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NAFLD and T2DM NAFLD is closely associated with features of the metabolic syndrome and is regarded as the hepatic manifestation of the syndrome.The amount of intrahepatic fat closely correlates with serum liver enzyme levels and the number of metabolic syndrome features Patients with T2DM have approximately 80% more intrahepatic fat content than age-, sex-, and body weight-matched nondiabetic Controls, and their serum liver enzymes are less representative of the severity of intrahepatic fat accumulation

NAFLD AND T2DM patients with NAFLD and T2DM are also more likely to develop the more advanced forms of NAFLD, such as NASH, advanced fibrosis, cirrhosis, and in some cases hepatocellular carcinoma

Poor glycemic control Because NAFLD is strongly associated with IR, patients With T2DM and NAFLD often have poor glycemic control compared to their counterparts without NAFLD The presence of NAFLD in people with T2DM often makes 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 complications and mortality among T2DM patients The presence of NAFLD among patients with T2DM appears to be an important risk factor for all-cause mortality. A community-based study of T2DM individuals reported that those with NAFLD had a 2.2-fold increased risk of all-cause mortality compared with those without NAFLD; the most common causes of death were malignancy, CVD, and liver-related complications Evidence is mounting that NAFLD is associated with the presence of vascular disease, ie, the most common cause of death in people with T2DM

Evidence Linking NAFLD With Risk of Developing 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 treatment of NAFLD are those commonly used for the treatment of T2DMand exert a rather indirect effect through improvement in IR and glycemia

Statins statins can be used in dyslipidemic individuals with increased baseline liver enzymes and may even produce Some histological benefit in NASH

Lifestyle modifications gradual weight reduction, achieved either by hypocaloric diet alone or in combination with increased physical exercise, can be effective in decreasing hepatic steatosis and necroinflammation (the reduction of hepatic steatosis and necroinflammation is proportional to the intensity of the lifestyle intervention and generally requires a weight loss between 5 and 10%)

Insulin-sensitizing agents Metformin, the first-line choice in oral therapy for T2DM, has beneficial effects on serum aminotransferases and IR but has no significant effect on liver histology and is 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 with histological endpoints that investigated pioglitazone to specifically t reat patients with NAFLD. A recent metaanalysis reported that pioglitazone improved steatosis and necroinflammation, but not fibrosis

Omega-3 polyunsaturated fatty acid (PUFA) supplementation supplementation High doses of omega-3 PUFAs are effective in treating hypertriglyceridemia that is often a feature of NAFLD and T2DM.

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 E It is known that increased oxidative stress occurs in Both NAFLD and T2DM.Consequently, besides targeting IR or lipid synthesis mechanisms per se, another therapeutic option for NAFLD treatment may be to decrease oxidative stress by administration of an antioxidant such as vitamin E. Vitamin E therapy, as compared with placebo, was associated with significant improvements in liver enzymes and some histological features of NASH such as steatosis and necroinflammation

Vitamin D Preliminary 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 ameliorates NAFLD is uncertain, and randomized clinical trials are needed in man.

Vitamin D