📘 Modes of onset in type 1 diabetes

Type 1 diabetes mellitus can begin in several ways, the main modulating factor being how quickly pancreatic beta cell function is lost. The most common forms of onset are: classic onset with typical symptoms (frequent urination, intense thirst, high water intake), onset with diabetic ketoacidosis, silent onset discovered incidentally on routine blood tests, and slow onset observed in some adults [1].

The form of onset depends greatly on age. In children and adolescents, onset is usually rapid and dramatic, compared to adults, in whom symptoms can develop gradually, over the course of months or years. Early recognition of symptoms removes the risk of a severe onset with ketoacidosis [1].

Diabetic ketoacidosis is a serious, life-threatening acute complication. It occurs when insulin deficiency becomes so severe that the body starts to use fats as the main energy source. Ketone bodies start to accumulate in the blood, where they alter the body's acid-base balance, being acidic substances. Ketoacidosis is defined by blood glucose ≥200 mg/dl (≥11.1 mmol/L), elevated ketone bodies (β-hydroxybutyrate ≥3.0 mmol/L) and metabolic acidosis with pH below 7.3 or bicarbonate below 18 mmol/L [2].

Symptoms include nausea, vomiting, abdominal pain, rapid and deep breathing, the smell of acetone in the exhaled breath, marked dehydration and sometimes altered consciousness. Ketoacidosis at onset is a medical emergency and requires immediate hospitalization. Approximately half of children with newly diagnosed T1D present with ketoacidosis, and children with a family history have an even higher risk of severe onset [3].

"Classic" onset refers to the appearance of typical symptoms of unbalanced diabetes. The hyperglycemic triad consists of frequent urination in large amounts (polyuria), intense and persistent thirst (polydipsia) and unintentional weight loss. To these are often added fatigue, blurred vision, the sensation of exaggerated hunger and, in children, the return of bedwetting at night (enuresis). These symptoms appear when blood glucose exceeds the renal threshold, which is 180 mg/dl (10 mmol/L). Above this threshold, glucose in the blood begins to be eliminated through urine, dragging water from the body along with it [4].

Symptoms usually develop over a few weeks, and sometimes even within just a few days. Recognizing them is essential because it allows rapid diagnosis and the initiation of life-saving insulin treatment, before the patient enters ketoacidosis. If you notice this combination of symptoms in yourself or in a family member, it is important to see a doctor as soon as possible for a control blood glucose. A simple finger-prick test can confirm or rule out the suspicion of diabetes [4].

Silent onset means discovering diabetes without dramatic symptoms, through routine blood tests or screening programs. It occurs much more rarely compared to classic onset or onset through ketoacidosis and is observed especially in adults, in first-degree relatives of a person with T1D, or in people who participate in screening studies for pancreatic autoantibodies. In these people, blood glucose may be only mildly elevated, and testing thus discovers the disease at an early stage [5].

Early detection, before the appearance of severe symptoms, allows the initiation of treatment before the patient develops ketoacidosis, provides time for therapeutic education, and protects the pancreatic beta cells that are still functioning. This type of onset highlights the value of periodic testing for close relatives of people with T1D, especially for children and young people with a family history and genetic predisposition (HLA) [6].

Yes, T1D can have two patterns of clinical evolution. Acute onset appears in a few days or weeks and reflects a rapid loss of insulin production. This pattern is characteristic of children and adolescents, in whom symptoms set in suddenly and can quickly lead to ketoacidosis. Slow onset is observed especially in adults and unfolds over the course of several months or even years, with less intense symptoms and a gradual loss of pancreatic beta cell function [1].

The slow form, encountered in adults, is sometimes called latent autoimmune diabetes of adults (LADA). These people may initially appear to have type 2 diabetes mellitus and may temporarily respond to oral medications, but eventually progress to insulin dependence. Correct identification of the type of onset is important because it directly influences the treatment plan and the moment when insulin is initiated [7].

T1D can occur at any age, from the first year of life to advanced periods of old age, but there are two typical incidence peaks in children. The first peak appears between 4 and 6 years, and the second, more pronounced, between 10 and 14 years, during puberty. These stages correspond to hormonal and immunological changes that can accelerate the destruction of pancreatic beta cells [8].

Although it was traditionally considered a disease of childhood, recent data show that the majority of cases are diagnosed in adulthood. In adults, onset can appear at any time and is sometimes misdiagnosed as T2D. Thus, age at diagnosis is no longer a sufficient criterion for establishing the type of diabetes, and evaluation of the clinical picture and possibly additional tests such as pancreatic autoantibodies and C-peptide are necessary [9].

In young children, under 5 years, onset is the most rapid and the most severe. Symptoms set in within a few days, and the risk of ketoacidosis at diagnosis is the highest. Young children cannot clearly express thirst or fatigue, and severe dehydration and vomiting can be confused with gastroenteritis. In adolescents, classic symptoms are easier to recognize but can be masked by the natural changes of puberty or by weight loss attributed to growth [1].

In adults, onset is usually slower, with moderate symptoms, which evolve over weeks or months. Adults can preserve a residual insulin production that temporarily protects them from ketoacidosis. For this reason many adults are misdiagnosed as having T2D. This aspect explains why in adults (especially young ones) it is important that the diagnosis not rely only on age, but also on specific tests that can bring to light the autoimmune nature of the disease [10].

In people who already have pancreatic autoantibodies and a partial loss of β-cell function, certain factors can accelerate the transition to clinically manifest disease. The best-known triggering factors are viral infections, such as enterovirus infections (especially Coxsackie B) and SARS-CoV-2 infection. Intense physical stress, major trauma, surgical interventions and puberty can also hasten onset [11].

Certain medications, such as corticosteroids, can precipitate ketoacidosis in vulnerable people, already on their way toward T1D onset. Intense psychological stress is also considered a possible aggravating factor. It is important to understand that these factors are not the cause of type 1 diabetes, but only accelerate the clinical manifestation of an autoimmune disease already present, which had been silently evolving for months or even years and was going to become clinically manifest anyway, just later [11].

In the presence of vomiting, hospitalization is necessary at the onset of T1D, especially in children and adolescents. Hospitalization allows metabolic stabilization, correction of dehydration and electrolyte imbalances, safe initiation of insulin therapy and therapeutic education for you and your family. In patients who present with ketoacidosis, hospitalization, sometimes even in the intensive care unit, is mandatory [12].

If you only have hyperglycemia, especially in some adults with slow onset, without ketoacidosis, without severe dehydration and with moderate symptoms, treatment can be initiated on an outpatient basis, if there is close supervision and rapid access to specialists. Regardless of where treatment begins, the initial period includes learning insulin administration, recognizing hypoglycemia, blood glucose monitoring and the basic principles of nutrition for T1D. This initial education is the foundation for good long-term control [12].

Insulin therapy should be initiated as quickly as possible after diagnosis, ideally on the same day type 1 diabetes is confirmed. In patients who present with ketoacidosis, insulin is administered intravenously, together with the measures for correction of dehydration and electrolyte imbalances, according to standard protocols. In patients without ketoacidosis, insulin is initiated directly subcutaneously, in doses adjusted to weight and to the value of blood glucose [13].

Early initiation of insulin rapidly removes the acute symptoms, prevents progression to ketoacidosis and helps preserve the function of residual beta cells, which is associated with better long-term glycemic control. In adults with slow onset, delaying the introduction of insulin in the treatment scheme and prolonged use of only oral medications can lead to long-term metabolic deterioration, which is why early identification of T1D in adults is essential for a good prognosis [13].