Diabetes: A 21st Century Global Challenge

December 11, 2013

MELBOURNE, Australia — Type 2 diabetes will remain one of the greatest challenges to healthcare systems around the world for many years to come, experts told the International Diabetes Federation (IDF) World Diabetes Congress 2013 here last week. The condition currently affects 382 million people worldwide, a figure that is predicted to rise to almost 600 million by 2035, and 80% of the disease burden is now in low- and middle-income countries, most of whom are ill-equipped to respond to this epidemic.

These stark numbers are detailed in the latest IDF Diabetes Atlas, released to coincide with the Melbourne meeting. The map reveals that almost 50% of all people with diabetes in the world currently live in just 3 countries: China, India, and the United States, and "it's clear that in each of these countries, there will be substantial increases over the next couple of decades," Paul Z. Zimmet, MD, from the Baker IDI Heart and Diabetes Institute, Melbourne, Australia, told a Lancet and Lancet Diabetes & Endocrinology symposium at the congress.

Following these 3 nations, the remaining 7 to make up the top 10 are: Brazil, the Russian Federation, Mexico, Indonesia, Germany, Egypt, and Japan, illustrating that the epidemic is reaching all corners of the globe, said Dr. Zimmet.

Critical Issues in Diabetes Development

There is much to consider, he said. First, new research on diabetes epidemics in countries that have previously experienced famine indicates that epigenetics has a big role to play in development of the disease, and this has implications for future prevention in countries currently experiencing such disasters, he noted.

And the emergence of type 2 diabetes in youth means "the burden of diabetes will mainly fall on the working-age group in developing countries, which has huge health and economic consequences," he noted, adding that a high percentage of people in those countries are undiagnosed.

"The cost of diabetes and its complications is clearly something we have to be concerned about," he stressed. "In 2010, the global cost was $376 billion, about 20% of all healthcare costs. Even in lower-cost areas, these costs from diabetes can cripple economies through the health costs and the economic costs due to loss of national productivity, etc," he observed.

Also disproportionately affected are indigenous populations all over the world, Dr. Zimmet explained, with this phenomenon first observed among the Maoris in New Zealand and the Pima Indians in Arizona. To help address this, the IDF World Diabetes Congress featured, for the first time, a whole conference track specifically dedicated to "diabetes in indigenous peoples."

Other doctors speaking at the symposium detailed separate issues, all covered in papers simultaneously published in special issues of the Lancet and Lancet Diabetes & Endocrinology, entitled "Managing Diabetes in the 21st Century."

Steven E. Kahn, MD, from the VA Puget Healthcare System and University of Washington, Seattle, discussed the pathophysiology and treatment of type 2 diabetes, with perspectives on the past, present, and future.

One of the "critical" questions still unanswered, said Dr. Kahn, is whether to institute sequential therapy with metformin for diabetes, followed by another medication when that fails to adequately control diabetes, or whether to go in initially with combination therapy. Also, the ideal "second" drug to use after metformin is still not known, he said, highlighting the GRADE study, which has just begun and will attempt to answer that question.

And Leif Groop, MD, from the University of Helsinki, Finland, spoke about the "many faces" of diabetes, which is rapidly being recognized as a disease with increasing heterogeneity. The present subdivision into types 1 and 2 probably represents extremes on a range of diabetic disorders, he said. It is hoped that better characterization and delineation of these many subgroups will assist in the individualization of therapy in the future, Dr. Groop concluded.

Mauritius: Global Microcosm Sees 62% Rise in Diabetes

Dr. Zimmet began his talk by discussing Mauritius, a small country with a triethnic population of black Creoles of African origin, Chinese, and Asian Indians, which "together constitute 66% of the world's population" in terms of ethnicities, he said.

He and his colleagues have studied diabetes there for many years, and he explained that "Mauritius is a microcosm of the globe in the sense of the ability to predict future trends." The prevalence of diabetes there has risen from 14.6% in 1987 to 23.6% in 2009, equally in each of the ethnic groups, and this represents a 62% increase in diabetes during that time, he observed.

