Version July 2025
COMMENT —
The glycated hemoglobin (A1C) test is the test of choice for the assessment of overall glycemic management in patients with diabetes mellitus. A1C is one of a group of glycohemoglobins, stable minor hemoglobin components that are formed slowly and nonenzymatically from hemoglobin and glucose. The rate of formation of glycohemoglobins is proportional to the circulating glucose concentration integrated over the time of exposure. The level of A1C in a blood sample ordinarily provides a reliable measure of the glucose levels during the previous two to three months, reflecting the average 120-day life span of the erythrocyte and the normal turnover of the erythrocyte cell mass. Interpretation of the A1C level is valid only if the erythrocytes are produced and removed at the normal rate and are those of the patient. Sources of error include accelerated loss of the patient's red cell mass, in gastrointestinal bleeding as an example, and transfusion of blood from blood donors without diabetes, both of which can reduce the measured A1C level, as in the patient described above. A1C levels should not be ordered or interpreted under these circumstances [1].
The dangers of interpreting an A1C level in such a setting are undertreatment or mistreatment of diabetes. In the patient under consideration, reduction of insulin doses resulted in deterioration of glycemia and the need to readjust the insulin regimen thereafter. Treatment errors are more likely to occur in patients with complex, multisystem disease such as the one under consideration, in whom the clinician's attention to the nuances of diabetes management may be reduced by the need to address multiple issues under the pressure of time.
Glyburide is associated with a high risk of severe hypoglycemia in patients with impaired kidney function, as an example, when the creatinine clearance is <50 mL/min or the serum creatinine is >1.5 mg/dL in men or >1.4 mg/dL in women. The principal mode of removal of glyburide is hepatic clearance. However, glyburide is transformed in the liver to several derivatives, at least one of which has hypoglycemic activity and is removed by the kidneys. In patients with kidney impairment, the active derivative accumulates and causes hypoglycemia. Patients with glyburide-induced hypoglycemia should be admitted to the hospital until hyperglycemia returns, indicating the removal of the biologically active derivative.
Glyburide is not recommended for the treatment of type 2 diabetes in patients with chronic kidney disease [2]. If one wishes to prescribe a sulfonylurea in this setting, glipizide is a reasonable choice. It is used in approximately the same doses as glyburide, is not transformed into a derivative with hypoglycemic activity, and is inexpensive.
Metformin is contraindicated in the presence of chronic kidney disease, in patients with heart failure, and in patients otherwise at risk for acidosis because these conditions predispose the patient to lactic acidosis. When these contraindications are absent, the incidence of this life-threatening and often fatal disorder is extremely low.
[1,3]
