Introduction 

Diabetes mellitus is a chronic metabolic disorder which is characterised by high blood glucose levels, or hyperglycaemia.¹ It occurs due to problems with insulin, which is a hormone that plays a crucial role in regulating blood sugar. These problems may involve the insufficient production of insulin or resistance to insulin. Diabetes can be categorised into Type 1 and Type 2. Type 1 diabetes occurs when the body’s immune system attacks cells that produce insulin in the pancreas. Type 2 diabetes occurs when the body becomes resistant to insulin or doesn’t produce enough insulin. 

The global rate of diabetes mellitus is continuing to rise, which means that understanding its physiology is becoming increasingly important. The action of insulin is important for glucose metabolism and is also part of a complex hormonal network that maintains energy balance in the body. Disruptions to this system can have widespread effects and affect multiple areas of the body. Moreover, due to rising childhood obesity rates, an increasing number of children and adolescents are being diagnosed with diabetes.⁸ Therefore, early interventions and awareness of hormonal dysregulation are crucial to prevent long-term complications and reduce healthcare burdens.⁹

Normal physiology of insulin and glucose regulation 

In a healthy person, insulin is produced by the beta cells of the pancreas. This usually happens after meals, in response to rising blood glucose levels. Insulin helps the body cells to take in glucose to use for energy and stores excess glucose in the liver as glycogen. It also prevents the liver from releasing too much glucose into the bloodstream. Other hormones, such as glucagon, cortisol, growth hormone and adrenaline, counteract the effects of insulin. This usually occurs at a higher level during fasting or stress to ensure blood sugar levels don’t drop too low. This hormonal balance is essential for maintaining healthy glucose levels.

Pathophysiology of diabetes mellitus

Type 1 diabetes mellitus

Type 1 diabetes is an autoimmune condition where the immune system attacks and destroys the beta cells in the pancreas, leading to insulin deficiency. Without insulin, glucose cannot enter cells and remains in the bloodstream, causing hyperglycaemia. This form of diabetes is often diagnosed in children and young adults and requires insulin therapy.²

Type 2 diabetes mellitus

In Type 2 diabetes, the body becomes resistant to insulin, which means that cells don’t respond to it properly. Over time, the pancreas also produces less insulin. This leads to persistently high blood sugar. Type 2 diabetes is more common in adults and is strongly linked to obesity, lack of physical activity and genetic factors.³

In both types of diabetes, the central problem is the inability to maintain glucose homeostasis due to insulin dysfunction. In Type 1 diabetes, the autoimmune destruction of beta cells occurs gradually, but symptoms can appear suddenly once critical insulin loss occurs. This autoimmune process is thought to be triggered by genetic susceptibility and environmental factors, where immune cells mistakenly target pancreatic tissues.

In Type 2 diabetes, insulin resistance is often first observed in muscle and fat cells, where glucose uptake becomes inefficient. Over time, the liver also becomes insulin resistant, leading to increased hepatic glucose production even when blood sugar levels are already high. The pancreas initially compensates by increasing insulin output, but the chronic demand eventually leads to beta cell dysfunction. This progressive loss of insulin secretion distinguishes advanced Type 2 diabetes from early stages.

Additionally, both forms of diabetes are associated with glucotoxicity and lipotoxicity.¹² Chronically elevated glucose and free fatty acids damage beta cells and impair insulin signalling pathways. Oxidative stress and inflammation further contribute to the metabolic dysfunction, creating a vicious cycle that worsens glycaemic control over time.

Hormonal dysregulation in diabetes 

Type 1 and Type 2 diabetes both involve disrupted insulin function, but the mechanisms differ. In Type 1 diabetes, there is almost a complete lack of insulin due to beta cell destruction. In Type 2 diabetes, insulin is present but not used effectively by the body. Furthermore, people with diabetes often have abnormal levels of other hormones, such as glucagon, which can further raise blood sugar levels.⁴ In Type 2 diabetes, fat tissue also releases inflammatory molecules and hormones (called adipokines) that interfere with insulin function and worsen insulin resistance.⁵

Apart from insulin and glucagon, many other key hormones contribute to the hormone fluctuations observed in diabetes. Amylin, a hormone that goes out with insulin from beta cells, is often low in people with Type 1 diabetes and some with Type 2.¹⁰ Amylin helps keep blood sugar levels steady by slowing down the emptying of your stomach and helping you feel fuller for longer. Its absence can lead to sugar spikes after you eat.

