Biological Variation of Glycohemoglobin

Extract

Glycohemoglobin (GHb) is a measure of long-term mean glycemia that predicts risks for the development and/or progression of diabetic complications in patients with type 1 and type 2 diabetes (1)(2). Several reports have suggested, however, that although the within-subject variation in GHb unrelated to glycemia is minimal, there is substantial between-subject variation in GHb, e.g., “low glycators” and “high glycators” (3)(4)(5). These reports have suggested that because of this large between-subject variation, GHb may not be useful for diabetes screening or diagnosis and that when GHb is used for routine management of patients with diabetes, different patients may require very different GHb target values to achieve the same overall glycemic status. We therefore examined the biological variation of GHb and fasting plasma glucose (FPG) in nondiabetic individuals.

Individuals without diabetes (n = 48) participated in a study of an artificial sweetener that has no effect on GHb or plasma glucose concentrations [Submission to Food and Drug Administration. McNeil Specialty Products Company food additive petition 7A3987 (Sucralose), 1987–1997]. Because the study was designed to detect minimal changes in plasma glucose concentrations, all participants were men to avoid the effects of cyclic hormonal changes on insulin (and therefore, plasma glucose) concentrations. At the prestudy screening, all individuals were healthy on the basis of a medical history, physical examination, and electrocardiography results; results of hematology and blood chemistry studies, urine examination, and measures of blood glucose control (FPG, insulin, C-peptide, and hemoglobin A_1c) were all within their respective reference intervals. Participants who failed a baseline oral glucose tolerance test [fasting >7.8 mmol/L (140 mg/dL), 1 h >11.1 mmol/L (200 mg/dL), and/or 2 h >7.8 mmol/L (140 mg/dL)] were excluded. Those who took medications that could affect glucose metabolism or who failed a drugs-of-abuse screen, had a history of a gastrointestinal disorder, or had a history of consuming more than two alcoholic drinks per day were also excluded. Serial samples for FPG and GHb analysis were collected by venipuncture after a minimum 8-h overnight fast on a weekly basis for a total of 12 visits. Three men with <10 data points for either FPG or GHb were excluded from the analysis. The study received approval from the institutional review boards of all participating study centers, and all individuals gave informed consent before their participation.