Novel biomarkers and genetic variants for type 2 diabetes in Latinos

The shape of glucose response and one hour (1-hr) glucose during an oral glucose tolerance test (OGTT) are emerging biomarkers for type 2 diabetes. The purpose of this study was two-fold: (1) to investigate the utility of these novel biomakers to differentiate type 2 diabetes risk in Latino youth, and (2) to examine the genetic determinants in a Latino population.

Data from the ASU Arizona Insulin Registry (AIR) registry and the USC Study of Latino Adolescents at Risk for diabetes project were used to test the cross-sectional and prospective utility of novel biomarkers to identify youth at risk for type 2 diabetes. Pediatric and adult data from the ASU AIR registry were assessed to examine the association of single nucleotide polymorphisms (SNPs) with type 2 diabetes risk. Three KCNQ1 SNPs (rs151290; rs2237892; rs2237895) were examined as novel genetic variants for type 2 diabetes in Latinos.

Latino youth with a biphasic response in the AIR registry exhibited significantly better β-cell function (P < 0.05) compared to youth with a monophasic response. Additionally, Latino youth with a 1-hr glucose ≥155 mg/dL exhibited a significantly greater decline in β-cell function over 8 years compared with the <155 mg/dL group (β=-327.8±126.2, P = 0.01). Moreover, a 1-hr glucose ≥155 mg/dL was associated with a 2.5 times greater risk for developing prediabetes over time (P = 0.0001). 1-hr glucose was the most powerful predictor of prediabetes (area under the receiver operating characteristic curve=0.73) when compared to the traditional biomarkers including HbA1c (0.58), fasting (0.67), and 2-hr glucose (0.64). Two KCNQ1 SNPs (rs151290 and rs2237892) exhibited significant associations with type 2 diabetes risk factors. For the novel glycemic markers, 15 SNPs were associated with the glucose response curve, while 18 SNPs were associated with 1-hr glucose.

These data suggest that glucose response curve and 1-hr glucose during an OGTT independently differentiate type 2 diabetes risk among Latino youth. Furthermore, it was successful to replicate the association of type 2 diabetes risk with 2 KCNQ1 SNPs in a Latino population. Data suggest that novel glycemic biomarkers are influenced by genetic background in this high-risk population.