MASLD/MASH and Insulin Resistance
Type 2 Diabetes
Understanding Type 2 Diabetes: Causes and Consequences
Type 2 Diabetes (T2D) accounts for 90% of all diabetes cases and is clinically defined by a fasting blood glucose level above 1.26 g/L. T2D is caused by a complex combination of environmental factors—such as diet, sedentary lifestyle, and exposure to endocrine disruptors—and genetic predisposition, which increases an individual's sensitivity to these environmental influences.
In the stereotypical view of T2D, overweight and obesity contribute to insulin resistance in the liver, skeletal muscles, and adipose tissue. In response, insulin-producing cells (β-cells in the pancreas) compensate by increasing both their function and number in an attempt to maintain normal blood glucose levels (normoglycemia). Over time, β-cells become exhausted, can no longer produce sufficient insulin, and begin to die. This critical event leads to the onset of T2D.
The severity of T2D arises from the many comorbidities resulting from chronic hyperglycemia, primarily due to micro- and macrovascular complications. These vascular lesions can lead to cardiovascular diseases, strokes, kidney disorders (nephropathies), and neurological impairments, among others. Therefore, maintaining patients within a tight glycemic range is crucial.
The Global Burden of Type 2 Diabetes
By 2025, the International Diabetes Federation estimates that 11.1% of the global population will be affected by diabetes, while the World Health Organisation reported a prevalence of 8.5% in 2014. This corresponds to over 500 million people living with T2D worldwide and reflects the dramatic rise in incidence over recent decades. As of 2025, T2D remains incurable and requires lifelong medication from the time of diagnosis. Consequently, T2D represents not only a major public health issue but also a significant economic burden on society.
Current Treatments and Future Directions
Dietary and lifestyle changes are the first line of intervention. If these measures fail to normalise blood glucose levels, clinical management requires anti-diabetic medications. These treatments can improve insulin sensitivity, enhance insulin secretion, reduce endogenous glucose production, increase glucose elimination via urine, or modulate appetite regulation, leading to weight loss. However, none of the current treatments are curative and may eventually result in poor glycemic control. At that point, exogenous insulin administration becomes necessary, which can significantly affect the patient’s quality of life. This highlights the urgent need for further research to better understand T2D and to develop new therapeutic strategies.
