From the Guidelines
No, Type 2 Diabetes Mellitus (T2DM) is not an autoimmune disease. T2DM is primarily characterized by insulin resistance and relative insulin deficiency, where the body's cells don't respond properly to insulin and the pancreas cannot produce enough insulin to overcome this resistance. Unlike Type 1 Diabetes, which is an autoimmune condition where the immune system attacks and destroys insulin-producing beta cells in the pancreas, T2DM does not involve an autoimmune attack, as stated in the most recent guidelines 1.
The pathophysiology of T2DM involves progressive beta cell dysfunction and insulin resistance in muscle, liver, and fat tissues. Key factors contributing to the development of T2DM include:
- Genetic predisposition
- Lifestyle factors such as obesity, physical inactivity, and poor diet
- Aging
While inflammation plays a role in T2DM development, this inflammation is not driven by autoimmune mechanisms but rather by metabolic stress and other factors, as discussed in 1.
Treatment of T2DM focuses on:
- Lifestyle modifications
- Oral medications that improve insulin sensitivity or increase insulin secretion
- Sometimes insulin therapy when beta cell function significantly declines, as outlined in 1 and 1.
It's essential to note that the risk of developing T2DM increases with age, obesity, and lack of physical activity, and it is often associated with a strong genetic predisposition or family history in first-degree relatives, as mentioned in 1.
Given the most recent and highest quality evidence from 1, the primary approach to managing T2DM should prioritize lifestyle interventions and, when necessary, pharmacological treatments that address insulin resistance and deficiency, without considering it an autoimmune disease.
From the Research
Autoimmune Aspects of Type 2 Diabetes Mellitus
- The presence of circulating autoantibodies against β cells and self-reactive T cells in patients with Type 2 Diabetes Mellitus (T2DM) suggests that autoimmunity may play a role in the pathogenesis of the disease 2.
- A distinct clinical entity termed latent autoimmune diabetes of the adult (LADA) has been identified, which combines features of both Type 1 Diabetes Mellitus (T1DM) and T2DM, and is characterized by the presence of autoantibodies against β cells 2, 3.
- Chronic inflammation is thought to contribute to the autoimmune activation in T2DM, with both innate and adaptive immune system components playing a role in the increased secretion of inflammatory cytokines 2.
Overlap between Type 1 and Type 2 Diabetes Mellitus
- Studies have shown that autoantibodies typical of T1DM can be detected in patients with classical T2DM, and insulin resistance can be present in patients with T1DM, suggesting that the boundary between the two types of diabetes is not clear-cut 3, 4.
- The presence of autoantibodies against β cell antigens has been detected in 10-15% of patients clinically diagnosed with T2DM, and insulin resistance has been diagnosed in 37.03% of patients with T1DM 3, 4.
Pathogenesis of Type 2 Diabetes Mellitus
- T2DM is characterized by a heterogeneous loss of islet β cell insulin secretion, usually occurring after the presence of insulin resistance (IR) and is one component of metabolic syndrome (MS) 5.
- The pathogenesis of T2DM is not fully understood, but is thought to involve a combination of genetic and environmental factors, including inflammation, endoplasmic reticulum stress, oxidative stress, and ectopic lipid deposition 5, 6.
- Beta-cell destruction and dysfunction are key features of T2DM, and are thought to be contributed to by a combination of genetic and environmental factors, including chronic increase of plasma free fatty acid (FFA) levels and disturbances in lipid metabolism 6.