Circadian Etiology of Type 2 Diabetes Mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is a growing global health issue, strongly associated with the obesity epidemic. People with T2DM face a high risk of both microvascular complications (such as retinopathy, nephropathy, and neuropathy) and macrovascular complications (including cardiovascular diseases), due to high blood sugar levels and various aspects of insulin resistance syndrome. Both environmental factors like obesity, poor diet, and lack of physical activity and genetic factors contribute to the multiple physiological disruptions that lead to impaired glucose regulation in T2DM. The main problems in T2DM are insulin resistance and reduced insulin secretion, but at least six other physiological abnormalities also play a role in glucose metabolism dysfunction. Because of these multiple underlying issues, managing T2DM typically requires a combination of several antidiabetic drugs to maintain normal blood sugar levels. Treatment should be not only effective and safe but also enhance patients’ quality of life. While several new drugs are being developed, the most urgent need is for treatments that improve insulin sensitivity, stop the progressive failure of pancreatic β-cells characteristic of T2DM, and prevent or reverse microvascular complications.