SUGAR, FAT, ENERGY AND INSULIN

Diabetes is a disorder that affects the body's ability to store and use the energy required for life. Glucose (a “simple sugar”) is the main chemical form in which the body transports energy via the blood to the body parts where it is needed (brain, muscles and so on). A persistently raised blood sugar level is the main indicator of diabetes.

The liver (the body's principal chemical factory) is the main source of circulating glucose, whose level is tightly regulated in response to food and energy needs.

Nutrients from food are absorbed through the intestine and pass via the portal vein to the liver, where they are converted into glucose, which is then released into the circulation.

Excess energy is stored in the liver and muscles in the form of glycogen, which is made from glucose. Glycogen can easily be broken down to glucose again when needed. More importantly (as the capacity to store glycogen is limited), excess glucose is converted into fat (lipid), which is stored in fat cells in adipose tissue (body fat), and in the liver and muscles.

Glucose formation, release and utilisation is regulated by the hormone insulin, which is made by the beta-cells of the pancreas. Insulin secreted from the pancreas passes via the portal vein into the liver, where it controls the production of glucose, either from the breakdown of stored glycogen or from the formation of new glucose. When glucose levels in the blood rise following a meal, insulin secretion rapidly increases and shuts down the production of glucose by these two processes.

Insulin has a second important function in glucose regulation. It acts on muscles to cause uptake of glucose from the circulation into muscle cells, where it is stored as glycogen or burned to provide energy. Insulin also stimulates fat cells to take up glucose and convert it into a type of fat (triglycerides) for storage.

Fat cells release many molecules into the circulation, including signalling molecules that interfere with the action of insulin, causing insulin resistance. Veins from fat cells deep in the abdomen join the portal vein and drain into the liver, providing a direct route for products of fat cells to affect it. The liver is the body's main site for glucose storage and production.

Insulin resistance is strongly linked to obesity. It reflects the number and activity of the fat-storing cells in body fat, particularly those located deep in the abdomen and in the liver and muscles.

When things go wrong

Biochemical changes in glucose regulation can be detected long before clinical symptoms become noticeable. For example, insulin resistance or reduced insulin output can be shown years before type 2 diabetes is diagnosed, and in such cases a “pre-diabetic” state may be said to be present. This may be shown either as a raised blood glucose level between meals, or as a reduced ability to clear glucose from the circulation quickly and completely (impaired glucose tolerance - IGT).

Problems with blood glucose control may develop in a number of ways. A failure to produce insulin, because of so-called autoimmune destruction of the beta cells in the pancreas, lies at the heart of type 1 diabetes. By contrast, the root cause of type 2 diabetes is thought to be the loss of a response to insulin (onset of insulin resistance) in the liver and muscles, followed by toxic effects of high blood glucose and lipid levels that may damage pancreatic beta cells.

Persistently high blood sugar levels in diabetes (hyperglycaemia) and other unfavourable changes, such as raised blood pressure
(hypertension) and altered blood fat content (dyslipidaemia), lead to damage to organs such as the kidneys, nerves, retina and blood vessels, resulting in serious and costly complications (nephropathy, neuropathy, retinopathy and cardiovascular disease). Damage is also thought to be caused by activation of the immune system (low-level inflammation).

Diabetes is treated with medicines that:

• provide insulin that is missing
• increase its production by the pancreas
• improve its efficiency in working (improve insulin sensitivity)
• prevent or ameliorate the development of complications by reducing other risk factors (such as high blood pressure) or harmful biochemical changes.

Other approaches, such as making changes to food intake/composition and exercise, are vitally important and must be undertaken as well as treatment with medicines. Such lifestyle changes can be as beneficial as medicines, but may be difficult to sustain in the long term, as they require permanent changes to daily habits. However, exercise can have dramatic effects in improving insulin sensitivity, and reducing obesity and changing eating habits can both reduce obesity and the extremes of blood sugar variations that may be damaging in diabetes.