Objective: Since glycohemoglobin values are widely used clinically as a surrogate for average glucose concentration over an extended period of time, we decided to determine the actual relationship between 24-hour integrated glucose values and percent total glycohemoglobin (%tGHb) in cohorts of people with and without diabetes. Research Design and Methods: In 48 people without known diabetes with known stability of fasting glucose over a 1-year period of time, the calculated 24-hour integrated glucose concentration was compared with their %tGHb. In 15 normal young medical students, the glucose area response was determined from 46 venous blood samples obtained during a 24-hour period and compared with their %tGHb. In 18 people with type 2 diabetes, interstitial glucose concentrations were monitored using the Continuous Glucose Monitoring System (Medtronic MiniMed, Inc., Sylmar, Calif) for 3 days at 20-day intervals over 100 days. %tGHb was performed at 20-day intervals simultaneously. In 29 people with untreated type 2 diabetes, glucose area response was determined from 46 venous blood samples obtained during a 24-hour period and compared with their %tGHb after being on a standardized diet provided to the subjects for at least 5 weeks. The %tGHb and 24-hour profiles were stable. Results: There was an excellent correlation between the mean 24-hour glucose concentration and the %tGHb among subjects with diabetes. The correlation was poor among subjects without diabetes. The relationship was curvilinear when plotted as a single group. Alternatively when data from subjects with or without diabetes were plotted separately, the slopes were identical but the y-intercepts were different. Conclusion: The relationship between the mean glucose concentration integrated over an extended period of time and the %tGHb is not linear. The reason for this nonlinearity remains to be determined. This non-linearity needs to be considered in the clinical interpretation of %tGHb (and probably HbA 1c) in reference to glucose values.