/NASH

Insulin-sensitizing agents Pioglitazone can

be used to treat steatohepatitis in patients with biopsyproven NASH;

there are no randomized clinical trials withhistological endpoints that investigated

pioglitazone tospecifically t reat patients with NAFLD. A recent

metaanalysisreported that pioglitazone improved steatosis

andnecroinflammation, but not fibrosis

Omega-3 polyunsaturated fatty acid (PUFA)supplementation

supplementationHigh doses of omega-3 PUFAs are effective

in treatinghypertriglyceridemia that is often a feature

of NAFLD andT2DM.

Glucagon-like peptide agonist (GLP-1 analog)

GLP-1 agonists have proved to be effective therapies to

improve glycemic control in people with T2DM; and interesting

additional effects of treatment are weight loss,

decreased appetite, and improved IR, which can prove

helpful in people with NAFLD

Vitamin EIt is known that increased oxidative stress occurs in

Both NAFLD and T2DM .Consequently, besides targetingIR or lipid synthesis mechanisms per se, another

therapeuticoption for NAFLD treatment may be to decrease

oxidative stress by administration of an antioxidant suchas vitamin E. Vitamin E therapy, as compared with placebo,

was associated with significant improvements in liver enzymes

and some histological features of NASH such assteatosis and necroinflammation

Vitamin DPreliminary experimental evidence

suggests that via effects in both adipose tissue and liver,

low serum vitaminD levels may predispose to intrahepatic

lipid accumulation and hepatic inflammation, contributing

to the development and progression of NAFLD .However, whether vitamin D supplementation

amelioratesNAFLD is uncertain, and randomized clinical

trials are needed in man.

Vitamin D