📘 What is type 1 diabetes: beta cells, autoimmunity

Beta cells are special cells located in your pancreas. Here, they are grouped in small clusters called islets of Langerhans. Their main role is to produce and release insulin, the hormone that allows glucose from the blood to be better used by your body [1].

Pancreatic beta cells function as a blood glucose sensor directly coupled to an insulin pump. You need to imagine this. The rise in blood glucose after a meal automatically leads to the release of an appropriate amount of insulin. Blood glucose is thus maintained "automatically" between 70 and 140 mg/dl (3.9–7.8 mmol/L). It's as if it were an insulin pump capable of closed-loop operation, not in hybrid mode, but completely [2].

Without enough insulin, muscle, liver, and fat cells cannot efficiently extract glucose from the blood. As a consequence, these cells remain "starved" despite the abundance of glucose in the blood, and blood glucose gradually begins to rise. Your body begins to use fats for its own energy needs, and at some point begins to transform them into acidic substances called ketone bodies. Their accumulation can lead to diabetic ketoacidosis [3].

Symptoms of significant insulin deficiency include excessive thirst, frequent urination, unintentional weight loss, marked fatigue, and blurred vision. Approximately 25–50% of people with type 1 diabetes are diagnosed during an episode of diabetic ketoacidosis, which underscores the importance of early recognition of these warning symptoms [4].

Yes, type 1 diabetes is an autoimmune disease. Your immune system recognizes the pancreatic beta cells as an infection and begins fighting to eliminate it. The markers of this autoimmune attack include autoantibodies against insulin (IA), glutamic acid decarboxylase (GAD), islet antigen 2 (IA-2, tyrosine phosphatase), and zinc transporter 8 (ZnT8) [5].

T1D has a significant genetic basis, associated particularly with HLA genes, but environmental factors are considered to contribute predominantly to triggering the autoimmune process. People with type 1 diabetes have an increased risk of developing other autoimmune diseases, such as Hashimoto's thyroiditis, celiac disease, Addison's disease, vitiligo, or pernicious anemia [5].

Your pancreas no longer produces insulin because the beta cells have been destroyed by the immune system. This autoimmune process begins months or years before blood glucose rises. The presence of two or more T1D-specific autoantibodies confers an almost certain risk of future development of classic T1D (with hyperglycemia) [6].

Once autoimmunity has started, beta cell destruction is progressive and unstoppable. When approximately 80–90% of beta cells have been destroyed (even less in young people), insulin production becomes insufficient, blood glucose rises, and diabetes symptoms begin to appear. Low or undetectable C-peptide levels in the blood confirm severe insufficiency of endogenous insulin production [6].

The name "type 1 diabetes" reflects the modern classification of diabetes, based on the mechanism that produces the disease, not on the age of onset or type of treatment. Type 1 designates a form of diabetes arising through an autoimmune mechanism, associated with absolute insulin deficiency. This classification was standardized to differentiate this disease from other types of diabetes (type 2, gestational, monogenic, etc.) [3].

Previously, type 1 diabetes was also known as "juvenile diabetes" or "insulin-dependent diabetes." These names were abandoned because the disease does not occur exclusively in young people and because the term "insulin-dependent" can create confusion. Some patients with type 2 diabetes may also need insulin in advanced stages of the disease [7].

Yes, type 1 diabetes includes several subtypes. The most common is autoimmune type 1 diabetes (type 1A), which represents the majority of cases and occurs following autoimmune destruction of beta cells (confirmed by the presence of autoantibodies). A second subtype is idiopathic type 1 diabetes (type 1B), in which individuals also present severe insulin secretion deficiency and predisposition to ketoacidosis, but without the presence of autoantibodies. Only a minority of people with type 1 diabetes fall into this category [3].

A particular case is latent autoimmune diabetes of adults (LADA), an autoimmune form with adult onset and slow progression of pancreatic beta cell destruction. According to ADA classification, all forms of diabetes mediated by autoimmune destruction of beta cells, regardless of age of onset, are included in the type 1 diabetes (1A) category [8]. Another particular form is autoimmune diabetes induced by immune checkpoint inhibitors (in the context of cancer immunotherapy), with fulminant onset and insulin requirement for survival [9].

The term "insulin-dependent" refers to the fact that you need insulin administered from outside because your body no longer produces it and without it you cannot survive. Without exogenous insulin, your body cannot efficiently use glucose and it accumulates in the blood [3].

Even though the term "insulin-dependent" correctly describes your situation from a treatment perspective, it is no longer officially used in the disease name. The current classification uses the term "type 1 diabetes," being oriented more towards the mechanism of onset, not the type of treatment or age at diagnosis. Dependence on insulin for survival is a characteristic of type 1 diabetes, unlike type 2 diabetes, where insulin may be needed only for better metabolic control [7].

Yes, type 1 diabetes can occur at any age, from infancy to old age. Although it is diagnosed more frequently in children and adolescents, a significant proportion of cases occur in adults. Adult onset can be more variable than in children, sometimes even without classic symptoms, and may progress more slowly toward the need for insulin treatment [10].

Adults can maintain sufficient pancreatic beta cell secretory function for years to prevent ketoacidosis. Adults have a higher chance compared to children of having a temporary remission period immediately after diagnosis. The old concept that type 1 diabetes occurs only in children and type 2 diabetes in adults is incorrect [11].

Type 1 diabetes occurs as a result of autoimmune destruction of pancreatic beta cells, which leads to absolute insulin deficiency. Type 2 diabetes is characterized by a combination of insulin resistance and insulin secretion deficiency, without an autoimmune component. In type 1 diabetes, you generally need insulin from the time of diagnosis, whereas in type 2 diabetes, initial treatment includes lifestyle changes and oral medications, with insulin sometimes needed in more advanced stages [3].

Type 1 diabetes represents 5–10% of all diabetes cases, occurs more frequently at younger ages, is associated with normal or low BMI and with other autoimmune diseases. Type 2 diabetes represents 90–95% of cases, is associated with overweight/obesity, insulin resistance, sedentary lifestyle, and family history of diabetes. However, classification is not always straightforward. Misdiagnosis can occur in up to 40% of adults with actual type 1 diabetes onset, wrongly recorded as type 2 [12]. Obesity does not exclude a diagnosis of type 1 diabetes [11].