Hypoglycaemia, Hyperglycaemia and Diabetic Ketoacidosis: What Are They and Why Do They Happen?

In T1D, metabolic disturbances happen because the body doesn’t produce enough insulin [23]. This lack of insulin can lead to several metabolic issues, such as ketoacidosis. On the other hand, too much insulin (hyperinsulinemia) can cause hypoglycaemia.

 

The Dangerous Situation of Diabetic Ketoacidosis (DKA)

The absence of insulin in T1D poses serious risks [23]. If insulin is not available, for example, due to an insulin pump malfunction or a blocked catheter, glucose can’t be used properly by the body’s tissues, and normal glucose metabolism (glycolysis) can’t take place. This results in insufficient amounts of oxaloacetate, which is needed for the Krebs cycle (a crucial energy-generating process). Without oxaloacetate, acetyl CoA concentrations will increase abnormally, and acetyl CoA will be diverted to an alternative metabolic pathway called ketogenesis, which results in the production of ketone bodies.

Ketone bodies are acidic by-products of fat metabolism, and their accumulation in the blood can lead to DKA. This dangerous condition requires prompt treatment and is characterised by high ketone levels, normally but not necessarily high blood glucose levels, and low blood pH. When treating DKA, the primary goal is to suppress ketone production by administering insulin, which resolves the acidosis. Additional cornerstones of DKA treatment are replacing lost fluids and correcting electrolytes and glucose levels.

 

Hypoglycaemia

Hypoglycaemia mainly occurs in people with T1D due to their insulin therapy. Since they can’t naturally decrease their circulating insulin levels when needed (such as during physical activity), they may experience low blood glucose levels.

Early symptoms of hypoglycaemia include:

●        Dizziness

●        Hunger

●        Blurred vision

●        Difficulty concentrating

●        Irritability

●        Headache

●        Adrenergic symptoms such as tremors, sweating, palpitations, and pale skin (when blood glucose is <65-70 mg/dL or <3.6-3.9 mmol/L).

As blood glucose levels drop further, more severe neuroglycopaenic symptoms (cognitive impairments, behavioural changes, and psychomotor abnormalities) may occur due to the brain’s glucose deprivation (<50-55 mg/dL or <2.8-3.1 mmol/L), potentially leading to seizures and coma at even lower glucose levels [39].

Severe hypoglycaemia is a dangerous side effect of insulin treatment and can be life-threatening [41, 42]. Repeated exposure to hypoglycaemia may have long-term effects, impacting brain function, causing cognitive decline, and increasing the risk of cardiovascular events and mortality [43].

People with T1D must be aware of the symptoms of hypoglycaemia, monitor their blood glucose levels regularly, and have a plan in place to treat hypoglycaemia promptly to avoid severe complications.

 

Therapies and Management Strategies for T1D

Currently, there is no cure for T1D. The management of this condition involves four key components [23].

(1) Insulin Therapy: This is the main pharmacological treatment. If needed, other medications may be used to lower cardiovascular risk, such as blood pressure medications and cholesterol-lowering drugs.

(2) Nutrition: This includes carbohydrate counting, maintaining a healthy and balanced diet with the right mix of macronutrients, and timing of insulin around meals.

(3) Physical Activity and Exercise: This will be discussed thoroughly throughout the rest of this book.

(4) Education: This is crucial for managing the other three components.  In recent years, technology, such as glucose monitoring devices, insulin pumps, smart insulin pens, and automated insulin delivery (AID) systems, have become increasingly available and important for glucose management.

 

Insulin Therapy: The Cornerstone of T1D Management

People with T1D require lifelong insulin replacement therapy to manage their blood glucose levels. With insulin therapy, people with T1D are trying to mimic human physiology, which is extremely challenging to achieve [23, 44]. This regimen of insulin dosing includes:

Insulin is typically administered subcutaneously, either via multiple daily injections (MDI) using insulin pens in a basal-bolus regimen or via continuous subcutaneous insulin infusion (CSII) using an insulin pump that delivers small amounts of fast-acting insulin continuously with additional boluses as needed.

Effective insulin therapy requires education and frequent adjustments based on carbohydrate intake, physical activity, and illness or stress [1, 23, 44]. While regular human insulins are still used, insulin analogues (genetically modified insulins) are becoming more common. These analogues work differently, with varying onset times and durations of action. In recent years, newer insulin analogues have been developed to either further increase the speed of absorption of insulin from the injection site into the bloodstream or prolong insulin action for up to 7 days. These are now available for clinical use [45, 46].

 

Automated Insulin Delivery (AID) Systems

An AID system, also known as an artificial pancreas or closed-loop system [47], is a technology designed to mimic as closely as possible the functions of a healthy pancreas for people with T1D. AID systems are made up of three components: a CGM, an insulin pump, and a smart algorithm that links the two devices, allowing them to communicate with each other (Figure 5). The CGM tracks your glucose levels every few minutes, and the algorithm uses that data to instruct the pump to deliver the right amount of insulin required to maintain a certain pre-determined target glycaemic level. It may even tell the pump to suspend insulin delivery if glucose levels are below a certain threshold. Therefore, the AID system can alleviate the burden of diabetes management and improve time in range (TIR).

There are different types of AID systems: