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*On the trail of the world’s formidable epidemic*
By JUDY SIEGEL-ITZKOVICH
06/01/2014
Australian diabetes researcher Prof. Paul Zimmet, who has visited Israel over 30 times in five decades, has earned an honorary doctorate from Tel Aviv University in recognition of his life work.
 
The Israeli sand rat, which thrives in the Negev and is an excellent model for the study of type 2 diabetes and obesity, is a favorite of Prof. Paul Zimmet – one of the world’s leading researchers into the disease who predicted almost a quarter of a century ago that it would become a worldwide epidemic.

Although they are native to other parts of the Middle East and North Africa, those from the south of Israel have been most extensively raised and studied here and elsewhere (although the US refused to allow them in for fear that they would spread parasitic disease). Zimmet himself studied the sand rats for 15 years.

Unlike other small rodents, this species is active during the day and can easily acquire diabetes when they are fed a normal laboratory diet of grains. This type gerbil has very efficient kidneys, surviving the blistering heat of the desert with little water and producing very concentrated urine. As they can get depressed when there is less light, they are also useful for studying the widespread seasonal affective disorder (SAD).

Zimmet, who has visited this country over 30 times since 1965, recently received an honorary doctorate from Tel Aviv University, handed to him by its president, Prof. Joseph Klafter.

The honor was bestowed on him “in recognition of his contribution to world medical progress as a foremost expert in diabetes mellitus; his illustrious career as scientist, educator, physician and public health leader, for which he has been recognized in his native Australia and internationally; his tireless efforts to raise awareness of diabetes as a global health emergency and shape the health policy response; his prolific published works related to diabetes, obesity and the metabolic syndrome; his extensive public service record, including his roles at the World Health Organization, the International Diabetes Federation and, most recently, as chairman of the World Diabetes Congress.”

Klafter also cited Zimmet’s “outstanding collaborative research with Israeli scientists in the genetics of diabetes and obesity, which has led to the identification of new genes associated with diabetes; and his generosity, together with his wife, Vivien, in establishing and supporting for over two decades the very first fund dedicated to rewarding excellence in diabetes research at Tel Aviv University.”

Zimmet, who is director-emeritus of the Baker IDI Heart and Diabetes Institute in his native country, spent 15 years studying diabetes in the fat sand rat and has been in touch with TAU zoology Prof. Noga Kronfeld- Schor and her colleagues on SAD research on the furry little rodents. He is planning joint research with colleagues at TAU on why diabetics have a higher prevalence of depression.

Zimmet established and for years directed Australia’s International Diabetes Institute, his country’s first research center devoted exclusively to the disease. Now an emeritus professor, he was appointed to the Australian government’s executive committee for the prevention of type 2 diabetes and its prevention task force for obesity, tobacco and alcohol.

He has been amazingly prolific during his long scientific career, published more than 800 scientific papers, chapters and reviews in peer-reviewed journals and books. He also co-edited two major texts, the International Textbook of Diabetes Mellitus and The Epidemiology of Diabetes.

Captivated by a 1965 medical journal article by a New Zealand epidemiologist about a high prevalence of diabetes among Pacific islanders, in 1955, Zimmet flew seven hours from Melbourne to the isolated island of Nauru, where he tested the indigenous Micronesian population. On just day one of his research, he tested 100 residents and and found that one-third of them suffered from diabetes.

Originally, they had consumed a healthful diet, but when they became sedentary, ate processed fatty and sugary foods and gained weight, their metabolic system was unable to cope. “After years of modernization, the residents of Nauru had 5 times the diabetes levels as the general population in Australia.”

When Zimmet, who gave an interview to The Jerusalem Post during his latest visit to Israel, understood the implications of a traditional people who became Westernized, he predicted the world “diabesity” epidemic.

Borrowing the term ”coca-colonization,” he suggested then that by now there would be 200 million people with diabetes; in fact, it has nearly reached 400 million.

Zimmet now estimates that by 2035, which is little more than two decades away, the number of type 2 diabetes in the world will reach 600 million. The financial costs to the world’s health systems are already prohibitive, but in a few decades, it could cause economies to collapse.

“Diabetes is likely to be the biggest health problem, the largest epidemic in human history,” he said. Yet it is not inevitable, as patients in the pre-diabetes stage when their metabolism has veered from the normal can prevent its development into disease by exercising, losing weight and eating right.

He led Australia’s first national study on diabetes and obesity – the AusDiab Study – the first national diabetes and obesity study in Australia and one of the largest national diabetes research project in the world.

A more recent finding is that type 2 diabetics also have a higher risk of sleep apnea. This condition, in which there are pauses in breathing or shallow breathing for at least 10 seconds during sleep, can lead to inadequate oxygen and excessive carbon dioxide in the body. Although the sufferer is rarely aware of these episodes, they suffer from them by feeling chronically sleepy during the day and slow reactions that could lead to work and road accidents. However, if the problem is identified in a sleep lab, it can be treated with CPAP (continuous positive airway pressure) devices worn during sleep to pump air into the lungs. “I am doing a new collaboration with Noga Kronfeld,” said Zimmet. “About 40 percent of diabetics have sleep apnea or are at high risk of it. Overweight is one factor, but there is an independent association even in lean people.”

