UC Davis researchers find increased diabetes risk in HIV-positive children
Some antiretroviral therapies also associated with increase in cholesterol levels
UC Davis researchers have found that, despite results to the contrary in adults, average cholesterol profiles in young children with HIV do not worsen when they are put on highly active antiretroviral therapy (HAART) — but only when certain combinations of drugs are used. The researchers also found that children beginning or switching to HAART also showed an increase in insulin resistance, potentially raising their risk of developing diabetes later in life.
"These children are facing a lifetime of potential complications, not just from their HIV infection, but from the drugs used to treat it," said Caroline Chantry, associate professor of pediatrics.
The study is the largest to date looking at metabolic disruption caused by HIV and associated treatment in children before puberty.
"We need to know now if these children will be at greater risk of developing heart disease or diabetes so that we can improve treatment and focus on prevention," Chantry said.
The current study was published online by Pediatrics.
The good news for patients, based on the current study, is that increasing CD4 T-cell counts — a measure of immune function used to gauge success of HAART — results in improvements in cholesterol levels. Their risk of diabetes, however, remains a concern because the children involved in the study showed increases in their bodies' resistance to the action of insulin, the hormone responsible for stabilizing blood glucose levels.
"The values were not so high as to diagnose them with diabetes, but insulin resistance is a risk factor for developing the disease," Chantry said. The issue will require further study, she added.
"We need to know now if these children will be at greater risk of developing heart disease or diabetes so that we can improve treatment and focus on prevention."
—Caroline Chantry, UC Davis pediatric specialist.
Chantry and her colleagues also discovered that improved lipid profiles paralleled improved sensitivity to growth hormone. This provides a clue to a possible cause of abnormal cholesterol in the infected children that could eventually lead to better treatment or prevention strategies. Children with HIV often suffer from stunted growth as a result of growth hormone resistance.
There is other good news with respect to the study's cholesterol findings, Chantry said. Physicians can further reduce their pediatric patients' risk of developing high cholesterol by simply changing the combination of drugs they are given as part of HAART. Children in the study had worse cholesterol profiles (lower levels of HDL, the so-called "good" cholesterol, and a higher total to HDL cholesterol ratio) when a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor were used in combination, but not when either was used alone.
Previous studies had shown that adults and teenagers on HAART commonly showed increases in cardiovascular risk because of increased LDL levels and in insulin resistance. Chantry and her colleagues decided to take a look at these metabolic disturbances in younger patients.
The 97 children included in this study were part of the Pediatric AIDS Clinical Trials Group Protocol 1010, a multi-state 48-week observational study. They ranged in age from less than one-month to less than 13 years and had predominantly mild-to-moderate disease. To be included, the children had to either be starting HAART for the first time or changing treatment because other therapies had failed.
Blood samples were taken during the study. Fasting cholesterol, glucose, insulin and CD4 T-cells were among the blood levels measured. To analyze the data, each child was matched for age, gender and race/ethnicity with data from children in the National Health and Nutrition Examination Survey.
Researchers found that initiation or change in HAART in these children was associated with significant increases in T-cell counts, both bad (LDL) and good cholesterol (HDL) measures, sensitivity to growth hormone, and insulin resistance.
"We were very surprised to find out that overall cardiovascular risk does not increase for these children starting or switching HAART," Chantry said. The results showed that both HDL (good) and LDL (bad) cholesterol, increased, but the good more so than the bad. "There were some good changes and some not-so-good changes, but the net effect was no increased risk," she added, "and some children actually improved."
Doctors use a variety of combinations in HAART that can include one or the other or both of the classes of drugs known as protease inhibitors and non-nucleoside reverse transcriptase inhibitors. "The combinations that have both classes were worse for the patients in terms of lipid profiles," Chantry said. "Either one of these classes along with other types antiretrovirals is better than both together."
Keeping children with HIV healthy for as long as possible means looking at the way they are affected by the drugs used to treat them, Chantry said. "Children are not little adults. We are never sure until we look whether or not what is medically going on in adults is also going on in children."
UC Davis Children's Hospital is the Sacramento region's only comprehensive hospital for children. From primary care offices to specialty and intensive care clinics, pediatric experts provide compassionate care to more than 100,000 children each year and conduct research on causes and improved treatments for conditions such as autism, asthma, obesity, cancer and birth defects. For more information, visit the UC Davis Children's Hospital Web site.