Introduction

Exercise is arguably one of the most challenging aspects of managing type 1 diabetes (T1D). Depending on various factors, it can substantially increase the risk of both hyper- and hypoglycaemia, which can be discouraging, to say the least. Understanding the body’s hormonal responses to different forms of exercise is essential for people living with T1D as it enables the individual to better understand why glucose responds as it does. This chapter aims to explain how exercise-related metabolism changes in people living with T1D and how blood glucose tends to respond depending on the type and intensity of the exercise. The Hormonal Response to Exercise in People without T1D Before we dive into what happens in people with T1D, it’s helpful to understand how the body typically responds to exercise in people without diabetes. As discussed in Chapter 1, people without diabetes have robust mechanisms to stabilise blood glucose within the normal range throughout the day. During exercise, the body employs intricate hormonal mechanisms to maintain glucose homeostasis [1-3]. The intensity and duration of exercise determine how the body’s hormones and nervous system respond, ultimately affecting blood glucose levels [4]. Unfortunately, many of these mechanisms are impaired in people with T1D, which has important implications during and after exercise. Depending on the primary energy systems used, exercise can be broadly categorised as ‘aerobic’ or ‘anaerobic’. Many forms of exercise combine both (mixed), or exercise may be undertaken in an interval style.

How the Body Responds to Aerobic Exercise in People without T1D

During exercise, your muscles need to use glucose at a rate that matches the glucose supplied by the liver and/or gut to prevent hypoglycaemia. As your muscles use more glucose, the liver pumps out more to keep up. To achieve this, in people without diabetes who are doing moderate-intensity exercise, several hormonal mechanisms activate one after the other. These mechanisms make sure that glucose uptake and production are balanced. This keeps blood glucose levels within a narrow range of around 72-106 mg/dL or 4-6 mmol/L [5]. However, some more recent evidence (from CGM data) suggests that glucose may also trend higher than this during high-intensity aerobic exercise [6]. Here’s what happens in someone without diabetes during aerobic exercise:

  1. Insulin Levels Drop: When someone without T1D begins aerobic exercise, the body quickly inhibits insulin secretion, dropping insulin levels to below fasting levels [7]. Since endogenous insulin has a relatively short half-life (around 4-6 minutes), circulating insulin decreases rapidly.

  2. Glucagon Increases: The drop in insulin allows the pancreas to increase glucagon secretion into the portal vein, which stimulates the liver to release glucose [8-10]. The decrease in insulin also makes the liver more sensitive to glucagon, triggering the breakdown of glycogen (a process called glycogenolysis) and the creation of new glucose (gluconeogenesis) [1-3]. As blood glucose levels continue to fall, the body releases other hormones, such as epinephrine, growth hormone, cortisol, norepinephrine, and aldosterone [11, 12]. These hormones increase glucose production from the liver and the breakdown of fats. They also inhibit skeletal muscle glucose uptake, increasing circulating glucose and preventing hypoglycaemia. As exercise intensity increases above 50-60% V ̇O2max, fat oxidation decreases, especially in untrained individuals, and carbohydrates become the predominant fuel [13].

How the Body Responds to High-Intensity or Anaerobic Exercise in People without T1D

