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HbA1c Underestimates Plasma Glucose in People Taking Antiretrovirals
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48th ICAAC, October 25-28, 2008, Washington, DC
Mark Mascolini
Hemoglobin A1c (HbA1c) underestimated average plasma glucose by 29 mg/dL in a case-control comparison of 100 antiretroviral-treated people and 200 HIV-negative people [1]. Colleen Hadigan and colleagues at the National Institute of Allergy and Infectious Diseases (NIAID) found that abacavir use and increased mean corpuscular volume (MVC) associated with nucleoside (NRTI) therapy strongly predicted the discordance between HbA1c and glucose.
"Our study suggests that, for HIV-infected patients on NRTI-based antiretroviral therapy, especially those with macrocytosis or those on abacavir, the use of HbA1c may be inaccurate," the NIAID team concluded. "Fructosamine appears to be an appropriate alternative for the assessment of glycemia in this population of patients."
Hadigan and coworkers planned the study because earlier reports found that HbA1c underestimated fasting plasma glucose in people with HIV [2,3]. The authors of both earlier studies speculated that hemolysis played a part in the misleading HbA1c, but neither study fully characterized these unexpected findings.
The NIAID team devised a case-control study that matched 100 HIV-infected people with type 2 diabetes or hyperglycemia to 200 HIV-uninfected controls with type 2 diabetes. Controls were matched to cases by gender, race, and age within 2 years. Hadigan and colleagues used random serum glucose and HbA1c values from the 200 controls to create a linear regression reference equation describing the relationship between HbA1c and glucose.
The investigators defined diabetes as a documented diagnosis, at least 2 fasting plasma glucose measures at or above 126 mg/dL, or a casual plasma glucose at or above 200 mg/dL. Hyperglycemia meant a fasting plasma glucose at or above 100 mg/dL and under 126 mg/dL at least once in the past year. The analysis excluded people with hemoglobinopathy, changes in antiretroviral or glucose therapy within 3 months, a hemoglobin below 9 g/dL, an active or recent opportunistic infection, end-stage renal disease or creatinine above 1.8 mg/dL, blood transfusion within 3 months, use of corticosteroids within 3 months, or current or recent pregnancy. Case patients completed 2 visits, one after fasting for at least 6 hours and one nonfasting. The investigators collected random glucose measures from all 200 controls on the same day.
Mean age for cases and controls stood at 52 years, 70% were men, 65% African American, 25% white, and 7% Hispanic. The HIV group had been infected for an average 13.5 years and had an average CD4 count of 561. Sixty-one of the 100 HIV-infected people had a viral load below 50 copies.
Comparing cases and controls, Hadigan and coworkers determined that HbA1c underestimated mean plasma glucose by 29 +/- 4 mg/dL. Several factors correlated with HbA1c-glucose discordance (defined as measured minus predicted glucose):
· Use of NRTIs (P < 0.002)
· Use of abacavir (P = 0.001)
· Use of lamivudine (P = 0.02)
· Use of zidovudine (P = 0.03)
· Mean corpuscular volume (P = 0.0001)
· Hemoglobin (P = 0.04)
· Serum albumin (P = 0.03)
· Low HIV load (P = 0.02)
· Low haptoglobin (P = 0.01)
Age, duration of diabetes or HIV, insulin therapy, CD4 count, and current treatment with a protease inhibitor or nonnucleoside had no impact on HbA1c-glucose discordance.
Multivariate analysis considering all the significant factors isolated only abacavir use (P = 0.0004) and mean corpuscular volume (P = 0.001) as independent predictors of HbA1c-glucose discordance.
Fructosamine more closely reflected plasma glucose in HIV-infected people, with an average measured minus predicted plasma glucose of 2.8 (+/- 5.0) mg/dL. This small discordance was not associated with use of different antiretroviral classes or individual drugs, CD4 count, viral load, or hematologic measures.
The NIAID investigators called for further research to characterize the mechanism behind the HbA1c-glucose discordance in people with HIV.
References
1. Kim P, Woods, C, Crum D, et al. Hemoglobin A1c does not accurately reflect glycemia in patients on HAART. 48th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC). October 25-28, 2008. Washington, DC. Abstract H-2304.
2. Polgreen PM, Putz D, Stapleton JT. et al. Inaccurate glycosylated hemoglobin A1C measurements in human immunodeficiency virus-positive patients with diabetes mellitus. Clin Infect Dis. 2003;37:e53-e56.
3. Diop ME, Bastard JP, Meunier N, et al. Inappropriately low glycated hemoglobin values and hemolysis in HIV-infected patients. AIDS Res Hum Retroviruses. 2006;22:1242-1247.
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