A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

Abstract

Type 2 diabetes (T2D), which has currently become a global pandemic, is a metabolic disease largely characterised by impaired insulin secretion and action. Significant progress has been made in understanding T2D aetiology and pathogenesis, which is discussed in this review. Extrapancreatic pathology is also summarised, which demonstrates the highly multifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsible for augmenting insulin secretion from pancreatic beta-cells during the postprandial period. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a much longer half-life have been developed, which are currently an effective treatment option for T2D by enhancing insulin secretion in patients. Interestingly, there is continual emerging evidence that these therapies alleviate some of the post-diagnosis complications of T2D. Additionally, these therapies have been shown to induce weight loss in patients, suggesting they could be an alternative to bariatric surgery, a procedure associated with numerous complications. Current GLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R). Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists have been developed for these sites to test their therapeutic potential. Recent studies have also demonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptors including GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1R mechanisms of activation via different agonists, will likely provide better insight into the therapeutic potential of GLP-1-based therapies to treat T2D.

Associations Between the Metabolic Score for Insulin Resistance Index and the Risk of Type 2 Diabetes Mellitus Among Non-Obese Adults: Insights from a Population-Based Cohort Study

“…It is predicted to increase to 7079 per 100,000 people by 2030, reflecting a continued rising and showing no signs of stabilization worldwide. 3,4 To make matters worse, T2DM can affect an individual's functional capacity and quality of life, leading to significant morbidity and even premature death. 5,6 However, the development of T2DM and related outcomes can be prevented or delayed by timely lifestyle modifications and appropriate pharmacological interventions, which require effective screening strategies and early detection of individuals at high risk for T2DM.…”

D-Pinitol—Active Natural Product from Carob with Notable Insulin Regulation

“…Type 2 diabetes (T2D) is defined by the World Health Organization (WHO) as a “metabolic disorder of multiple etiology characterized by chronic hyperglycemia with disturbance of carbohydrate, fat, and protein metabolism resulting from defects in insulin secretion, insulin action, or both” [ 17 ]. The International Diabetes Federation reported that in 2018, there were 463 million people around the world affected by this disease, and the organization estimates that by 2045, there will be 700 million people affected by it [ 18 ].…”

“…Therefore, in the abovementioned definition of T2D, insulin plays a critical role, and “insulin resistance” is the major cause of this disease. This health disorder is defined as: “a defect in insulin-mediated control of glucose metabolism in tissues—prominently in muscle, fat and liver” [ 17 ], but insulin has various functions in the human body, and they are presented in Table 2 [ 21 ].…”

Epigenetics and Beyond: Targeting Histone Methylation to Treat Type 2 Diabetes Mellitus

“…Diabetes mellitus, a global public health challenge with rapidly increasing morbidity rate, causes a high epidemiological and economic burden on health systems worldwide ( Zimmet et al, 2016 ). This disease serves as a high-prevalence epidemic that currently affects approximately 316 million people, which is estimated to reach 470 million by the year 2035 ( Reed et al, 2021 ). Among the types of diabetes, type 2 diabetes mellitus (T2DM) is a common form, which accounts for nearly 90% of the global prevalence of diabetes ( Dendup et al, 2018 ).…”