"On the basis of these trends in these 3 different ethnic groups, we are predicting that in China, India, Africa, and anywhere in the diaspora where these people have migrated to we will see higher rates of diabetes eventually."

Indeed, this has come to pass in China, he noted, which had a prevalence of diabetes of less than 1% in 1980, but "the latest studies [2009] show an almost 10-fold [increased] prevalence over these 29 years. The number of people predicted to have diabetes in China at present is in the vicinity of 114 million." And there are also "huge" rates of prediabetes there, he added, noting, "This is confirmation of what we all expected, and that was that things would change in China."

Another area of great concern is the Middle East and North Africa, where 1 in 10 adultshas diabetes.

Dr. Zimmet then went on to discuss whether there have been any falls in diabetes rates. This has occurred, but rarely, "in World Wars I and II in Europe, and a recent report in the BMJ indicates a fall in diabetes rates in Cuba," he noted. And diabetes cases in Nauru, a small Pacific Island nation that previously held the title of the highest rate of diabetes in the world, have plummeted.

"There is clear evidence in Nauru that there has been a secular decrease, which seems to correspond to very poor economic circumstances, [during which] the Nauru economy collapsed," he explained.

All of this research sets the backdrop in trying to understand diabetes and its causes and thereby help prevent future epidemics, he noted.

The Role of Famine in the Global Diabetes Epidemic

Important new research on the developmental origins of diabetes in the past few years indicates that regions previously less affected could see big rises in cases of the condition in years to come, Dr. Zimmet told the meeting.

Major increases in type 2 diabetes have occurred in the offspring of starving mothers in Holland, China, and Cambodia 40 to 50 years after serious famines, indicating that something is occurring during the mother's pregnancy that might affect the fetus's likelihood of chronic disease in adult life.

"A child in the womb during a period of under- or malnutrition has an expectation, when he or she emerges, that they will arrive into the similar situation of famine, but these days they hit an obesogenic environment, and 30 to 40 years later they experience a much higher risk of type 2 diabetes," he explained.

There is now substantial evidence that epigenetics — processes that produce heritable changes in gene expression without altering the gene sequence — play a role and lead to human diseases such as type 2 diabetes.

"It's pretty well established that there are a number of risk factors during a mother's pregnancy that can cause epigenetic changes in the fetus, including smoking, alcohol, malnutrition, hypertension, and gestational diabetes. Animal data show that these changes are intergenerational, so we can create a vicious cycle of type 2 diabetes going through a number of generations."

This "story" also has significance when it comes to future prevention of this disease, Dr. Zimmet explained, with earlier intervention needed, at the time of fetal programming.

"Those who cannot learn from history are doomed to repeat it. There are a number of nations, particularly in the Horn of Africa, that are experiencing famines at the moment. This raises the possibility of future hotspots of diabetes in regions that have droughts and famines at present, if economic and living conditions improve within the next few decades.

"We've shown we can prevent diabetes in high-risk people in studies in the US, in India, in China, and in Japan, but we are not getting to the masses," he stressed. "Attention must be directed to establish which countries in the future may bear the brunt of diabetes and make them regions of priority for prevention," he concluded.

Dr. Zimmet and coauthors have reported no relevant financial relationships. Dr. Kahn has received honoraria for advisory work and lectures from Boehringer Ingelheim, Bristol-Myers Squibb, Elcelyx, Eli Lilly, Genentech (Roche), GlaxoSmithKline, Intarcia, Janssen, Merck, Novo Nordisk, Receptos, and Takeda. Disclosures for the coauthors are listed in the article. Dr. Groop has reported no relevant financial relationships. Disclosures for the coauthors are listed in the article.

Lancet. Published online December 3, 2013. Kahn abstract, Groop abstract

Lancet Diabetes Endocrinol. Published online December 3, 2013. Zimmet abstract

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