ZIMMET WROTE about his family’s past in an article published five years ago in the Medical Journal of Australia.

Called “The Power of One,” the article begins with his father Jacob in the small Polish town of Tarnopol. He studied medicine in Vienna and graduated in 1935. Realizing that as a Jew he had no future in his native country, Jacob applied for a visa to Australia and the US two years later.

The Australian visas were the first to arrive. His mother Anna was so reluctant to leave that she considered burning the documents. But Jacob persuaded her, and in the nick of time, in December 1938, they and their daughter Rena sailed for Sydney, Australia and arrived a month later. In September, World War II broke out.

Since Jacob’s medical degree was from Austria, it was not recognized by the Australian authorities because it was earned under Nazi occupation, and he had to requalify. The family moved to Adelaide because there it would take him just three years to earn his MD degree. Paul was born in 1941 in the small Jewish community of Adelaide. In 1966, Paul settled in Melbourne to “find A Jewish bride.”

One of the reasons why he and Vivien have come so often to Israel is that her late uncle, Aaron Gutwirth – who owned Champion Motors – died and left his money to the Gutwirth Foundation, which provides academic and research scholarships. So we’ve had a long association with this country. My Hebrew, though, is still from my bar mitzva.”

Zimmet had thought of going into general practice, “but the only job I could get in Melbourne so he could stay and court his future bride was at the diabetes unit at Alfred Hospital, a large one with 1,500 beds.”

There he completed a clinical residency in diabetes while treating patients suffering from ketoacidosis, a pathological metabolic state involving high concentrations of ketone bodies formed by the breakdown of fatty acids. He was then sent to do a doctorate at Monash University in Melbourne in the Australian state of Victoria.

“In 2000, my colleagues and I did the first Australian national obesity study – that found 60 percent of the population were overweight or obese and 7.5% of adults had diabetes. Now it has probably reached 65%, not far below America’s rate of 70%.” He noted that the diabetes rate among Indigenous Aborigines in Australia is four times higher than the general population.

Zimmet wrote an editorial on bariatric (weight-loss) surgery and diabetes two years ago in the prestigious New England Journal of Medicine (NEJM). In bariatric surgery, the capacity of the stomach is reduced with a gastric band, by cutting out part of the stomach or by resecting and re-routing the small intestines to a small stomach pouch. Amazingly, bariatric surgery can much improve and in 70% to 80% of cases even reverse diabetes in the obese. Bariatric surgeons thus claim that they can treat the metabolic condition better than physicians who give pills or insulin injections.

Zimmet explained that “the re-plumbing of intestines raises the level of a hormone called incretin, which improves pancreas’s ability to make insulin. Amazingly, while the lap band works for diabetics by helping them to lose weight as they have less room to digest food, gastric surgery to make the stomach smaller starts improving diabetics’ blood sugar control within a few hours.”

There are studies in Asia showing that bariatric surgery works even in people who are not overweight, “but i wouldn’t recommend it. It is very drastic. To have an operation, you need very good medical indications,” he insisted.

The doctor/scientist noted optimistically that if diabetics control their blood sugar, blood pressure and blood fats, and if they exercise and maintain normal weight, “They should live an almost-normal lifespan.

Treatment today is much better than it was.” Yet, unfortunately, 40% to 50% of patients are not adequately controlled, and diabetes in the developing world “is a disaster.”

He testifies to his eating “a reasonably healthy diet like vegetables and chicken. I ride a bike and jog nearly every day. Like most people, I believed that obesity and diabetes were due solely to lifestyle. But there is research now showing that what happens to the baby in utero may cause epigenetic changes [heritable changes in gene activity that are not caused by changes in the DNA sequence] that can result in diabetes.”

As a result, Zimmet believes that one can prevent type 2 diabetes not only in adults or children but through maternal healthcare.

“Breastfeeding appears to have a positive effect on reducing risk. Pregnant women need better advice. Certainly, they should not smoke or drink alcohol. Chemical changes in the DNA don’t smoke, don’t drink alcohol. Chemical changes in the genes are intergenerational.”

The resultant infant grows up and herself becomes a mother, and the changes can develop into a vicious-cycle type 2, causing diabetes in the next generation. He recalls that a famine in China in the late 1950s led to epigenetic effects on babies born at that time leading to the development of diabetes 40 to 50 years later in adult life when the population began to eat a more Western diet. There are now 120 million diabetics in that country.

Hearing that an Israeli company, Oramed, is working on an oral insulin pill, Zimmet said that “we are still a long way off from such a wonderful thing, but I wish them luck. One of the problems is ensuring that the insulin survives the digestive system, but also that you are getting the right amount. With an injection or a pump attached to a vein, you know more precisely how much insulin you get.”

Although insulin was discovered only in 1921, the condition was recognized much before that. He noted that Jewish sage and physician Maimonides (the Rambam, who was born almost 900 years ago) “was one of first people to describe diabetes in his writings. He was a very wise person.”
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