Type 2 Diabetes

Type 2 diabetes mellitus is a chronic, progressive disease driven by a complex interplay of genetic, biological, behavioural, and social factors, whose epidemiology has shifted considerably, largely attributable to increasing obesity rates. ^[1] It is clinically diagnosed with the cardinal sign of chronic hyperglycaemia, coupled with dysfunction of pancreatic beta-cells, insulin resistance, and immune inflammation that further exacerbate its pathology. ^[2] The most frequently measured parameters for detecting the disease and its prediabetic precursor are fasting plasma glucose, glycated haemoglobin (HbA1c), and the oral glucose tolerance test. ^[3]

The pathogenesis involves insulin resistance and beta-cell dysfunction, mediated by mechanisms such as beta-cell dedifferentiation, mitochondrial dysfunction, and oxidative stress. ^[4] An unhealthy diet and a sedentary lifestyle are important drivers of the current global epidemic, and early developmental factors such as intrauterine exposures also have a role in later susceptibility to the disease. ^[5] Prediabetes, or intermediate hyperglycaemia, is a preliminary stage in the development of type 2 diabetes, and its two major phenotypes, impaired fasting glucose and impaired glucose tolerance, may represent different pathophysiologies. ^[3]

According to World Health Organization statistics, more than 422 million adults globally were living with diabetes in 2014, with a continuous rise in prevalence expected. ^[6] The number of people with diabetes has quadrupled in the past three decades; about 1 in 11 adults worldwide have diabetes, 90% of whom have type 2 diabetes, and diabetes is the ninth major cause of death. ^[5] Prevalence is increasing in younger people, with early-onset type 2 diabetes diagnosed before 40 years of age associated with more aggressive disease progression and earlier, more severe complications. ^{[1] [7]} Nearly half of all individuals with diabetes are now older adults aged 65 years or over, a group in which comorbidities, susceptibility to hypoglycaemia, and frailty complicate management. ^[8]

Cardiovascular disease is the leading cause of mortality in people with type 2 diabetes, and a significant proportion of that burden cannot be accounted for by conventional cardiovascular risk factors. ^[9] Uncontrolled type 2 diabetes contributes to the onset and progression of micro- and macrovascular diseases including diabetic retinopathy, nephropathy, neuropathy, and atherosclerosis. ^[2] Many cases could be prevented with lifestyle changes such as maintaining a healthy body weight, a healthy diet, physical activity, not smoking, and moderating alcohol, and advanced therapies including SGLT2 inhibitors and GLP-1 receptor agonists offer glycaemic control, weight control, and reduced cardiovascular risk. ^{[5] [4]} Metformin is the first-line pharmacological therapy for type 2 diabetes, lowering glucose chiefly by inhibiting hepatic gluconeogenesis while offering a well-established safety profile and low cost