Introduction

Type 1 diabetes (T1D) is a chronic autoimmune condition that targets and destroys β-cells in the pancreas [1]. Under normal circumstances, β-cells produce insulin, an essential hormone for several metabolic processes, with one of the main ones being the regulation of blood glucose levels. Without insulin, the body cannot effectively regulate glucose levels, leading to hyperglycaemia (high blood glucose concentration). As a result, for people living with T1D, every day is a constant challenge to keep blood glucose levels within a target range (typically between 3.9 and 10 mmol/L or 70 and 180 mg/dL). Deviations from this range can lead to serious health consequences.

The challenges associated with T1D are substantial and can negatively impact the quality of life. The necessity for constant monitoring of blood glucose levels, insulin administration, and the fear of potential complications such as vision impairment, nerve damage, kidney failure, and heart attack can significantly strain both physical and mental well-being.

Despite the challenges, there is hope. Advances in medical technology and a deeper understanding of the condition enable many people with T1D to lead fulfilling and healthy lives. In this first chapter, we will delve into the intricacies of blood glucose regulation and explore how T1D disrupts this delicate balance. We will also provide an overview of key concepts in T1D management, including insulin therapy, blood glucose management, and continuous glucose monitoring (CGM). This chapter will serve as the foundation for the rest of the book, where we will focus more heavily on exercise and sport.

 

The Incidence and Global Distribution of T1D

The impact of T1D is enormous [2], imposing a significant financial and emotional strain on affected individuals, families, and healthcare systems worldwide. Until recently, precise data on the global prevalence of T1D was limited. However, thanks to the T1D Index initiative from Breakthrough T1D (formally JDRF) and the International Diabetes Federation (IDF) [3], we now have a better understanding of the extent of the condition.

According to the T1D Index, approximately 8.8 million people are currently living with T1D worldwide3, with an overall lifetime risk of one in 250 individuals. However, it is important to note that the risk varies substantially by country and geographical region [4, 5]. Finland has the highest incidence of T1D in the world, with 32.56 cases per 100,000 people [6], followed by Canada with 31.89 cases per 100,000 [7]. Suggested reasons for the higher incidence in these countries include a variety of genetic and environmental triggers, although this remains uncertain [8]. Other regions with notably high T1D prevalence include Sardinia, Norway, and Sweden. In recent decades, there has been an upward trend in the global incidence of T1D [7, 9], particularly among young children [1, 3, 4, 6, 10-12]. Despite extensive research, the underlying reasons for this increase remain unclear [13, 14].

When we think of T1D, many people associate it with children and young adults. However, despite being commonly referred to as ‘juvenile-onset’ diabetes, T1D can be diagnosed at any age 1. In reality, more than 50% of all T1D diagnoses occur when the individual is above 18 years of age [9, 10, 15-17]. Nevertheless, T1D remains one of the most common chronic diseases in childhood [18], with two distinct peaks in presentation: the first between the ages of 5 and 7 years and the second at or near puberty [1, 9, 18, 19].

Living with T1D has been found to significantly reduce life expectancy, with estimates suggesting a decrease of approximately 12 years for individuals diagnosed at the age of 20 [20]. This can be as high as 17 years, depending on the country and age of the individual at the time of diagnosis, particularly in cases of early disease onset [21]. To address this loss of healthy years, the T1D Index has identified four key areas of focus: a) timely diagnosis, b) access to insulin and blood glucose test strips, c) the use of CGM and insulin pumps, and d) the prevention or discovery of a cure for T1D [3]. By prioritising and addressing these areas, we can strive to reduce all-cause mortality in people with T1D. In some countries, there is evidence for improved life expectancy for people living with T1D, largely due to improvements in care, although the data suggest this still does not match general life expectancy [22].

 

Diagnosis & Symptoms of T1D

In T1D, there is typically a rapid progression of glycaemic disturbances, resulting in hyperglycaemia [1, 23]. Hyperglycaemia-related symptoms are the primary indicators that lead to the diagnosis of T1D. The classic triad of symptoms includes excessive thirst (polydipsia), excessive urination (polyuria), and insatiable hunger (polyphagia), accompanied by pronounced hyperglycaemia on a random blood sample [18, 23]. These symptoms are usually accompanied by significant weight loss over a short period (i.e., only a few weeks), general tiredness, or weakness [23]. The four “Ts” are easy-to-remember key symptoms of T1D: Thirst, Toilet, Tired and Thinner. Approximately 30-50% of children with T1D present with diabetic ketoacidosis (DKA) when they are first diagnosed [24, 25], a potentially life-threatening condition [9, 24-26] that we will discuss in more detail later. Insulin deficiency, resulting in the immediate need for insulin administration, is also a hallmark of T1D [18].

In adults, the onset of T1D can be more varied and less pronounced than in children, without the typical symptoms of excessive thirst, frequent urination, and constant hunger [23, 27]. At the time of diagnosis, no single clinical feature can perfectly distinguish T1D from other types of diabetes. However, elevated autoantibodies targeting specific structures associated with the insulin-producing β-cells in the pancreas and a low C-peptide concentration indicate severe endogenous insulin deficiency and help guide the classification process. Other factors, such as age at diagnosis, time to start insulin treatment, and body mass index (BMI), are also considered [1, 27].

Pancreatic autoantibodies are important biomarkers for autoimmune involvement [23]. Seventy to 90% of diagnosed T1D cases have detectable antibodies against specific β-cell proteins [18, 28]. If necessary, checking for these autoantibodies can confirm a diagnosis.

 

How Does T1D Develop?

For a long time, T1D was thought to be a single autoimmune disorder in which the immune system directly attacks the insulin-producing β-cells in the pancreas [18]. However, over the past few decades, a much more intricate and complex understanding of T1D has emerged. We now know that the development of T1D involves a complicated interplay between environmental factors, the microbiome, genetics, metabolism, and the immune system. This complexity varies from person to person, making T1D a truly multifactorial condition [1, 10, 28].

The first conceptual model of how T1D develops 1, as shown in Figure 1, illustrates a sequence of events related to β-cell mass (y-axis) and time (x-axis). The sequence starts with genetic predisposition, followed by an environmental trigger that initiates islet-specific autoimmunity. Subsequently, partial β-cell loss and blood glucose disturbances occur, resulting in clinical onset of T1D (symptoms) and rapid progression to complete β-cell loss [1].