According to the World Health Organization, 8.5% of the worldwide adult population had diabetes in 2014. In 2016, 4.5 million people in the United Kingdom were living with diabetes, of which 1 million were undiagnosed. What causes diabetes and what does it mean to have diabetes?

Diabetes is a complex and chronic disease that is characterised by elevated, uncontrolled levels of sugar, in the form of glucose, in the blood (hyperglycaemia). Depending on the type of diabetes, progression of the disease may take years before causing specific symptoms. High blood glucose levels may cause damage to blood vessels, the heart, kidneys and eyes, and diabetes may also increase the risk of leg amputations due to infected, non-healing foot ulcers. Among deaths related to high blood glucose levels, 43% occur in people younger than 70 years of age.

How the body regulates blood glucose

Every cell in the body requires glucose, to have the energy to perform its tasks. After a meal, any starches and most other carbohydrates get broken down into glucose by enzymes in the gut, and absorbed glucose raises the blood glucose levels. The body is able to maintain a fairly constant blood glucose level with two key hormones that are produced in the pancreas: insulin and glucagon.

• Insulin is produced by β-cells in the pancreas in response to raised blood glucose levels. It instructs cells to take in glucose from the blood and it stimulates the liver to store glucose, which leads to a reduction in blood glucose levels. The liver is the storehouse of glucose, which it stores in form of glycogen.
• Glucagon is produced by α-cells in the pancreas and released both in response to low blood glucose levels and when the body requires additional energy (e.g. physical activities and intense stress). It stimulates the liver to release stored glucose to increase blood glucose levels.

Insulin is important to prevent hyperglycaemia, a condition of excess blood glucose. Hyperglycaemia may increase the risk of developing diabetes. In contrast, glucagon prevents hypoglycaemia, the condition of not having enough blood glucose in the body. Hypoglycaemia can lead to seizures and loss of consciousness.

The different types of diabetes

Type 1 diabetes

As symptoms are very similar, it sometimes requires extensive laboratory tests to differentiate between type 1 and type 2 diabetes.

Type 1 diabetes is caused by people’s immune system, which attacks and permanently disables the β-cells in the pancreas so that they can no longer produce insulin. The majority of people develop this type of diabetes as children or adolescents. The initial trigger is unknown. People with type 1 diabetes are not able to produce any insulin at all.

Type 2 diabetes

The vast majority (90–95%) of people with diabetes suffer from type 2 diabetes. Type 2 diabetes does not cause specific symptoms for several years and approximately 50% of people with diabetes remain undiagnosed at any time. Initially the pancreas is able to produce higher levels of insulin to counteract this resistance; however, as the disease progresses the β-cells become exhausted and start to fail.

There are several risk factors that may increase the risk of developing type 2 diabetes, such as:

• Lack of physical activity
• Obesity: more than 90% of people with type 2 diabetes are obese.
• Unhealthy diet, such high consumption of fat and sugar as well as low intake of fibre
• Smoking
• Family history of type 2 diabetes
• Older age

Although there are genetic factors which increase the risk of developing type 2 diabetes, lifestyle and behavioural factors appear to play a more important role.

Prediabetes

In people with prediabetes, blood glucose levels are higher than normal but not high enough to be classified as diabetes. Prediabetes has the potential to develop into type 2 diabetes. People with prediabetes have one of the following characteristics:

• Impaired glucose tolerance: Obesity has been shown to make cells less sensitive to insulin, which means they become insulin-resistant and do not take up glucose as normal. However, not all people with obesity develop type 2 diabetes. As long as the pancreas is able to produce increased levels of insulin to compensate for the resistance, blood glucose levels remain normal.
• Impaired fasting glycaemia: Normally, the pancreas constantly produces a low level of insulin regardless of food intake. If the pancreas is unable to produce normal levels of insulin, blood glucose levels are higher than normal during fasting.

Gestational diabetes

Gestational diabetes is a temporary form of diabetes which is associated with increased blood glucose levels in women during pregnancy. The blood glucose levels are higher than normal, but below diabetic levels. This type of diabetes usually disappears after giving birth. Factors that may increase the risk of developing gestational diabetes include excessive weight gain during pregnancy and a family history of diabetes.

