Conference Pearls

The 19th World Diabetes Congress (Cape Town, South Africa, December 3-7)

This winter we flew down to sunny Cape Town to attend the nineteenth official meeting of International Diabetes Federation (IDF). This conference, held only once every three years, drew over 12,000 clinicians, scientists, and other attendees. Diabetes isn't easy for anyone to live with, but this meeting reminded us of how lucky we are, in the US, who have health insurance and access to the drugs and devices that make such a difference.

Diabetes is an international epidemic.

Diabetes is a global epidemic, but its greatest impact right now is in fast-growing, developing countries - the most prominent being China and India, which have more diabetic patients than any other countries in the world. About 180 million people have diabetes worldwide, a number expected to at least double by 2030, according to the World Health Organization. China had about 21 million people with diabetes in 2000 (so, likely a few million more now), which is also expected to double by 2030. India had about 32 million people with diabetes in 2000 and is expected to have 80 million (much more than double!) by 2030. These numbers compare to 15 million in the US, a number we typically perceive as sky-high. This crisis reflects these countries' emerging, industrialized economies, which are bringing increased affluence but also the dark side of prosperity: sedentary lifestyles, high-caloric Western diets, and obesity.

Highlight on diabetes in children.

In poor countries, children with diabetes are often not diagnosed until long after onset. Some die for want of a diagnosis, while others who are saved have severely shortened lives because insulin is too expensive or simply unavailable. Leading pediatric diabetes specialists Dr. Francine Kaufman and Dr. Henk-Jan Aanstoot spoke about the IDF theme for 2007: diabetes in children. We hope that passage of the UN Resolution for Diabetes will bring greater attention to this troubling area.

Obesity is not the only cause of metabolic syndrome.

While obesity, especially central obesity (fat around the stomach), undoubtedly has a role in the development of type 2 diabetes, many other factors contribute. Family history plays a big role in susceptibility to metabolic syndrome and diabetes. We also heard doctors talk about how stressful modern lifestyles and environments can activate our inflammatory responses to cause insulin resistance. Insulin resistance is one of the two "dual defects" of type 2 diabetes - the first defect is insulin secretion. In plain English, this means that type 2 patients tend to have two problems - one relates to insulin resistance and usually happens first; this means insulin can't be properly or optimally processed. The second problem comes when the body has problems with insulin secretion; it doesn't, in other words, produce enough. Obesity exacerbates both defects, so with the type 2 epidemic, it wasn't a surprise to see such a big focus on obesity. After all, it is said that if excess weight (being overweight or obese) disappeared, over 80% of type 2 diabetes would disappear.

Diabetes differs among ethnicities.

Obesity and metabolic syndrome affect ethnic groups differently. . Asians generally have more visceral fat ('bad' fat) than Caucasians, Africans, and Hispanics with the same BMI. Because visceral fat is associated with insulin resistance, this means that Asians tend to have a higher risk of developing diabetes at lower body weights. Asians are also more genetically prone to lose beta cell function, the other contributing factor in type 2 diabetes. The bottom line, though, is that people of every nationality, race, religion, age, and creed are increasingly at risk for diabetes as modern lifestyles - too much food, too little exercise - spread throughout the world.

Diabetes drugs don't last long enough by themselves.

The results were released from a big study called "ADOPT," which highlighted the fact that several common diabetes drugs stop working after a few years. The trial was designed to compare a thiazolidinedione (TZD), a sulfonylurea (SU), and metformin, when each was used by itself as the initial treatment in people with type 2. Though none of them performed outstandingly, the TZD did the best, followed closely by metformin and trailed at a distance by the SU. At four years, 40% of people on the TZD were at target A1c (below 7%), while 36% of people on metformin were at target, and only 26% of people on the SU were at target. The study confirmed what doctors generally know by now - that "monotherapy," or taking only one diabetes drug, does not really work. "Combination therapy," or taking more than one drug, seems much more effective. It produces fewer side effects as well - less weight gain on TZDs, fewer gastrointestinal side effects on metformin, and less hypoglycemia on SUs - because each drug does not need to be at its maximum dose.

The Annual Meeting of the Obesity Society (Boston, Massachusetts, October 20-24)

The Obesity Society's annual meeting has long been our favorite place to catch up on the basic science research behind this critical problem. While the FDA has not approved a new obesity drug since 1999, we came away feeling optimistic that promising new treatments are on the horizon.

Society makes both weight loss and weight maintenance extremely difficult.

In our current "obesogenic" environment, junk food is invariably cheaper than healthy food and people must schedule time to exercise because physical activity is so absent from our daily routines. Poor neighborhoods often lack grocery stores or safe places to exercise. Even when people do lose weight, both biological mechanisms and the pull of environmental lures makes weight difficult to keep off.

Low efficacy and reimbursement hamper use of current obesity drugs.

Two prescription drugs are currently available for long-term weight management treatment: orlistat (Xenical) and sibutramine (Meridia). Both drugs cause about 5% loss of total body weight, which is enough to improve several medical measures of metabolic health but which, for many people, would not be very noticeable. In addition, the side effects can be quite unpleasant or downright worrisome: Xenical causes problems with oily stools and Meridia tends to raise blood pressure. Because obesity continues to be viewed as a lifestyle choice rather than as a medical condition, few insurers cover these drugs.

Bariatric surgery is effective but invasive and expensive.

Surprisingly, neither physical restriction of the stomach's size nor mal-absorption of nutrients is the main cause of weight loss when people get gastric bypass surgery. While both do play a role in short-term weight loss, the most important change that occurs in people who get gastric bypass surgery is in the way their small intestines secrete gut hormones (a.k.a. incretins) in response to food. In the short term, these hormonal changes can reverse obesity-associated type 2 diabetes, even before patients begin losing weight! In the long term, surgery patients will feel full more easily and eat less, allowing them to keep off the weight in the initial months after surgery.

The obesity pipeline is rich in neuroendocrine therapies.

Rimonabant, a drug that reduces weight that is currently under review by the FDA, acts on the central nervous system to decrease appetite. Rimonabant seems slightly more effective than Xenical and Meridia, but side effect concerns include depression and anxiety - if you are interested in taking any new medicine, of course, always ask your doctor or healthcare team about side effects. Further down the road, but perhaps more promising, is the possibility of using incretin therapeutics to treat obesity. As we discussed in our previous issue, both Byetta and Symlin are incretin hormones that cause weight loss when used for diabetes. Amylin, the maker of both drugs, is researching combinations of Symlin and another compound, leptin, as well as other hormones involved in appetite regulation. Results in rats have been promising, and although human immune systems are very different from those of rats, we look forward to seeing data on how these combinations work in humans.