April 27 : A new study has identified ten genetic variants associated with type 2 diabetes. They are now hopeful that the discovery will lead to the development of new drugs for diabetes, permit more effective targeting of drug and behavioural therapies, and help scientists and physicians better predict who will develop diabetes.

Type 2 diabetes is characterized by high levels of blood sugar, caused by the body’s inability to utilize insulin to move blood sugar into the cells for energy.

The study was conducted by Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study group in collaboration with two other groups at the University of Michigan School of Public Health and was lead by Michael Boehnke.

As part of the study, researchers used a relatively new strategy known as a genome-wide association study, to scan the genomes of more than 2,300 Finnish by typing more than 300,000 strategically selected markers of genetic variation. About half of the participants had type 2 diabetes and the other half had normal blood glucose levels.

Researchers compared their initial findings with results from genome-wide studies of 3,000 Swedish and Finnish participants carried out by the Diabetes Genetics Initiative and 5,000 British participants done by the Wellcome Trust Case Control Consortium and UK Type 2 Diabetes Consortium to validate their findings.

After identifying promising leads through this approach, the three research teams jointly replicated their findings by testing more focused sets of genetic markers in additional groups totaling more than 22,000 people from Finland, Sweden, Poland, the United States and the United Kingdom.

Researchers found at least four new genetic factors associated with increased risk of diabetes and confirmed the existence of another six.

“Until recently we knew very little about the genetic architecture of type 2 diabetes. This is certainly not the complete genetic architecture for diabetes, but we have come a long way in better understanding the genetic basis for this disease,” Boehnke said.

The newly identified diabetes-associated variations lie in or near:

IGF2BP2 - This gene codes for a protein called insulin-like growth factor 2 mRNA binding protein 2. Insulin-like growth factor 2 is thought to play a role in regulating insulin action.

CDKAL1 - This gene codes for a protein called CDK5 regulatory subunit associated protein1-like1. The protein may affect the activity of the cyclin dependent kinase 5 (CDK5) protein, which stimulates insulin production and may influence other processes in the pancreas’s insulin-producing cells, known as beta cells. In addition, excessive activity of CDK5 in the pancreas may lead to the degeneration of beta cells.

CDKN2A and CDKN2B - The proteins produced by these two genes inhibit the activity of cyclin-dependent protein kinases, including one that has been shown to influence the growth of beta cells in mice. Interestingly, these genes have been heavily studied for their role in cancer, but their contribution to diabetes comes as a complete surprise.

Chromosome 11 - One intriguing association is located in a region of chromosome 11 not known to contain any genes. Researchers speculate that the variant sequences may regulate the activity of genes located elsewhere in the genome, but more work is needed to determine the exact relationships to pathways involved in type 2 diabetes.

The diabetes-associated genetic variants that were confidently confirmed by the new research are: TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11 and FTO.

“By identifying these genes, we are identifying potential loci for drug action and suggesting classes of compounds that might be useful to help develop drugs to treat diabetes,” Boehnke said.

The findings of the research appeared in the online edition of the journal Science. (ANI)