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Type 1 diabetes (T1D)

An autoimmune disease that destroys the body’s vital insulin-producing cells. Cannot be cured

T1D is an autoimmune disease in which the body’s own immune system mistakenly breaks down its own insulin-producing beta cells in the pancreas. Insulin is the instrument for transporting the vital nutrient glucose into the cells.

The disease, unlike type 2 diabetes, is not lifestyle related, it strikes randomly, often in the young years, and cannot be cured or prevented through healthier lifestyles.

A subtype of T1D is LADA (Latent Autoimmune Diabetes in Adults), also known as type 1½ diabetes. It is a form of autoimmune diabetes that progresses slowly, and most often the symptoms do not appear until the age of 30.

Treatment of T1D consists of many daily measurements of blood sugar, with a blood glucose meter or continuous glucose monitor (CGM), combined with multiple daily insulin injections, with insulin pen or pump, as well as balancing of diet and activity.

Symptoms of T1D

The initial symptoms of T1D may be nonspecific or be confused with symptoms of other diseases, and there is a risk that the disease will be misdiagnosed or overlooked in the beginning. The typical symptoms, which may occur individually, are:

For most people, the onset of type 1 diabetes occurs suddenly, often resulting in a trip to the emergency room to start insulin treatment and to observe for development diabetic ketoacidosis (DKA), due to a long period with high blood sugar.

However, the start of the disease occurs at a much earlier time when the immune system is activated and begins the attack on the beta cells. The cause of the autoimmune reaction is not fully understood, but there are many indications that the combination of genetic predisposition and an environmental trigger, such as a viral infection can initiate the immune activation. Thus, first-degree relatives are 15 times more likely to develop T1D.

Activation of the immune system leads to the development of a single autoantibody, and over time, more can develop. Almost all who develop two or more diabetes related autoantibodies (stages 1 and 2) are diagnosed with T1D at some point (stage 3). The symptoms usually do not appear until stage 3 has been reached [1]

Living With T1D

In T1D, the blood sugar must be measured many times daily, with a blood glucose meter or continuous glucose monior (CGM), multiple daily insulin injections must be taken, with an insulin pen or pump, and diet and activity must be balanced accordingly: If the blood sugar becomes too low, there is a risk of insulin shock and coma, and if it becomes too high, diabetic ketoacidosis (DKA) and a long-term risk of developing debilitating complications.

Balancing all variables is a difficult task and therefore national treatment goals are not reached, resulting in complications and over mortality.

Prevalence and Incidence

Reliable estimates for the number of people with T1D (prevalence) are difficult to find. For this reason, only prevalences for a selected group of countries are shown in the table below. Except for Finland, which has an unexplained high prevalence, the number of people with type 1 diabetes generally is around 500 per 100,000 or 0.5% of the population. Based on this prevalence, the number of people with T1D in EU is 2.2 million and Europe 3.7 million. JDRF estimates the global number of people with type 1 diabetes to be 18.2 million [2].

The number of new cases of T1D (incidence) is increasing worldwide, but there is considerable variation from region to region with some having much higher incidence rates than others. The reasons for this are unclear, but the rapid increase over time makes it impossible to explain by genetic predisposition alone. Other factors must play a role as well, perhaps lifestyle-related changes or the declining incidence of infections in Western countries (the hygiene hypothesis).

Of particular concern is the sharp increase in T1D among children due to an increasingly lower age of the disease start. T1D has developed into one of the most common chronic diseases among children. No explanation has been found for this shift, which seems to be particularly pronounced in the northern countries, see diagram below [3].

Treatment Goals and Outcomes

The most important measure of treatment outcome T1D is the level of glycemic control. Periodic measurement of hemoglobin A1c (HbA1c or in short A1c) in a blood test gives a picture of the blood sugar level in the most recent period (long-term blood sugar). For many years, glycemic control in type 1 diabetes has been primarily assessed with the HbA1c test, and it is still considered the most important metric, although new technology has made other relevant metrics accessible.

The general aim is for HbA1c to be as close to the limit value (48 mmol/mol) for healthy individuals as possible, while avoiding episodes of hypoglycemia (acute low blood sugar). The American Diabetes Association (ADA) recommends a clinical treatment target for HbA1c in type 1 diabetes at ≤53 mmol/mol [4]. Recommendations in many EU countries and the Nordic countries, are at the same level.

The landmark Diabetes Control and Complications Trial (DCCT), together with several follow-up studies, have shown that reaching the 53 mmol/mol target, versus an HbA1c level of 75 mmol/mol, is associated with 50–76% reductions in rates of development and progression of microvascular (retinopathy, neuropathy, and diabetic kidney disease) complications [4].

The diagrams above show HbA1c outcomes by age group as reported in two registers on each side of the Atlantic [5]. Diagram 1 shows the mean HbA1c and diagram 2 the percentage reaching the target of 53 mmol/mol. The data indicate that the teenage period is the most difficult, and that in Europe better results seem to be achieved than in the United States. On both sides of the Atlantic, however, only a minority reach the treatment goal for HbA1c.

Denmark:

The clinical treatment target for HbA1c in Denmark for type 1 diabetes is ≤53 mmol/mol [6]. The table below shows HbA1c outcomes by region [7]. The data demonstrates that fewer than 25% of patients with type 1 diabetes achieve the goals for HbA1c.

HbA1C does not provide a measure of glycemic variability or hypoglycemia. The use of CGM gives patients and caregivers access to metrics such as time in, above, and below range (TIR), mean glucose, and glycemic variability, which are important to assess glycemic control more precisely.

Economic Impact

The cost of T1D is substantial and it is important to include all elements to get the complete picture [2].

Direct medical costs include all costs to the delivery of health care (e.g. drugs, test supplies, costs of ambulatory, inpatient, and nursing care).

Direct non-medical costs include transportation costs to access care, trained caregiver time, and specialized daycare.

Productivity costs (indirect costs resulting from loss of productivity) includes costs related to income loss, absenteeism, presenteeism, disability payments, and life insurance payments for patients and caregivers.

In addition, there are significant indirect costs related to reduced quality of life. However, these have been omitted due to limitations in the economic literature on the disease.

The annual cost per type 1 diabetes patient in USA and Europe is shown in the diagram above. Factoring in the number of pediatric and adult patients, yields a cumulative economic burden for all patients in the US of ~$30B per year. The economic burden for all patients in Europe is at the same level, ~$30B per year. Extrapolating to global regions suggests a worldwide annual type 1 diabetes cost burden of ~$90B [2].

Many studies suggest that the major driver of costs is that of hospital admissions relating to complications, both acute and chronic [8].