What type 1 diabetes is: beta cells and 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 without which glucose from the blood cannot enter your body's cells to be used for energy [1].

Pancreatic beta cells function as a blood glucose sensor directly coupled to an insulin pump. 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 (in which the doses adjust automatically to blood glucose) — not in hybrid mode (with meals entered manually), though, 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 three in ten children and adolescents with type 1 diabetes are diagnosed during an episode of diabetic ketoacidosis, with wide variation between countries, which underscores the importance of early recognition of these warning symptoms, as the figure below shows [4].

Yes, type 1 diabetes is an autoimmune disease. Your immune system loses its tolerance to the pancreatic beta cells, treats them as something foreign, and begins to destroy them. 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].

Type 1 diabetes has a significant genetic basis, associated particularly with HLA (human leukocyte antigen) genes (the ones that help the immune system tell what belongs to you from what is foreign), 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 autoantibodies specific to type 1 diabetes confers a very high risk of future development of the classic form (with hyperglycemia) [6].

Once autoimmunity has started, beta cell destruction continues over time, even though the pace varies widely from one person to another. 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. A low or undetectable blood level of C-peptide (a marker of the body's own insulin) confirms 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:

• Autoimmune type 1 diabetes (type 1A) — the most common, it represents the majority of cases and occurs following autoimmune destruction of beta cells (confirmed by the presence of autoantibodies);
• Idiopathic type 1 diabetes (type 1B) — 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];
• Latent autoimmune diabetes of adults (LADA) — an autoimmune form with adult onset and slow progression of pancreatic beta cell destruction; LADA is not a separate type of diabetes: under the 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];
• Autoimmune diabetes induced by immune checkpoint inhibitors (in the context of cancer immunotherapy) — fulminant onset and a need for insulin to survive [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. The incidence peaks are in childhood, at 4–6 and 10–14 years of age, but the absolute number of new cases diagnosed in adulthood is greater, because adult life covers many more decades. 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 a normal or low BMI (body mass index) 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].