Liver :: Insulin resistance and resolution of diabetes mellitus in non-alcoholic fatty liver disease

Diabetic patients with NAFLD are at risk for progressive liver disease. In this study, researchers examined connections between white adipose tissue (WAT, white fat) in the abdomen and medical disorders including insulin resistance (IR, inadequate response to insulin) and diabetes mellitus (DM, a metabolic disorder characterized by high blood sugar) in patients with obesity and NAFLD to evaluate whether cell signaling pathway profiles within WAT are associated with the presence of IR and whether they can predict the resolution of DM after weight loss.

It is important to note that some obese diabetics can completely resolve DM after weight loss.

This study, conducted by researchers at George Mason University in Fairfax, Va., included 144 patients undergoing bariatric surgery. Prior to surgery, 41 percent of these patients had evidence of IR measured by a blood test. Twenty-five percent of the 144 patients had clinically overt DM prior to surgery. At the time of surgery, WAT was collected for protein profiling. The results were analyzed to determine whether this technique could (a) accurately predict IR in obese individuals and (b) identify which diabetic patients were destined to resolve their DM postoperatively.

Comparing patients with IR to those without IR, the phosphorylation levels of 10 proteins were significantly different between these two groups. When comparing 15 diabetics who resolved their DM after weight loss to 10 who did not, 20 proteins were marked as significantly different between the two groups. Nearly all of these proteins are associated with insulin signaling, which leads to abnormal blood glucose levels and diabetes, leading researchers to the conclusion that “prognostic biomarkers” can be developed that can potentially predict resolution of important complications of obesity such as DM.

“Recognition of specific cell signaling pathways using Reverse Phase Protein Microarrays of WAT appears to help differentiate patients with insulin resistance from those without insulin resistance,” according to Zobair Younossi, M.D., of Inova Health System’s Translational Research Centers in Fairfax, Va., and senior author of the study. “With further confirmatory studies, this type of analysis may be effective at predicting resolution of clinically overt DM after weight-loss surgery.”


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