The hormone insulin helps cells absorb sugar from the blood. In cases of pre-diabetes, cells gradually lose their ability to respond to the effects of insulin. As a result, blood sugar levels can remain high for prolonged periods of time. The pancreas gland, which produces insulin, is forced to make ever-high amounts of this hormone to try to stimulate cells to reduce blood sugar. If this continues over a period of years, the pancreas gets exhausted and can eventually fail.
Keeping track of blood sugar levels is an important part of health monitoring for HIV positive people. In addition to specifically checking fasting blood sugar levels, a test called hemoglobin A one c, written as HbA1c, is usually done at regular intervals, as it can give doctors a rough average of what blood sugar levels were like over the past three months. Results from HbA1c tests appear as a percentage. The normal range for HbA1c is 7% or less. Every 1% rise in HbA1c tests suggests that average blood sugar levels have risen by about 2 mmol/litre.
HbA1c and HIV
Over the past decade, several reports have suggested that HbA1c may not reflect average blood sugar levels in HIV positive people. These reports were based on a small number of patients or had study designs that may be prone to biased interpretations, such as retrospective studies. So researchers in the United States conducted a prospective study in which volunteers were recruited specifically to assess blood sugar levels. Researchers recruited 100 HIV positive people who had diabetes or pre-diabetes and a group of 200 HIV negative people who had diabetes. This latter group acted as a control or comparison group. The researchers found that HbA1c can underestimate blood sugar levels in HIV positive people, possibly because of some anti-HIV medicines.
The 200 HIV negative people were of similar age, ethnicity and gender as the 100 HIV positive people recruited for this study. The average profile of the HIV positive people was as follows:
- 30% female, 70% male
- age -- 52 years
- length of HIV infection -- 14 years
- taking HAART -- 78%
- having a viral load less than 50 copies -- 61%
- having type 2 diabetes -- 77%
Participants had their blood drawn after fasting.
To their dismay, the researchers found that HbA1c results in HIV positive people were around 6.7% -- this should have reflected blood sugar levels between 4 and 7 mmol/l. However, direct assessments of blood sugar found that they were higher, nearly 9 mmol/l.
A statistical analysis taking many factors into consideration linked two things to the discordance between HbA1c results and actual blood sugar levels:
- use of abacavir (Ziagen, and in Kivexa or Epzicom)
- the size of red blood cells
The research team was at a loss to explain why this linkage occurred. Abacavir use has not been linked to altered HbA1c or to the size of red blood cells (RBCs).
After leaving the bone marrow, RBCs live for about four months and any health condition or drug that decreases their lifespan or affects their growth and development might affect the usefulness of HbA1c assessments. Medications such as sulpha-containing antibiotics -- Bactrim/Septra (trimethoprim-sulfamethoxazole) -- can affect the health of the bone marrow, where RBCs are produced, distorting the size of these cells, shortening their lifespan and ultimately affecting HbA1c test results.
The antiviral drug ribavirin is used as part of treatment for hepatitis C virus infection. There have been reports of HbA1c interference in some users of ribavirin. This is not surprising, as ribavirin can shorten the life of RBCs.
French researchers previously analysed different anti-HIV regimens and their possible impact on HbA1c in 249 patients. They found a statistical link between the use of the following drugs and mild bone marrow damage leading to altered HbA1c:
- AZT (Retrovir, zidovudine and in the fixed-dose combinations Combivir and Trizivir)
- d4T (Zerit, stavudine)
- 3TC (lamivudine and in the fixed-dose combinations Combivir and Kivexa)
Although 84 patients had taken abacavir in the French study, there was no link between abacavir use and the development of bone marrow damage.
In the present American study, researchers conducted other tests to find out if RBCs were being damaged, but no such damage was detected, which adds to the mystery of their findings.
Further research is needed to understand the American researchers' results. Such research needs to check for liver disease and the use of sulpha-containing medicines and ribavirin, all of which may have a negative impact the health of RBCs. The study should also assess intake of vitamins C and E, which may prolong the lifespan of RBCs.
What to Do?
In HIV negative people, HbA1c is commonly used as part of regular laboratory monitoring of blood sugar. An alternative test is fructosamine, which assesses levels of sugar on the protein albumin. The cost of this test is similar to that of HbA1c. While HbA1c can be done every three months, fructosamine needs to be done every two to three weeks. In the present American study, fructosamine measurements were strongly linked to accurate assessments of blood sugar levels in HIV positive people. Therefore, the U.S. team suggests that the use of fructosamine "may be an appropriate alternative" for assessing blood sugar levels over time in HIV positive people.
- Diop ME, Bastard JP, Meunier N, et al. Inappropriately low glycated hemoglobin values and hemolysis in HIV-infected patients. AIDS Research and Human Retroviruses. 2006 Dec;22(12):1242-7.
- Polgreen PM, Putz D, Stapleton JT. Inaccurate glycosylated hemoglobin AIc measurements in human immunodeficiency virus-positive patients with diabetes mellitus. Clinical Infectious Diseases. 2003 Aug 15;37(4):e53-6.
- Kim PS, Woods C, Georgoff P, et al. A1c underestimates glycemia in HIV infection. Diabetes Care. 2009 Sep;32(9):1591-3.