Incretin hormones, such as GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide), are also affected. These hormones are released from the gut in response to food intake and normally enhance insulin secretion. In Type 2 diabetes, the effect of incretin is abolished, reducing the body’s ability to release insulin efficiently after meals.

Cortisol and growth hormone can become dysregulated in diabetes. Elevated cortisol levels, often linked to chronic stress, can increase blood glucose by stimulating gluconeogenesis in the liver. Similarly, excess growth hormone can worsen insulin resistance. The complex interplay between multiple hormones highlights that diabetes is not only a disorder of insulin but a broader hormonal condition. 

Diagnosis and treatment strategies 

Diabetes is diagnosed through blood tests. These include measuring fasting blood glucose, HbA1c (which reflects average blood sugar levels over the past 2–3 months), and oral glucose tolerance tests.⁶ A diagnosis can also be made if someone has typical symptoms and a single random blood sugar reading of 200 mg/dL or higher.⁷ In some cases, further tests, such as autoantibody screening, are used to confirm Type 1 diabetes.

Treatment Strategies

For Type 1 diabetes

People with type 1 diabetes must take insulin injections for life, as their bodies do not produce insulin. These are often given as a combination of long-acting and short-acting insulin. Careful monitoring of blood glucose and attention to diet and exercise are also essential.

For Type 2 diabetes

Treatment usually begins with lifestyle changes, such as healthy eating, regular physical activity, and weight loss. If these are not enough to control blood sugar, medications like metformin are used. Other drugs can be added if needed, and in some cases, people with Type 2 diabetes may also need insulin injections.

Future directions 

Research is ongoing to find better treatments for diabetes mellitus. Some of the advancing areas of research include artificial pancreas systems that automatically adjust insulin delivery, immunotherapies to prevent or delay Type 1 diabetes and stem cell therapy to regenerate cells that produce insulin. Scientists are also exploring more personalised approaches to treating diabetes based on individual differences in genetics, hormone levels and metabolic profiles.

One area gaining significant attention is the development of gene therapy, which involves modifying or correcting the genetic causes of diabetes.¹¹ This area focuses on altering the genes that are involved in diabetes. Another advancing field is the use of smart insulin formulations, which only activate when blood glucose levels are high and remain inactive when glucose levels are normal. This could significantly reduce the risk of hypoglycaemia and improve the quality of life for patients who are insulin-dependent. 

Additionally, digital health tools are transforming diabetes self-management. Continuous glucose monitors (CGMs), insulin pumps and mobile health apps can track glucose levels and insulin use, offering more precise control.

Summary

Diabetes mellitus is a complex hormonal disorder that arises due to problems with insulin, a key hormone responsible for maintaining normal blood glucose levels. This results in disrupted glucose regulation, which can lead to serious long-term health consequences if left unmanaged.

Importantly, Type 1 and Type 2 diabetes have different causes and progression. Type 1 diabetes is an autoimmune condition where the body’s immune system destroys the beta cells in the pancreas, leading to an absence of insulin. It typically develops in childhood or adolescence and always requires lifelong insulin therapy. In contrast, Type 2 diabetes is primarily caused by insulin resistance (where the body's tissues become less responsive to insulin) and is often accompanied by a gradual decline in insulin production. It usually occurs in adulthood and is strongly associated with lifestyle factors such as obesity and physical inactivity.

Understanding these distinctions is critical for accurate diagnosis, effective management and treatment. Ongoing research into both forms of diabetes continues to provide insight into their underlying mechanisms and points toward more personalised, targeted therapeutic approaches in the future.