Scientists have discovered three unsuspected regions of human DNA that contain clear genetic risk factors for type 2 diabetes, and another that is associated with elevated blood triglycerides.
The findings stem from the work of the Diabetes Genetics Initiative (DGI), a public-private partnership between the Broad Institute of MIT and Harvard, Novartis and Lund University, and they also reflect a close partnership with two other di?betes research groups.
The three groups’ studies, which appeared together in a recent advance online edition of Science, are among the first to apply a suite of genomic resources to clinical research. These genomic resources include the Human Genome Project, the SNP and HapMap Projects, and genome-scale laboratory and analytical tools.
“For the first time, it is possible to look across the human genome and discover new clues about the root causes of common, devastating diseases that arise from a combination of genes, environment and behavior,” said senior author David Altshuler, a principal investigator of DGI, director of the Broad Institute’s program in medical and population genetics and a professor at Massachusetts General Hospital and Harvard Medical School.
“The confirmed genetic contributors we and our collaborators have found open surprising new avenues for disease research, treatment and prevention,” he said.
With the aging of the population and the frequent excesses of modern lifestyles, type 2 diabetes and cardiac risk factors constitute a looming threat to human health, particularly in industrialized nations. Solutions to this burgeoning problem must include new, more effective treatments and the ability to identify “at risk” individuals–each of which requires innovative directions for future research.
The DGI study is one of the first large-scale studies of human genetic variability, aiming to reveal genetic connections to type 2 diabetes and other cardiovascular risk factors such as blood insulin levels, cholesterol levels, blood pressure and body weight. Each of these traits is considered “complex” because it involves a mix of inherited, environmental and behavioral factors.
The scientists’ approach, known as a “genome-wide association study,” involves scanning thousands of individuals’ genomes for single letter changes, called single nucleotide polymorphisms (SNPs). Due to the block-like nature of the human genome, certain SNPs can serve as signposts, highlighting pieces of nearby DNA that may play a causal role in disease.
Using this approach, the DGI team and their collaborators identified and confirmed three novel regions of the genome that influence the risk of type 2 diabetes, as well as a genomic region that is linked with blood triglyceride levels. Perhaps the most intriguing result involves a DNA region that lies far from any known annotated genes. Such genomic “outsiders” would have been incredibly difficult to find by traditional hypothesis-driven approaches.
The other regions linked to diabetes lie near genes with known biochemical functions, but ones never before connected to the disease. Interestingly, the region implicated in triglyceride levels involves a gene that has long been known to play a role in modulating blood glucose.
Based on initial results, the DGI scientists turned to replicating the most promising findings in independent samples–a critical aspect of the genomic method. The scientists worked together with two other groups that performed similar genomic analyses of type 2 diabetes: the Wellcome Trust Case Control Consortium/UK Type 2 Diabetes Genetics Consortium (WTCCC/UKT2D) and the Finland-United States Investigation of NIDDM (non-insulin-dependent diabetes mellitus) Genetics (FUSION).
By virtue of their close collaboration, DGI, WTCCC/UKT2D and FUSION researchers identified at least eight clear genetic risk factors for type 2 diabetes, including three that had never before been found, as well as several other probable risk factors that warrant further study.
Source: MIT
–
A diet rich in fiber from cereals and in magnesium may help lower the risk of developing type 2 diabetes, German researchers report.
Ann Albright, president-elect for health care and education at the American Diabetes Association, said the suggestion that fiber from cereal might be better than fiber from fruits and vegetables in preventing type 2 diabetes “warrants further investigation. But I don’t think we should take away the idea that fruits and vegetables are not important,” she added.
As for the nutrient magnesium, “there are a whole lot of challenges around the study of micronutrients,” Albright said. “They are difficult to study. I don’t think the public health message is that we should go out and up our intake of magnesium.”
The mechanism by which magnesium intake might affect the risk of diabetes “is unclear,” she said.
Type 2 diabetes, which generally occurs in the adult years as the body loses it ability to metabolize sugar adequately, is a growing problem, due largely to growing obesity rates, the German researchers noted. Estimates suggest that the ?umber of people worldwide with type 2 diabetes may rise from 171 million in 2000 to 370 million by 2030, according to background information in the article. The associated illnesses, death and health-care costs linked to the disease underscore the need for effective preventive measures, the study authors noted.
For the study, conducted by researchers at the German Institute of Human Nutrition Potsdam-Rehbruecke, more than 9,700 men and 15,365 women, 35 to 65 years old, who completed a food questionnaire were then followed for an average of seven years.
The researchers also did a meta-analysis — or review — of previous studies about the relationship between fiber or magnesium intake and risk of diabetes.
Dividing people in the study into five groups based on their intake of fiber from cereals, the researchers found that those who ate the most had a 27 percent lower risk of developing type 2 diabetes than those who ate the least. Greater fiber intake from fruits and vegetables was not associated with diabetes risk, the study found.
Participants who consumed the most magnesium had a 23 percent lower risk of developing type 2 diabetes than those who consumed the least. Green vegetables such as spinach are good sources of magnesium, as are nuts like almonds and cashews.
The research did not touch directly on one important lifestyle issue, physical activity, Albright said. Many other studies have shown “strong evidence of physical activity, as it relates to weight loss, in preventing or delaying development of diabetes,” she said.
“So, the take-home messages are that people do need to keep their weight in a healthy range,” she said. “And fiber intake is a major component of a healthy diet.”
The source of the fiber — fruits, vegetables or cereals — does not seem to be of major importance, Albright said. “Unfortunately, many people do not get a lot of fiber in their diet,” she said.
And many people do not get enough physical activity — 30 minutes a day, most days of the week, is recommended, Albright said.
The findings were published in the May 14 issue of Archives of Internal Medicine.