Here is a blurb that I found very interesting from “The Journal of Clinical Investigation”.
Obesity is a well-described epidemic in Westernized cultures. In the United States alone, it is estimated that approximately 66% of all adults are overweight and approximately 32% are obese ( 1 ). With obesity comes a variety of adverse health outcomes, such as high blood pressure, insulin resistance, and type 2 diabetes ( 2 , 3 ). Insulin resistance is defined as an inadequate response by insulin target tissues, such as skeletal muscle, liver, and adipose tissue, to the physiologic effects of circulating insulin. The hallmarks of impaired insulin sensitivity in these three tissues are decreased insulin-stimulated glucose uptake into skeletal muscle, impaired insulin-mediated inhibition of hepatic glucose production in liver, and a reduced ability of insulin to inhibit lipolysis in adipose tissue. In fact, insulin resistance is a major predictor for the development of various metabolic sequelae, including type 2 diabetes ( 4 ), and is a defining feature of syndrome X, which is also known as the metabolic syndrome ( 3 ). This syndrome encompasses a constellation of conditions, including insulin resistance, dyslipidemia, hypertension, and obesity, and is often accompanied by hyperinsulinemia, sleep apnea, and other disorders ( 3 ).
In type 2 diabetes, it has been widely established that insulin resistance precedes the development of overt hyperglycemia ( 5 ). The causes of insulin resistance can be genetic and/or acquired. Genetic causes or predispositions toward insulin resistance in prediabetic populations are poorly understood from a mechanistic point of view, although lean, insulin-resistant, prediabetic individuals (e.g., nondiabetic offspring of 2 diabetic parents) can display defects in oxidative metabolism ( 6 ). In addition, inherited defects in the basic insulin signaling cascade have been proposed ( 7 ). Nonetheless, it is likely that any genetic component must interact with environmental factors in order for insulin resistance to develop into a pathophysiologically meaningful abnormality. In Western cultures, the most common acquired factors causing insulin resistance are obesity, sedentary lifestyle, and aging, all of which are interrelated ( 2 , 3 , 8 ). In the presence of a robust compensatory insulin secretory response to insulin resistance, glucose levels can remain relatively normal. However, when insulin-producing pancreatic β cells can no longer compensate for the decreased tissue insulin sensitivity, glucose homeostasis deteriorates and impaired glucose tolerance and eventually frank type 2 diabetes develop ( 5 ).