A genotype score of nine validated SNPs that are associated with modulation in levels of LDL or HDL cholesterol was an independent risk factor for incident cardiovascular disease. The score did not improve risk discrimination but did modestly improve clinical risk reclassification for individual subjects beyond standard clinical factors.

Identification of individuals at high risk of developing type 2 diabetes is a prerequisite for prevention of the disease. We therefore studied risk factors predicting type 2 diabetes in the Botnia Study in western Finland. A total of 2,115 nondiabetic individuals were prospectively followed with repeated oral glucose tolerance tests. After a median follow-up of 6 years, 127 (6%) subjects developed diabetes. A family history of diabetes (hazard ratio [HR] 2.2, P ‫؍‬ 0.008), BMI (HR for comparison of values below or above the median 2.1, P < 0.001), waist-to-height index (2.3, P < 0.001), insulin resistance (2.1, P ‫؍‬ 0.0004), and ␤-cell function adjusted for insulin resistance (2.7, P < 0.0001) predicted diabetes. Marked deterioration in ␤-cell function with modest changes in insulin sensitivity was observed during the transition to diabetes. The combination of FPG >5.6 mmol/l, BMI >30 kg/m 2 , and family history of diabetes was a strong predictor of diabetes (3.7, P < 0.0001). Of note, using FPG >6.1 mmol/l or 2-h glucose >7.8 mmol/l did not significantly improve prediction of type 2 diabetes. In conclusion, a marked deterioration in ␤-cell function precedes the onset of type 2 diabetes. These individuals can be identified early by knowledge of FPG, BMI, and family history of diabetes. Diabetes 54: 166 -174, 2005

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