How type 1 diabetes starts: signs and forms

Type 1 diabetes can begin in several ways, the main difference 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, weight loss), 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 with adults, in whom symptoms can develop gradually, over the course of months or years. Early recognition of the symptoms greatly reduces the risk of a severe onset with ketoacidosis, as the figure below shows [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 its main energy source. Ketone bodies start to accumulate in the blood, where, being acidic, they alter the body's acid-base balance. Ketoacidosis is defined by three criteria occurring together:

• blood glucose ≥200 mg/dL (≥11.1 mmol/L);
• elevated ketone bodies (beta-hydroxybutyrate ≥3.0 mmol/L);
• metabolic acidosis — 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 on the breath, marked dehydration and sometimes altered consciousness. Ketoacidosis at onset is a medical emergency and requires immediate hospitalization. If you suspect ketoacidosis — intense thirst, labored breathing, nausea or vomiting, drowsiness — go to the emergency room straight away, do not wait for an appointment. Approximately three in ten children and adolescents with newly diagnosed type 1 diabetes present with ketoacidosis, with wide variation between countries, and children with a family history have an even higher risk of severe onset [3].

"Classic" onset refers to the appearance of the typical symptoms of uncontrolled 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, excessive hunger and, in children, a return of bedwetting at night (enuresis). These symptoms appear when blood glucose exceeds the renal threshold, usually around 180 mg/dL (10 mmol/L), though it differs from one person to another. Above this threshold, glucose in the blood begins to be eliminated through the 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 blood glucose check. A simple finger-prick test can raise the suspicion of diabetes, but the diagnosis is confirmed by laboratory testing, according to the diagnostic criteria [4].

Silent onset means discovering diabetes without dramatic symptoms, through routine blood tests or screening programs. It occurs much more rarely than classic onset or onset with ketoacidosis. It is seen especially in adults and in first-degree relatives of a person with type 1 diabetes. It is also found in people who take part 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 severe symptoms appear, allows treatment to be started before the patient develops ketoacidosis. It also provides time for therapeutic education and protects the pancreatic beta cells that are still working. This type of onset highlights the value of periodic testing for close relatives of people with type 1 diabetes. Testing matters most for children and young people with a family history and genetic predisposition (HLA, human leukocyte antigen) [6].

Yes, type 1 diabetes can follow two patterns of clinical evolution. Acute onset appears within 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. Symptoms are less intense and the loss of pancreatic beta cell function is gradual [1].

The slow form, seen in adults, is sometimes called latent autoimmune diabetes in adults (LADA). These people may initially appear to have type 2 diabetes and may respond temporarily 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 started [7].

Type 1 diabetes can occur at any age, from the first year of life to advanced 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, 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. In adults, onset can appear at any time and is sometimes misdiagnosed as type 2 diabetes. Thus, age at diagnosis is no longer a sufficient criterion for establishing the type of diabetes. Assessment of the clinical picture is also needed, where appropriate together with additional tests such as pancreatic autoantibodies and C-peptide [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, the 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 that 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 type 2 diabetes. This explains why in adults (especially younger ones) the diagnosis should not rely on age alone. Specific tests are also needed, which can bring to light the autoimmune nature of the disease [10].

In people who already have pancreatic autoantibodies and a partial loss of beta 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 who are already on their way towards type 1 diabetes 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. They only accelerate the clinical manifestation of an autoimmune disease that is already present, which had been evolving silently for months or even years. Most likely, the disease would have become clinically manifest even without these factors, only later [11].

Usually yes, especially in children. At the onset of type 1 diabetes, hospitalization is usually necessary, especially in children and adolescents, and it becomes all the more important if vomiting develops. Hospitalization allows metabolic stabilization, correction of dehydration and electrolyte imbalances, the 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, without ketoacidosis, without severe dehydration and with moderate symptoms, treatment can be started on an outpatient basis. This is the case in some adults with slow onset, provided there is close supervision and rapid access to specialists. Wherever treatment begins, the initial period includes learning how to administer insulin, recognizing hypoglycemia, monitoring blood glucose and the basic principles of nutrition for type 1 diabetes. This initial education is the foundation for good long-term control [12].

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

Early initiation of insulin rapidly removes the acute symptoms, prevents progression to ketoacidosis and helps preserve the function of residual beta cells. Preserved residual beta cell function is associated with better long-term glycemic control. In adults with slow onset, insulin is sometimes introduced too late into the treatment plan. Prolonged use of oral medications alone can then lead to metabolic deterioration, including in the long term. That is why early identification of type 1 diabetes in adults is essential for a good prognosis [13].