Findings are consistent with the fact that A1c is a more specific test in diagnosing prediabetes and diabetes compared to fasting plasma and 2-hour post challenge glucose tests. Increased specificity of A1c implies a more advanced state of prediabetes at diagnosis.
It is not surprising then to see that rates of cardiovascular disease and all-cause mortality are higher in prediabetics identified by A1c rather than fasting or post stress glucose levels.
We compared the risk of cardiovascular disease (CVD) and all-cause mortality in subgroups of prediabetes defined by fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), or HbA1c.
RESEARCH DESIGN AND METHODS
In the Whitehall II cohort, 5,427 participants aged 50–79 years, without diabetes, were followed for a median of 11.5 years. A total of 628 (11.6%) had prediabetes by the World Health Organization (WHO)/International Expert Committee (IEC) criteria (FPG 6.1–6.9 mmol/L and/or HbA1c 6.0–6.4%), and 1,996 (36.8%) by the American Diabetes Association (ADA) criteria (FPG 5.6–6.9 mmol/L and/or HbA1c 5.7–6.4%). In a subset of 4,730 individuals with additional measures of 2hPG, 663 (14.0%) had prediabetes by 2hPG.
Incidence rates of a major event (nonfatal/fatal CVD or all-cause mortality) were compared for different definitions of prediabetes, with adjustment for relevant confounders.
Compared with that for normoglycemia, incidence rate in the context of prediabetes was 54% higher with the WHO/IEC definition and 37% higher with the ADA definition (P < 0.001) but declining to 17% and 12% after confounder adjustment (P ≥ 0.111).
Prediabetes by HbA1c was associated with a doubling in incidence rate for both the IEC and ADA criteria. However, upon adjustment, excess risk was reduced to 13% and 17% (P ≥ 0.055), respectively. Prediabetes by FPG or 2hPG was not associated with an excess risk in the adjusted analysis.
Prediabetes defined by HbA1c was associated with a worse prognosis than prediabetes defined by FPG or 2hPG. However, the excess risk among individuals with prediabetes is mainly explained by the clustering of other cardiometabolic risk factors associated with hyperglycemia.