Comparative Evaluation of Whole Body and Hepatic Insulin Resistance Using Indices from Oral Glucose Tolerance Test in Morbidly Obese Subjects with Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a marker of Insulin Resistance (IR). Euglycemic-hyperinsulinemic clamp is the gold standard for measuring whole body IR (hepatic + peripheral IR). However, it is an invasive and expensive procedure. Homeostasis Model Assessment Index for Insulin Sensitivity (HOMA-IS), Quantitative Insulin Sensitivity Check Index (QUICKI) for hepatic IR and Insulin Sensitivity Index (ISI0,120), and Whole Body Insulin Sensitivity Index (WBISI) for whole body IR are the indices calculated after Oral Glucose Tolerance Test (OGTT). We used these indices as noninvasive methods of IR (inverse of insulin sensitivity) estimation and compared hepatic/peripheral components of whole body IR in NAFLD. Methods. 113 morbidly obese, nondiabetic subjects who underwent gastric bypass surgery and intraoperative liver biopsy were included in the study. OGTT was performed preoperatively and the indices were calculated. Subjects were divided into closely matched groups as normal, fatty liver (FL) and Non-Alcoholic Steatohepatitis (NASH) based on histology. Results. Whole body IR was significantly higher in both FL and NASH groups (NAFLD) as compared to Normal, while hepatic IR was higher only in NASH from Normal. Conclusions. FL is a manifestation of peripheral IR but not hepatic IR.

Peripheral insulin resistance predicts liver damage in nondiabetic subjects with nonalcoholic fatty liver disease

“…Although widely used in epidemiological studies of NAFLD, surrogate indexes of IR have been validated by state‐of‐the‐art techniques in healthy controls and in obese and diabetic subjects but never in an NAFLD population . This is the first study to compare IR/IS in the liver and in the muscle in a group of patients with NAFLD, in the absence of cofactors such as diabetes and overt obesity (BMI >35) that greatly influence IS.…”

Relationship between the indexes of insulin resistance and metabolic status in dairy cows during early lactation

“…Studies on human populations show that fatty liver can develop as a consequence of peripheral insulin resistance. Values of indexes of insulin resistance and lipid profi le are signifi cantly different in comparison to healthy persons [34]. Greater concentration of NEFA blocks insulin signaling in hepatocytes when beta oxidation of fatty acids happens [35].…”

Is the adiponectin-AMPK-mitochondrial axis involved in progression of nonalcoholic fatty liver disease?

“…Despite the focus on the liver, cardiovascular events are the major cause of mortality in NAFLD and there is enormous interest to identify the mechanistic link between NAFLD and cardiovascular events . The initial trigger of excess caloric intake contributes to peripheral insulin resistance in the skeletal muscle and adipose tissue with elevated circulating fatty acids . Increased hepatocyte uptake of fatty acids is followed by cellular partitioning into either β‐oxidation or esterification to triglycerides .…”