Can genetic risks accurately predict Type 2 diabetes?

Clinical Risk Factors, DNA Variants, and the Development of Type 2 Diabetes
Original source: New England Journal of Medicine Volume 359, Number 21
Authors: Valeriya Lyssenko, Anna Jonsson, Peter Almgren, Nicoló Pulizzi, Bo Isomaa, Tiinamaija Tuomi, Göran Berglund, David Altshuler, Peter Nilsson, and Leif Groop
Publication date: November 20, 2008
DOI (digital document ID): not available
Requires subscription? Yes
Publicly-available abstract: Yes

Synopsis:
The aim of this paper is to determine whether environmental and clinical risk indicators, genetic factors, or both can be used to predict whether or not a person will develop Type 2 diabetes.

The authors singled out 16 specific gene markers that might be used to predict risk or development of diabetes. They tracked those, plus known environmental and clinical risk indicators, for over 16,000 Swedish patients and over 2500 Finnish patients, for a median period of 23.5 years. They studied the effect of variations of the gene markers on insulin secretion and insulin action over this period of time.

Over the observation period, approximately 11.7% of the subjects developed diabetes. Variations in 11 of the genes studied were associated with developing diabetes, independent of other risk indicators. Variants in eight of those genes were specifically associated with impaired beta cell function.

Adding the genetic risk to the clinical and environmental indicators slightly improved the long-term ability to predict whether or not an individual would develop Type 2 diabetes. This predictive ability increased with the duration of the follow-up.

Reliability:
While a large population was observed, and the medium observation time was over 20 years, the abstract does not provide insight into the distribution of follow-up duration, to let us know whether the median is a statistically-significant number. The improved prediction ability turns out to be about 1.5% better than the accuracy without the genetic information, which may not be cost-effective at the present time.

Practical Applications:
Known genetic risk is sometimes an incentive for making lifestyle changes to reduce the other risks for developing diabetes.

If the full paper shows direct correlations between insulin secretion, insulin resistance, and genetic variations, then initial pharmaceutical therapy can be better targeted to the individual's needs.

This synopsis was based on the abstract only.

Where do beta cells come from? A new method of studying human islet cell development

Beta Cells within Single Human Islets Originate from Multiple Progenitors
Original source: PLoS ONE 3(10): e3559
Authors: Raphaël Scharfmann, Xiangwei Xiao, Harry Heimberg, Jacques Mallet, Philippe Ravassard (corresponding author)
Publication date: October 29, 2008
DOI (digital document ID): 10.1371/journal.pone.0003559
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
Beta cells are the insulin-producing cells within the Islets of Langerhans, located in the pancreas. Most of our understanding of how beta cells develop is based on studies of mice and rats. The authors' goal was to develop a model to transfer genes into developing human pancreas cells and to see if the gene transfer worked by looking at how the cells multiplied and specialized.

Pancreas cells were removed from human fetuses and tagged with a specific virus tag, called a replication-defective lentivirus, and islet-cell specific DNA from human pancreas tissue. These tissues were were grafted onto mice whose were treated to not reject the transplant. This technique had previously been tested to make sure it would be able to grow new human cells from the grafted cell, and that the tags would only show up on new cells grown from the grafted tissue. The tagged cells were allowed to grow and differentiate, to create new islet bodies. The new human islets contained both tagged and untagged cells, suggesting that islet cell growth is more than a simple matter of cell multiplication.

Reliability:
The authors are professionals in the fields of medicine, medical research, and diabetes research, and associated with accredited institutions. The research was published in a peer-reviewed journal. The article explained the technical details of tissue preparation and growth. The research was funded, but not directed, by grants from a combination of diabetes-research foundations.

Practical Applications:
This investigation falls under the heading of primary research -- how islet cells form and develop -- which is considered one of the key issues involved in understanding and curing diabetes.

Ethics note:
Studies using human cells -- such as the fetus cells and human pancreas cells used in this experiment -- must meet certain ethical standards. In this case, the fetuses came from pregnancies the parents chose to abort between the 9th and 11th weeks of pregnancy, and the cells were taken with the informed consent of the mothers. The human pancreas cells were taken from a pancreas that had been lawfully donated for transplantation and research.

This synopsis was based on the entire article.