Inappropriately Low Glycated Hemoglobin Values and Hemolysis in HIV-Infected Patients

Abstract

In order to test the accuracy of glycated hemoglobin (HbA1c) in predicting mean glycemia in HIV-infected patients, we recorded consecutive HbA1c measurements from 1238 non-HIV-infected and 112 HIV-infected patients, all devoid of any hemoglobinopathy, in a retrospective, transversal study. Mean fasting glycemia from the six previous weeks (measured-Gly) and HbA1c-estimated glycemia [HbA1c-Gly (1.85x%HbA1c-4.78) mM] were compared. Mean hemoglobin, red cell volume, serum creatinine, CD4 count, and HIV viral load from the same period were collected in HIV-infected patients. Although measured-Gly was not significantly different between non-HIV-infected (6.95+/-3.23 mM) and HIV-infected patients (6.62+/-2.42 mM), HbA1c underestimated the mean fasting glycemia by 12.3% in HIV-infected as compared to non-HIV-infected patients (p=0.0001). The difference "measured-Gly-HbA1c-Gly" was correlated with the red cell volume (p<0.0001) in HIV-infected patients. We then searched for the presence of subclinical hemolysis, a cause of both macrocytosis and reduced HbA1c levels, in HIV-infected patients. To this end, we prospectively measured serum haptoglobin in 249 consecutive samples from HIV-infected subjects without any known cause of hemolysis. A very low haptoglobin level, a marker of hemolysis, was frequent and negatively correlated with the red cell volume in these patients. Treatment with nucleoside analogues was significantly associated with macrocytosis and low haptoglobin. In conclusion, HbA1c could be inappropriately low in HIV-infected patients. Its underestimation of mean fasting glycemia could be due to an antiretroviral-induced subclinical hemolysis, but further studies are needed to explore this hypothesis. Self-monitoring of blood glucose and search for latent hemolysis should be promoted in diabetic HIV-infected patients.

Advanced Glycation End Products Inhibit Both Infection and TransmissionIn Transof HIV-1 from Monocyte-Derived Dendritic Cells to Autologous T Cells

“…The potential consequences of these results must be analyzed with respect to the high incidence of diabetes and/or insulin resistance in the HIV-infected population (44,45). Furthermore, several studies have already shown the accumulation of circulating AGEs in HIV-infected patients, with or without metabolic syndromes (17)(18)(19). Circulating AGEs likely interact with their receptor RAGE in lymphocytes, monocytes/ macrophages, and DCs that are also targets and/or reservoirs of HIV-1.…”

“…Whatever the mechanism(s) involved, these perturbations result in the formation and accumulation both in blood and tissues of advanced glycation end product (AGE) molecules (10,11), a group of heterogeneous complex molecules produced by the nonenzymatic glycation between aldoses and free amino groups on proteins (12), DNA (13), or lipids (14). Elevated levels of circulating AGEs have been detected in patients with type 1 (15) and type 2 (16) diabetes, including patients infected with HIV-1 (17,18). Notably, AGEs have also been detected in patients with AIDS even in the absence of carbohydrate metabolism alteration (19).…”

A New Zealand Linkage Study Examining the Associations Between A1C Concentration and Mortality

“…To our knowledge, this finding has not been reported previously and warrants further investigation. However, it should be regarded as very preliminary, since it may be due to chance and because it is difficult to determine in a study of this type whether any increased risk of mortality in those with very low A1C levels is causal or merely a result of reverse causation due to preexisting disease (23).…”

How Sweet It Is? Susceptibility to Diabetes Mellitus in HIV-1 Treatment

“…Several recent studies have highlighted a possible discordance between Hb A1c and glucose levels in treated HIV infection, suggesting Hb A1c may under-represent overall glycemia [60,61]. Evidence of low-grade hemolysis (higher mean corpuscular volume and serum haptoglobin) in HIV-infected patients with diabetes mellitus was found to predict those patients whose Hb A1c was lower than expected for glucose levels [60]. Nucleoside analogs in particular were associated with low-grade hemolysis [60].…”

“…Evidence of low-grade hemolysis (higher mean corpuscular volume and serum haptoglobin) in HIV-infected patients with diabetes mellitus was found to predict those patients whose Hb A1c was lower than expected for glucose levels [60]. Nucleoside analogs in particular were associated with low-grade hemolysis [60]. These emerging data suggest caution in interpreting Hb A1c in treated HIV infection, particularly in patients receiving nucleoside analogs, when use of fructosamine may be indicated.…”