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Bitter Melon

A trial is about to start in the UK in 500 gay men who regularly have unprotected sex or are involved in heavy drug use to determine if the drug Truvada will prevent the HIV infection.

Diabetes kills more people worldwide than HIV, tuberculosis and malaria combined so why are we not trying to prevent its development?

According to the International Diabetes Federation there are some 382 million diabetics in the world with 90-95% having Type 2 diabetes. If unchecked this is predicted to rise to 592 million by 2035.

Diabetes is a silent disease in the early stages and typically the patient has had the disease for many years before diagnosis. Around 80% of the world’s diabetics live in low or middle income countries and 50% of the world expenditure on diabetes treatment occurs in North America.

Type 2 diabetes results from a combination of resistance by glucose consuming tissues in the body to insulin and inappropriate insulin secretion by the insulin producing cells in the pancreas. Because of the resistance to insulin action, islet cells release more insulin to compensate. This over-production leads to progressive failure of pancreatic islets. It is estimated that at the time of diagnosis most patients have lost up to 70% of their insulin producing cells. At a 90% loss, the patient can no longer produce sufficient insulin and will require exogenous insulin by injection. Consequently, there is only a small treatment window for oral agents.

Treatment focus

A sensible treatment of diabetes would focus on preserving pancreatic islet cell function for as long as possible. However, treatment today is glucose-centric and the most common treatments of metformin and sulphonylureas are only effective in lowering blood glucose for a short period and do not preserve islet cell function. Indeed, some studies suggest sulphonylureas may actually accelerate the rate of islet cell failure.

Recent research has suggested a new direction for treatment focusing on the pathophysiology of diabetes and to both produce durable control of blood glucose and preservation of islet cell function. It is suggested that this might require three drugs used in combination – metformin, an insulin sensitiser drug such as pioglitazone or rosiglitazone and a GLP-1 agonist or an agent that enhances endogenous GLP-1 responses. Clearly such a regime is only going to be affordable in high income economies.

An alternative approach

Is there another way? Could we detect patients who are likely to develop diabetes and look at prevention? How could we do this and what could be used for prevention of the development of diabetes?

As a starting point we could use a glucose tolerance test (as used in pregnancy) in all subjects that were obese or overweight. However, hyperinsulinaemia is one of the major characteristics of the early stages of Type 2 diabetes and a focus on measuring insulin would be a major advance. The problem is that current tests are expensive and a test is required that is cheap and reliable and could be conducted in a primary care or through a national screening programme. Why can we not have routine screening vehicles visiting communities in the same way that we screen for breast cancer?

If we were able to diagnose pre-diabetes, how could we treat it? Studies in the United States have shown that insulin sensitiser drugs are able to either delay the progression to diabetes or even revert pre-diabetic subjects to normal. Adding metformin gives additional benefit. However, would such treatments be affordable in lower and middle income countries and even if affordable would the risk-benefit be acceptable? The two insulin sensitiser drugs used in the US studies, pioglitazone and rosiglitazone, have the side effects of water retention and weight gain and although the earlier claims of serious cardiac disease arising from rosiglitazone treatment has now been found to be invalid, neither drug should be used in heart failure patients.

Plant-based solutions?

The answer to the dilemma might be in using plant-based treatments. Such treatments could be more acceptable to both higher income and middle and lower income economies. The most commonly used drug, metformin, was originally derived as a result of the anti-diabetic properties of French lilac and dates from 1929. The edible gourd bitter melon, Momordica charantia, appears to have very similar activity to metformin in animal studies. Could we combine this with an edible plant that had insulin sensitiser properties to give a combination of properties that might provide an acceptable mixture that could delay or even stop the progression of pre-diabetes to diabetes? There are indications that such substances exist but more research is needed.

Mike Cawthorne

Professor Mike Cawthorne heads the Institute of Translational Medicine at the Clore Laboratory, University of Buckingham and heads the Medical School that will take its first MB ChB students in January 2015. Mike led the research team that discovered rosiglitazone and declares he holds shares in GlaxoSmithKline.

Mike Cawthorne
Director of Metabolic Research and Head of Medical School
Clore Laboratory
University of Buckingham
tel: +44 (0)1280 820309
[email protected]
www.buckingham.ac.uk/bitm