Obesity and Type 2 Diabetes: Adiposopathy as a Triggering Factor and Therapeutic Options

Abstract

Obesity and type 2 diabetes (T2DM) are major public health concerns associated with serious morbidity and increased mortality. Both obesity and T2DM are strongly associated with adiposopathy, a term that describes the pathophysiological changes of the adipose tissue. In this review, we have highlighted adipose tissue dysfunction as a major factor in the etiology of these conditions since it promotes chronic inflammation, dysregulated glucose homeostasis, and impaired adipogenesis, leading to the accumulation of ectopic fat and insulin resistance. This dysfunctional state can be effectively ameliorated by the loss of at least 15% of body weight, that is correlated with better glycemic control, decreased likelihood of cardiometabolic disease, and an improvement in overall quality of life. Weight loss can be achieved through lifestyle modifications (healthy diet, regular physical activity) and pharmacotherapy. In this review, we summarized different effective management strategies to address weight loss, such as bariatric surgery and several classes of drugs, namely metformin, GLP-1 receptor agonists, amylin analogs, and SGLT2 inhibitors. These drugs act by targeting various mechanisms involved in the pathophysiology of obesity and T2DM, and they have been shown to induce significant weight loss and improve glycemic control in obese individuals with T2DM.

Keywords: adiposopathy; diabesity; insulin resistance; obesity; type 2 diabetes mellitus.

Figure 1

Illustration of the wide-ranging effects of adiposopathy.

Figure 2

Illustration of the pathophysiological disease drivers in T2DM.

Figure 3

Metformin structure.

Figure 4

Structures of Liraglutide and Semaglutide.

Figure 5

Structure of Tirzepatide.

Figure 6

Cagrilentide structure.

Figure 7

Structures of different SGLT-2 inhibitors.