Fatty Acid Escape Hypothesis: The Pathway to Type-2 Diabetes
The recent updates from world health organization indicate that the number of patients
with diabetes in the world has quadrupled to an estimated 422 million since the publication
of first report by WHO in 1980.Likewise, obesity has doubled globally during the same time-period with more than 1.9 billion
overweight and over 600 million obese adults worldwide. Given the clinical manifestations,
Type-2 diabetes mellitus has always been considered as glucose-centric pathology, characterized by the legendary Hippocratic three “Ps”, i.e., polyuria, polydipsia and polyphagia.
The underlying cause of T2DM is the loss of glucose homeostasis, a condition which is
also shared by Type1 diabetes mellitus. In terms of metabolic derangement,
T1DM and T2DM are on the opposing ends of the disease spectrum: the former is depicted by hypoinsulinemia whereas the latter is characterized by hyperinsulinemia that emanates from body’s
adaptive response to the tissue insulin resistance.
Experimental animal studies have provided genetic evidence supporting the novel dogma that fatty acid (FA)-induced hyperinsulinemia is a driving factor for diet-induced obesity rather than directly inducing obesity
on its own.
Hyperinsulinemia has also been associated with obesity both in animal models and humans
where excessive insulin is considered as a predictor of obesity. The tetrad of insulinemia, insulin resistance,
hyperglycemia and diabetes are closely related with each other in a way that most T2DM patients
will show all these features.
Diabetes Res Open J. 2019; 5(1): 8-17. doi: 10.17140/DROJ-5-140