Glucose levels in the normal range predict incident diabetes in families with premature coronary heart disease

Purpose: Little is known about excess risk of incident diabetes conferred by fasting plasma glucose (FPG) within the normal range (<5.6 mmol/l) for high risk families. Methods: Healthy 30-59 year old non-diabetic siblings (N = 542) of index cases with documented premature coronary disease were followed prospectively for type 2 diabetes. Results: During 8.7 ± 3 years of follow-up, incident diabetes was identified in 7.8%. Rates were incremental with baseline non-diabetes FPG thresholds of 5.0, 5.6, 6.1, and 6.7 mmol/l (p for trend <0.0001). FPG was the strongest predictor of incident diabetes even across levels within the normal range. The multivariable adjusted relative risk was 14.9 (95% CI = 3.4-65.2) at FPG thresholds ≥5.0 mmol/l versus FPG <5.0 mmol/l. The maximal diagnostic efficiency for FPG was 5.50 mmol/l; with sensitivity and specificity 0.782. All FPG thresholds in the normal range between 5.0 and 5.6 mmol/l showed efficiency levels >0.74. The overall area under the ROC curve predicting incident diabetes for normal and prediabetes ranges of FPG was 0.867. Conclusion: Higher FPG levels within the designated "normal" range in high risk families are a potent independent risk factor for type 2 diabetes and may serve as a sentinel to trigger primary preventive interventions.