The Pathophysiology of Type 2 Diabetes Mellitus in Non-obese Individuals: An Overview of the Current Understanding

Abstract

The pandemic of type 2 diabetes mellitus (T2DM) has been largely attributed to the increasing prevalence of worldwide obesity at a geometric rate. However, the number of non-obese patients with T2DM is also on the rise, and it is as high as 60-80% in some Asian countries. These non-obese individuals have certain peculiarities and have a higher mortality rate compared with obese individuals. The pathophysiology of T2DM in non-obese individuals remains poorly understood, and this has an impact on defining its management. This review discusses the current understanding of the pathophysiology of T2DM in non-obese individuals. The definition of T2DM in non-obese individuals remains controversial because of the limited clinical measurements, and the current definition of obesity using body mass index (BMI) is not very helpful as these individuals have BMIs of <25K g/m3, which is considered normal. Many authors have argued that the so-called non-obese people are actually metabolically obese; however, in terms of the measurements clinically available, they are non-obese. The simplistic understanding of the mechanism of the pathophysiology sees it in terms of the balance between insulin secretion and insulin resistance. The pathogenesis of insulin resistance in a lean patient has been proven to be the same as what is seen in an obese individual, but most studies confirm more severe functional insulin secretory defects in lean individuals compared to the obese phenotype. The mechanism underlying this form of T2DM is still poorly defined, and more research is required to understand the mechanism of sarcopenic obesity, which some studies have revealed.

Keywords: non-obese; pathophysiology; type2 diabetes mellitus.