Relationship between fasting plasma glucose and glycosylated hemoglobin - Potential for false-positive diagnoses of type 2 diabetes using new diagnostic criteria

Context New criteria for the diagnosis of type 2 diabetes mellitus have rec ently been introduced that lowered the diagnostic fasting plasma glucose (F PC) concentration from 7.8 to 7.0 mmol/L (140 to 126 mg/dL). Objective To determine if individuals with diabetes diagnosed by the new FP C concentration criterion would have excessive glycosylation (elevated hemo globin [HbA(1c)] levels). Definitions We determined the distribution of HbA(1c) levels in individuals using 4 classifications: (1) normal by the new criterion (FPG concentratio n <6.1 mmol/L [110 mg/dL]; (2) impaired fasting glucose by the new criterio n (FPG concentration of 6.1-6.9 mmol/L [110-125 mg/dL]); (3) diabetes diagn osed solely by the new FPG concentration criterion of 7.0 through 7.7 mmol/ L (126-139 mg/dL); and (4) diabetes diagnosed. by the previous FPG concentr ation criterion of 7.8 mmol/L (140 mg/dL) or higher. Design Cross-sectional analysis of 2 large data sets (NHANES III and Meta-A nalysis Research Group [MRG] on the Diagnosis of Diabetes Using Glycated He moglobin) that contained individuals in whom FPG concentrations, 2-hour glu cose concentrations using an oral glucose tolerance test, and an HbA(1c) le vel were simultaneously measured. We cross-tabulated FPG concentrations (<6 .1 mmol/L [110 mg/dL], 6.1-6.9 mmol/L [110-125 mg/dL],7.0-7.7 mmol/L [126-1 39 mg/dl],and greater than or equal to 7.8 mmol/L [140 mg/dl]) and HbA(1c) levels separated into 3 intervals: normal, less than the upper limit of nor mal (ULN); slightly elevated, ULN to ULN plus 1%; and high, higher than ULN plus 1%. Results Among subjects with normal FPC concentrations, HbA(1c) levels in th e NHANES I II land the MRC) data sets were normal in 97.3% (96.2%), slightl y elevated in 2.7% (3.6%), and high in 0.1% (0.2%). Among individuals with impaired fasting glucose, HbA(1c) concentrations were normal in 86.7% (81.4 %), slightly elevated in 13.1% (16.4%), and high in 0.2% (2.2%). Among diab etic patients diagnosed by the new FPC criterion only, HbA(1c) levels were normal in 60.9% (59.6%), slightly elevated in 35.8% (32.8%), and high in 3. 4% (7.6%). In diabetic patients diagnosed by the former FPG criterion, HbA( 1c) levels were normal in 18.6% (16.7%), slightly elevated in 32.5% (21.0%) , and high in 48.9% (62.3%). Conclusions About 60% of the new cohort of diabetic patients in both data s ets have normal HbA(1c) levels. We believe that diabetes should not be diag nosed in those with FPC concentrations less than 7.8 mmol/L (140 mg/dL) unl ess excessive glycosylation is evident. Individuals without excessive glyco sylation but with moderate elevations of FPG concentrations (6.1-7.7 mmol/L [110-139 mg/dl]) should be diagnosed as having impaired fasting glucose an d treated with an appropriate diet and exercise. This diagnostic labeling a chieves the goal of early intervention without subjecting these persons to the potentially negative insurance, employment, social, and psychological c onsequences of a diagnosis of diabetes mellitus.