Genetic screening no better than traditional risk factors in predicting type 2 diabetes

Screening for a panel of gene variants associated with the risk for type 2 diabetes can identify adults at risk for the disease but is not significantly better than assessment based on traditional risk factors, such as weight, blood pressure and blood glucose levels.

Researchers analyzed data from 2,377 participants in the Framingham Offspring Study, which follows a group of adults who are children of participants in the original Framingham Heart Study. The researchers genotyped single nucleotide polymorphisms at 18 loci associated with diabetes to create a genotype score based on the number of risk-associated gene copies inherited. Then, the researchers compared the predictive value of genotype score to that of family history alone or of physiological risk factors.

During 28 years of follow-up, 255 of the 2,377 genotyped participants developed diabetes. Participants who developed diabetes had a mean genotype score of 17.7 compared with 17.1 among participants who did not develop diabetes (P<.001).

While the genotype score confirmed that inheriting more risk-associated alleles increased type 2 diabetes risk, the ability of the genotype score to discriminate those who did not develop diabetes from those who did was not significantly better than family history or individual risk factors, according to the researchers.

Diabetes was associated with a sex-adjusted OR of 1.12 per risk allele (95% CI, 1.07-1.17); the C statistic was 0.534 without the genotype score and 0.581 with the score (P=.01). Analysis of a model that adjusted for sex and self-reported family history of diabetes revealed a C statistic of 0.595 without the genotype score and 0.615 with the score (P=.11). Another model that adjusted for age, sex, family history, BMI, fasting plasma glucose, systolic blood pressure, HDL and triglycerides revealed a C statistic of 0.900 without the genotype score and 0.901 with the score (P=.49).

Use of the genotype score resulted in appropriate risk reclassification of 4% of participants. The value of screening may improve as more risk genes are identified, the researchers wrote.

“Although we did confirm that the more risk-associated gene variants you inherit the greater your risk for developing type 2 diabetes, genetic risk prediction for diabetes is still in its infancy,” James Meigs, MD, MPH, assistant physician in the General Medicine Division, Clinical Epidemiology Unit and Diabetes Research Unit at Massachusetts General Hospital, said in a press release. – by Katie Kalvaitis

N Engl J Med. 2008;359:2208-2219.

This study confirms the assertions that I put forward in a recent editorial for Endocrine Today (in production). Even with a combined analysis of 18 known diabetes risk alleles, the predictive value of this genotyping cannot exceed that of known clinical risk factors.

– Dawn Belt Davis, MD, PhD

Endocrine Today Editorial Board member