High-intensity exercise, where you’re working at over 80% of your maximum aerobic capacity (V ̇O2max), mainly uses muscle glycogen for fuel, with minimal contribution from fat and protein [14, 15]. Even in people without T1D, high-intensity exercise can cause blood glucose levels to rise substantially (up to 144-180 mg/dL or 8-10 mmol/L). Activities such as a 30-second bike sprint [16] or an intense ride to exhaustion lasting up to 10-15 minutes can trigger this response [17-20], which appears to be more pronounced in highly trained individuals [21]. This rise in blood glucose is mainly due to a reported 14-18-fold increase in catecholamines (hormones like adrenaline and noradrenaline), compared to the 2-4-fold increase during low- or moderate-intensity exercise [22]. These increased catecholamines stimulate the liver to increase the breakdown of glycogen into glucose [23], resulting in a temporary rise in blood glucose levels. In response to the rise in blood glucose, the pancreas releases a small amount of insulin. However, the stress hormones released during exercise signal the pancreas to decrease insulin secretion. Additionally, blood lactate concentrations increase 10-20-fold to over 10 mmol/L, as the muscles cannot process all the pyruvate generated by glycolysis. The catecholamines released during high-intensity exercise not only stimulate glucose production by the liver but also limit the amount of glucose the muscles can take up [15]. After a high-intensity workout in people without diabetes, blood glucose levels generally rise slightly compared to baseline (0.5-1.0 mmol/L) [20, 23, 24]. Continuous glucose monitoring (CGM) data from athletes without diabetes have suggested that highly trained athletes may experience even more significant increases in glucose post-exercise, up to around 8-10 mmol/L [20]. However, this increase in glucose in athletes without diabetes appears to be a very transient phenomenon. Insulin secretion increases again after the activity to bring blood glucose levels back to normal and help replenish muscle glycogen stores [15, 24].

Hormonal Responses During Exercise in People with T1D and the Impact on Blood Glucose Levels

Underlying (Patho-)Physiology of Exercise Metabolism in People with T1D

For people with T1D, the hormonal and metabolic responses to exercise are different from those seen in people without T1D, leading to impaired glucose regulation during workouts. Here, we outline the complex interactions between (1) exogenous insulin therapy, (2) defective counterregulatory hormonal responses, and (3) exercise-induced effects on glucose uptake and metabolism [4, 25].

1. Exogenous Insulin Therapy and Insulin Dynamics During Exercise:

Because people with T1D need to administer insulin, they lack the natural decrease in endogenous insulin secretion that usually occurs during exercise [26]. This means they cannot rapidly or adequately lower their circulating insulin levels because the insulin they have already taken continues to be released from under the skin where it was administered, leading to higher-than-normal (supra-physiological) insulin levels. Even the fastest-acting synthetic insulin analogues have half-lives lasting hours rather than minutes, so they cannot mimic the dynamics of a healthy pancreas [27]. The longer half-life of exogenous insulin, along with its entry into the bloodstream from under the skin (as opposed to the portal circulation in people without T1D), results in higher insulin levels at the start of exercise in individuals with T1D [28]. This means circulating insulin concentrations may not decrease as needed [29, 30]. The effects of this relative hyperinsulinaemia (i.e., elevated circulating insulin concentrations in the blood or the failure of insulin levels to drop) during exercise are threefold:

2. Blunted Counter-Regulatory Hormone Response:

In people with T1D, the hormonal relationship between the pancreatic α- and β-cells is disrupted, leading to an impaired counterregulatory response to decreasing plasma glucose concentrations during exercise [31]. This impairment means a blunted release of glucagon and catecholamines in response to impending hypoglycaemia, which diminishes glucose production from the liver [4, 32, 35]. In other words, the protective mechanisms against hypoglycaemia are compromised in people with T1D.

3. Muscle Contractions Stimulate Glucose Uptake: The Exercise-Induced Effects on Glucose Levels

During exercise, muscle contractions stimulate glucose uptake through a mechanism that is independent of insulin. This process involves the movement of glucose transporter proteins (in this case, GLUT4) to the muscle cell surface, facilitating the entry of glucose into the cells [10, 25, 36-41], as shown in Figure 1. This contraction-stimulated (i.e., non-insulin-mediated) glucose uptake remains intact in people with T1D. This is important to note because it explains why exercise can cause glucose levels to drop without insulin. It also means that people with T1D can benefit from enhanced glucose disposal in the muscles during exercise, which can help manage glucose levels and improve overall health.

Another important factor is the rapid exercise-induced increase in insulin sensitivity and the synergistic action between insulin and exercise for glucose disposal in skeletal muscle [38]. In practical terms, glucose levels can fall rapidly during exercise if insulin levels are high. Additionally, blood flow to skeletal muscles significantly increases with exercise [42], potentially further increasing insulin action and insulin-mediated glucose disposal and, thus, the risk of hypoglycaemia.