Metabolic Disorders and Women

Debra Johnson, NP, PA-C
Judith Currier, MD

This is the first part of a two part series.

Part 1

Patients with HIV infection and the clinicians caring for them have recently been expressing interest in the possible long-term effects of the potent anti-retrovirals currently in use. Reports of new-onset diabetes mellitus, abnormal distribution of body fat, and hyperlipidemia (increase in cholesterol, decrease in HDL, increase in LDH and increase in triglycerides) occurring during treatment with Highly Active Antiretroviral Therapy (HAART) have gained widespread attention. Little is known about why this happens, whether its directly related to protease inhibitors, what to do about these new findings, and what the long-term health implications of these abnormalities are in the HIV-infected population. Also unknown is what differences there are, if any, in women compared to men relative to these metabolic abnormalities.

What is hyperlipidemia?

Hyperlipidemia in individuals taking HAART has been reported, sometimes to extremely high levels, in excess of 1000 mg/dl. Hypertriglyceridemia was recognized as a complication of HIV disease prior to the era of protease inhibitors. Current reports indicate that elevated levels of triglycerides have occurred in individuals having positive clinical and virologic responses (decrease in viral load and increase in T-cells) to HAART.

What are Cholesterol and Triglycerides?

Cholesterol is an essential part of cell membranes and a major part of brain and nerve cells. High concentrations are also found in the adrenal glands, Cholesterol is an important part of bile acids and sex hormones. Triglycerides are used in the body mainly to provide energy for different metabolic processes.

Lipoproteins (LDL and HDL) are best known as the vehicles that help transport triglycerides and cholesterol throughout the bloodstream. There are two types of lipoprotein; LDL which is low-density lipoprotein, (the bad cholesterol) and HDL which is high-density lipoprotein (the good cholesterol). LDL is released by the liver and is rich in triglycerides and cholesterol. LDL delivers triglycerides to fat and muscle cells. LDL transports triglycerides back to the liver and to the fat cells (adipose tissue). HDL acts as a scavenger which carries unwanted, excess cholesterol, partly from cell breakdown, back to the liver where the cholesterol is excreted in bile salts or removed by receptors on the liver. This process helps rid the body of cholesterol and prevents lipid accumulation in the arterial wall. When HDL is too low, LDL increases and may lead to atherosclerosis which over the long term may lead to blockages that causes myocardial infarction or stroke.

What is abnormal fat distribution?

Several terms have been used to describe various alterations in body fat distribution, including protease paunch, Crix belly,buffalo hump and lipodystrophy. Some of these abnormal findings were observed before the use of protease inhibitors, raising the possibility that a factors other than protease inhibitors may be involved.

Abnormal collection of fat in the back of the neck and upper back "buffalo hump" has been associated with protease inhibitor treatment, but also reported in some patients not on a protease inhibitors. Surgical excision or liposuction has been tried but recurrences have been reported.

Protease paunch and Crix belly are terms for the abnormal abdominal fat that has been reported with protease inhibitors. Increases in triglycerides have also been reported with this visceral fat deposition. In some patients with abnormal fat redistribution and insulin response has been noted (so called insulin resistance). Loss of fat in the extremities has also been reported. Studies collecting objective measures of body composition, using dual-energy x-ray absorptiometry (DEXA scanning) and MRIs (magnetic resonance imaging) along with measurements of the chest, abdomen, hips, thigh, hip-to-waist ratio and BIA (bioelectrical impedence analysis) are currently underway.

High blood sugar

Hyperglycemia is an elevation in blood sugar. Reports of hyperglycemia have occurred with all of the protease inhibitors. However, this side effect continues to remain an uncommon complication of protease inhibitors occurring in approximately 4% of all those patients taking these drugs. The mechanism of this hyperglycemia is not clearly understood, but there seems to be a positive response to diet and medications.

There have been a few reports of patients who developed hyperglycemia during treatment with protease, who stopped their protease inhibitors, but continued their nucleosides and had a spontaneous resolution of their high blood sugar.

Diet modification is the first line of treatment for mild increases in blood sugar. In those patients whose blood sugar can not be controlled with diet and exercise, a hypoglycemic medication should be added. In extreme situations, insulin may need to be added to control otherwise uncontrollable blood sugars.

Debra Johnson, NP,PA-C is Clinical Investigator for the USC Clinical Trials Unit/ KECK School of Medicine Clinical Instructor for AETC (AIDS Education Training Center)Primary Care for 450 HIV/AIDS patients