E-commentary: The Silent Epidemic

What does King Fadh of Saudi Arabia have in common with the rock star Meat Loaf?

Both frequently urinated, had insatiable thirsts, were often tired and always wanted to eat. In addition they both probably were irritated by itchy feet and blurred vision. Symptoms shared by the Lord Kennedy of Southwark who, in a 2011 House of Lord’s debate, admitted that, “For many years I felt stressed, agitated, tired and run down.” King Fahd, Meat Loaf and the Lord Kennedy all suffered from diabetes, the silent epidemic.

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycaemia resulting from defects in insulin secretion, insulin action or both. The disease has been recognized for more than 3,500 years, since its early description in 1552 BC in Papyrus of Ebers from Egypt. Type 1 diabetes is an absolute deficiency of insulin secretion, which results from the body’s immune system attacking insulin producing islet cells. Type 2 diabetes results from a combination of resistance to insulin action and inadequate insulin release. About 95% of the incidence of diabetes is Type 2, which is strongly associated with obesity and lack of physical activity. Another type of diabetes is called gestational diabetes, which occurs in pregnancy and shares similar features to Type 2 Diabetes.

The non-dramatic, insidious and chronic nature of the major form of diabetes masks the fact that it has become a global epidemic with the potential to overwhelm national health systems if nothing is done to halt its progress. More worrying, is the fact that Type 2 Diabetes is strongly associated with other chronic diseases such as high blood pressure, stroke, heart disease and high cholesterol. It is “a strange world” said the Lord McColl of Dulwich in the 2011 parliamentary debate: “Half the world is dying of starvation; the other half is gorging itself to death.In the United Kingdom there are over two million people suffering from diabetes as a result of obesity . . . . . diabetes has reached epidemic proportions and now affects teenagers and young children. Parents seem to be unaware and unconcerned that their children are obese.”

Lord McColl’s sentiment is echoed in a 2012 World Health Organization Report: between 1980 and 2008 obesity doubled and today 0.5 billion people, 12% of the world’s population, are obese, which is a leading cause of Type2 diabetes. Currently, over 347 million people worldwide have diabetes; an estimated 3.4 million people died from diabetes in 2004 and by 2030 diabetes is expected to increase by 150% in developing countries. Research, predicated on 30 years of data from 200 countries and regions and published in The Lancet in July 2011, confirms that the prevalence of diabetes has reached epidemic proportions worldwide despite the fact that the disease and its complications can be prevented by a healthy diet and regular physical activity. Both studies predict a huge and escalating burden of medical costs and physical disability as the diabetes increases a person’s risk of heart attack, kidney failure, blindness and some infections.

Earlier this year, a paper delivered to the American Diabetes Association at the world’s largest diabetes conference in Philadelphia, estimated the cost of diabetes, in the US alone, to be over US$174 billion and by including gestational and undiagnosed diabetes, the cost could exceed US$218 billion. Such staggering costs and the millions of sufferers represent significant drivers of research for a cure. However, the success in diabetes research has been in the treatment and a cure has been elusive. The current gold standard therapy is strict glycemic control in order to minimize complications. The therapeutic goal is normoglycemia, achieved with supplementary insulin or other pharmacological agents that either stimulate insulin release or reduce insulin resistance.

What does the future hold for a person with diabetes? Current therapies, including insulin, are not cures, but are merely palliating the consequences of defective glucose regulation. In 2011, the Lord Crisp, who has played a leading role in raising awareness about the plight of diabetes, tabled an important House of Lord’s debate, mentioned above, on chronic non-communicable diseases and argued that, “We need this debate to talk about what needs to be done to tackle the worldwide epidemic of these preventable diseases, as traditional methods of combating them are obviously no longer working.”

A potential cure for diabetes is to replace the function of defective pancreatic islets. This may be achieved directly, through islet cell or pancreas transplantation or indirectly, through a bio-artificial pancreas. Islet cell transplantation involves injecting islet cells from a donor into the liver of a patient. Usually, pancreas transplantation is achieved in the setting of a combined pancreas and kidney transplant in patients with advanced diabetes and kidney failure. In appropriate patients, both are successful options to restore normalise glucose levels in diabetic patients. However, impediments to the success of transplantation include surgical risks, costs, risks from life-long immune suppressants and eventual graft failure. Moreover, transplantation is severely limited by the relatively small number of donors compared with the demand. Over the past decade, the number of organ donors generally has increased in some developing countries. However, there are unresolved ethical and clinical issues associated with this rise in organ donors.

A promising area of diabetes research is cell engineering. This involves the generation of glucose-responsive insulin-producing cells from a diabetic patient’s own cells, which can then be implanted into the same patient without the need of donors or life-long immune suppression. However, there are significant challenges associated with this approach. From a different perspective, biotechnologists have been attempting to develop an artificial pancreas that can detect changes in glucose and deliver insulin in response to this. Although insulin pump technology has been around for many years and recently glucose sensor technology has developed significantly, there remain substantial challenges to developing a sophisticated bio-artificial pancreas that can replicate biology with the changing demands of the human body.

A successful surgical therapy for Type 2 diabetes is gastric bypass surgery. This involves changing the plumbing of the gut so that ingested food is delivered to more distal parts of the gut more rapidly after a meal. Certain forms of this surgery can have dramatic effects on improving and even completely resolving diabetes in obese diabetic patients. Although this may appear an ideal solution, surgical costs and risks cannot be ignored. Furthermore, long-term outcomes from these irreversible procedures are still unclear. Interestingly, the improvement in diabetes occurs before weight loss. This has prompted extensive research into the biological mechanisms causing improvement of diabetes following gastric bypass surgery. Gut hormones are thought to be key players in this regard. It is hoped that judicious use of a combination of gut hormones may recreate a surgical bypass using drugs without the risks, costs and irreversibility of surgery.

Although advances in diabetes research are significant, the horizon for a cure is still distant. Moreover escalating costs of delivering medical cures to increasing numbers of patients and risks associated with some of the potential options are significant hurdles. At this moment in time, the best option for a cure for diabetes seems to be prevention.

Over the last century, our genes and biology have not changed much, but our lifestyles certainly have. Changes in the way we live our lives appear to have occurred in tandem with a diabetes and obesity explosion. It is difficult to ignore the fact that this chronic non-communicable epidemic has societal and environmental origins that need to be addressed more effectively while we wait for a biomedical cure. Former FDA Commissioner David Kessler suggests that diabetes may not be an entirely self-inflicted phenomenon. In his book, The End of Overeating, Kessler warns that restaurants and food processors purposely engineer food that encourages people to overeat and ruin their lives. But, if you do not warm to conspiracy theories, think of the Chinese proverb: "He that takes medicine and neglects diet, wastes the skills of the physician.