Other types of diabetes

There are several other types of diabetes, such as:

• Neonatal diabetes, which may occur in children within their first 6 months of life.
• Diabetes related to other diseases, such as cystic fibrosis.
• Post-transplantation diabetes, which may occur in people following an organ transplant procedure.

Diabetes – available treatments

The main goal of diabetes treatment is to enable people’s blood glucose levels to be kept under control, getting neither too high nor too low.

Type 1 diabetes

People with type 1 diabetes, who cannot produce their own insulin, require insulin treatment. Insulin is often injected under the skin (subcutaneously); however, it is also available in powder form for inhalation. Most people inject insulin in the stomach region either with a prefilled syringe or a prefilled pen.

There are different types of insulin available, which differ in the duration of effect:

• Short-acting
• Intermediate-acting
• Long-acting

People with type 1 diabetes require low levels of long-acting insulin (basal insulin) to compensate for overnight glucose production by the liver, and for providing stable blood glucose levels throughout the day. Additional short- or immediate-acting insulin is required to keep blood glucose levels stable after meals. If too much insulin is dosed, it can lead to hypoglycaemia. To help people know how much insulin to use to avoid their blood glucose levels going too high (hyperglycaemic) or too low (hypoglycemic), they must self-monitor their blood glucose levels on a regular basis every day.

Alternatively, insulin pumps can be used to regulate the blood glucose levels throughout the day. They work by constantly monitoring the blood glucose concentration and dosing exactly the right amount of insulin to keep it at normal levels. However, the pump needs to be attached to the body at all times and there is therefore a higher risk of infections compared with prefilled syringes and pens.

Type 2 diabetes

Initial therapies include lifestyle changes, such as healthy eating and exercising in order to lose excess weight. If this does not lead to improved blood glucose levels, physicians will prescribe medication.

Any treatment of people with diabetes should be highly individualised, depending on existing diseases/problems. A selection of currently available medications can be found below:

• Metformin (biguanide) is the most commonly used type of medication to control blood glucose levels. It reduces glucose release from the liver.
• Sulfonylureas and meglitinides stimulate the pancreas to produce more insulin.
• Thiazolidinediones (TZDs) improve glucose intake into the cells and reduce glucose release from the liver.
• Glucagon-like peptide 1 (GLP-1) analogues mimic GLP-1, a key hormone in the gut that regulates blood glucose by stimulating insulin production in the pancreas and by reducing the appetite. The effect of GLP-1 is glucose-dependent, which means it has a high effect when glucose levels are high and a low effect when glucose levels are low, thereby reducing the risk of hypoglycaemia.
• Dipeptidyl peptidase 4 (DPP4) inhibitors slow down the effect of DPP4, which inhibits GLP-1.
• Sodium-glucose co-transporter 2 (SGLT-2) inhibitors prevent reabsorption of glucose filtered in the kidneys, thereby increasing the level of glucose in urine.
• α-glucosidase inhibitors delay digestion and slow down the glucose intake into the blood; however, they don’t prevent increased blood glucose levels.
• D2-dopamine antagonists mimic the hormone dopamine, which is released from the brain to regulate blood glucose.

Many people with type 2 diabetes require a combination of several different types of medications over time. Insulin treatment is used if blood glucose levels are high despite other type 2 diabetes medications.

Diabetes type 2 is often preventable

People with type 2 diabetes have a variety of different medication types available. However, it is often a preventable disease. Even people with diabetic risk factors (prediabetes) can significantly reduce their chances of developing diabetes by the following lifestyle changes:

• Having a healthy diet
• Exercise/physical activity
• Keeping weight under control/weight loss
• Stopping smoking

Diabetes – a life-changing disease

Despite available treatments, diabetes is a life-changing disease that can severely affect several different parts of the body. Diabetes awareness events, such as the current diabetes awareness week, are important to educate people about the health risks associated with diabetes and highlight the importance of a healthy diet and physical activity.

Susanne Ulm is a Medical Writer part of our Prime team at Prime Global and has been with the company since November 2014. Susanne has broad experience in different therapeutic areas, and has a passion for communicating science to different types of audiences.