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Severely short Ecuadorians resistant to diabetes, cancer, study says

By Madison Park, CNN
Dr. Jaime Guevara-Aguirre has examined the health outcomes of Ecuadorian patients affected by dwarfism for 22 years.
Dr. Jaime Guevara-Aguirre has examined the health outcomes of Ecuadorian patients affected by dwarfism for 22 years.
STORY HIGHLIGHTS
  • Study: Cancer, diabetes don't seem to affect Ecuadorians with a specific form of dwarfism
  • The lack of growth hormone receptors could have protective effect on cells
  • In 22-year study, life expectancies didn't rise because patients died from other causes

(CNN) -- For years, Dr. Jaime Guevara-Aguirre of Quito, Ecuador, noticed that his shortest patients never seemed to get the common ailments that befell others.

These patients had a genetic mutation that would not allow them to grow more than 4 feet tall -- their heights would be fixed to that of a 7-year-old for life.

Although they aged, Guevara-Aguirre noticed that "they developed neither cancer nor diabetes." "That was fascinating," he said.

That observation launched a 22-year study.

The study published Wednesday in Science Translational Medicine monitored a group of 99 Ecuadorians -- described as being of "severe short stature." The mechanisms that stunt their growth could potentially prevent cancer and diabetes, according to the findings.

Guevara-Aguirre and the co-authors compared the living participants' health with that of their close relatives who were of regular height. Those blood relatives "developed diabetes like the general Ecuadorian population, about 20% of them have died of cancer," Guevara-Aguirre said.

Yet of all the severely short patients only one got cancer in the 22-year period. After receiving treatment for ovarian cancer in 2008, she has remained cancer-free.

Researchers also looked at detailed death information on 53 severely short people who were not part of the study. They found no evidence of cancer or diabetes-related deaths there.

Despite this resistance to diabetes or cancer, life expectancy of the study subjects didn't rise.

Tips for managing diabetes

"The answer is, it doesn't lead to life extension," said Dr. Valter Longo, one of the authors in the study. "It leads to major reduction in cancer and diabetes."

During the course of the study, nine of the 99 participants with dwarfism died. Their common killers were age-related diseases such as heart disease and stroke. Compared with their relatives of regular height, they "died much more frequently from accidents, alcohol-related causes, and convulsive disorders," according to the study.

"They do have potential to live longer if they don't die of weird causes of death-accidents, alcohol-related conditions," said Longo, an associate professor of biological sciences at the University of Southern California.

Dwarfism can be caused by several factors, including genetics, kidney disease or hormones.

The severely short Ecuadorians in the study have a specific mutation in their growth hormone receptor gene.

Although their pituitary glands produce enough growth hormones, their receptors are missing. That inability to bind to receptors means another growth hormone, called insulin-like growth factor-1 is not well-produced. This condition is known as Laron syndrome.

The affected Ecuadorians are descendants of Spanish Jews who escaped to South America to avoid the Inquisition and converted to Christianity, according to the researchers. The mutation is prevalent in this gene pool.

The findings from this study raise questions about the relationship between growth hormones and diseases.

"We treat adults who become growth hormone deficient with growth hormones. Studies like this, makes us pause," said Dr. Roberto Salvatori, associate professor of medicine in the division of endocrinology and metabolism at Johns Hopkins University School of Medicine.

In more than two decades with nearly 100 patients affected by dwarfism, Guevara-Aguirre has had one cancer case.
In more than two decades with nearly 100 patients affected by dwarfism, Guevara-Aguirre has had one cancer case.

In the West, growth hormones have been used illegally as anti-aging treatments. Growth hormone treatments have been known to improve skin, wrinkles, water muscle retention and help with fat burning, Salvatori said.

"There are positive effects these can do, but you've got to wonder whether these people using growth hormones as anti-aging are going to have higher risk of diabetes or tumors," said Salvatori, who is not associated with the Ecuadorian study.

He cautioned that the subgroups in the study are extreme cases and may not apply broadly across all humans.

"It's hard to extrapolate," Salvatori said. The people in the Ecuador study have never had growth hormones since birth. "There are degrees of growth hormone deficiency. It's very extreme in genetic models," he said.

Salvatori conducted similar research on 65 Brazilians with a different form of dwarfism published in the Journal of Clinical Endocrinology & Metabolism in 2010. That study only recorded one death from cancer.

He said the findings in the Ecuadorian study are "very striking that there was no diabetes and cancer. This was our experience with the Brazilian dwarfs."

Laboratory models have shown similar findings in yeast, cells and mice. The deficiency of the growth hormones appeared to have some protective effects.

The mice that lacked growth hormone receptors lived 40 percent longer than other mice and were resistant to diabetes and cancer.

In human models, compared with the serum of their relatives, the samples from the severely short Ecuadorians had less DNA breaks. Their serum "can protect against oxidative DNA damage," according to the researchers.

As a possible explanation, "the cells don't grow as large or divide, but invest energy into the protective mechanism," Longo said.

Another paradox that puzzled researchers was that many of the Ecuadorians with dwarfism had poor diets and about 20 percent of them were obese.

"You have a population with increased obesity, yet no diabetes whatsoever," Longo said.

When their fasting glucose was measured, they had about a third of the amount as their relatives did and were more insulin-sensitive than their relatives.

RELATED TOPICS
  • Cancer
  • Diabetes
  • Ecuador
  • Genetics
  • Endocrinology

A life without diabetes and cancer isn't exactly easier, however.

Many living in urban areas face discrimination because of their height, Guevara-Aguirre said.

The participants deserve a lot of credit, he said, for their selfless contribution to science.

"The most important thing of this moment is that people in the world know that these patients have been cooperating for 22 years. They are helping to understand cancer and diabetes with their effort, blood, serum and cells."

 
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