Type 2 diabetes occurs because some people cannot respond normally to the insulin they make (unlike type 1 diabetes which is characterised by the body not producing enough insulin). This results in high concentrations of glucose in the blood, which can damage many of the body’s systems, especially blood vessels and nerves.

Insulin is an important hormone made in the human pancreas – a small organ that sits close to the intestine. Insulin regulates the body’s use of glucose (sugar), which is one of our major energy sources. Insulin is particularly important after we eat a meal when glucose enters the blood stream from the intestine. The elevation in blood glucose at this time triggers the release of insulin from the pancreas. Insulin then travels through the blood and assists the transfer of glucose from blood into cells so it can be used for energy.

There is now evidence of an underlying genetic predisposition for type 2 diabetes, with some genes consistently associated with an increased risk of developing the condition. The inability of the body to utilise glucose (insulin resistance) is strongly correlated with waist measurements and abdominal fat levels. Garvan’s research shows that fat directly around organs in the stomach, rather than fat under the skin, is a major risk factor. If left untreated, diabetes can cause serious long-term complications including kidney disease retina damage, cardiovascular disease and nerve damage, often resulting in amputation.

You are in a high-risk category of developing type 2 diabetes if you fit any of the following criteria:

• Over 45 years of age, overweight and/or have a high blood pressure
• Over 45 years of age and have a family member with diabetes
• Have heart disease or have suffered a heart attack
• Have/had high blood glucose levels or have impaired glucose tolerance
• Have/had gestational diabetes
• Are overweight (i.e. have a Body Mass Index higher than 25)

Type 2 diabetes develops gradually, so sometimes symptoms often go unnoticed. These may include frequent urination, thirst, blurred vision, skin infections, slow healing, tingling and numbness in the feet. Sometimes no symptoms are noticed at all or the individual assumes that they are part of the normal ageing process. Either a Fasting Blood Glucose (FBG) or Oral Glucose Tolerance Test (OGTT) ordered by a doctor, are used to make a diagnosis.

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The first recommended action for someone with type 2 diabetes is to reduce their body mass index. This may involve taking weight loss medication. Increased exercise and a healthy diet can prevent the more serious health problems that often occur in people with diabetes, such as heart disease, stroke, high blood pressure, circulation problems, nerve damage, and damage to the kidneys and eyes. The appearance and severity of these complications is dependent on the duration of type 2 diabetes and can be delayed or even prevented by early detection and treatment.

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Garvan’s diabetes researchers aim to identify the molecular mechanisms underlying the condition and are tackling the problem through the use of genetic approaches, animal models, and clinical studies.

We now know that there are many genes involved in the development of type 2 diabetes and they may trigger the disease only if there is a strong environmental influence. We are conducting a series of DNA studies on human abdominal fat samples to find the key genes involved in the body’s inability to process glucose (insulin resistance). There are proteins in our cells that receive and transmit messages to and from other cells. Garvan scientists isolated & showed that one of these proteins PKC is a key player in regulating removal of glucose from the blood. When PKC is blocked, the body is protected against the development of a prediabetic condition, despite fat consumption and low levels of physical activity.

An array of molecular and clinical studies have allowed us to establish that the generalised inflammation in people with type 2 diabetes, which contributes to the increased risk of cardiovascular disease, is not present in pre-diabetes; findings that allow us to gain insights into the steps involved in diabetes development.

Other Garvan scientists are working in collaboration with colleagues at the Shanghai Institute of Biological Sciences to study the effects of Chinese herbal medicines on the treatment of type 2 diabetes, and scientifically investigate the effect of key plant compounds. Our global approach to tackling diabetes is highlighted by our role in establishing an Asia Pacific diabetes and obesity study group to facilitate researcher interaction and greater outcomes for consumers.

Yet another discovery at Garvan is a genetically engineered mouse that eats more without gaining weight. As a result of having less fat, the mouse also displays enhanced insulin action and an improved ability to process blood sugar, making it more resistant to type 2 diabetes. This finding provides a new avenue for the discovery of compounds that would allow people to eat more without gaining weight, by converting food to energy instead of storing it as fat. It also enables us to develop new approaches to address our genetic risk factors as well as the better-known environmental ones.

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