Defining lipodystrophy

Lipodystrophy is a syndrome characterised by abnormal fat distribution and metabolic disturbances in the way the body processes fats (lipids) and glucose. Depending on its severity, lipodystrophy can increase someone's risk of diabetes and cardiovascular disease.

HIV-related lipodystrophy includes two distinct phenomena: lipoatrophy (subcutaneous fat loss) and fat accumulation (lipohypertrophy). Although some patients may experience both problems, the two conditions are not necessarily part of a single syndrome.

Lipoatrophy involves loss of fat in the face, extremities (especially the legs), buttocks, and subcutaneous tissue of the abdominal area. It can lead to a wasted appearance and must be differentiated from HIV-associated wasting, which involves loss of muscle mass as well as fat.

Fat accumulation (lipohypertrophy) can present with increased intra-abdominal (visceral) fat, formation of a dorsocervical fat pad ('buffalo hump'), or accumulation of fat in the neck, breasts, or other areas.

Fat accumulation must be differentiated from obesity, which can occur when patients with HIV infection are started on antiretroviral therapy and become healthier. Fat accumulation is often accompanied by insulin resistance, though lipoatrophy can also lead to insulin resistance. Both lipoatrophy and fat accumulation can be associated with lipid abnormalities.

The term 'lipodystrophy' has been used in some cases to refer to the presence of lipoatrophy and/or fat accumulation, as well as to the combination of these morphologic changes and metabolic abnormalities. Originally regarded as a direct consequence of protease inhibitor treatment, the etiology of lipodystrophy is not that straightforward. Different antiretroviral agents and specific drug classes, as well as other factors (such as age, gender, race, and disease status) are implicated to varying degrees.

The physical changes often cause the most distress. The change in body shape is usually unwelcome and can, in some cases, signal someone's HIV status. Fat loss or wasting (lipoatrophy) occurs in the face (sunken cheeks), arms, legs, and buttocks. Fat deposits can appear and increase the size of the breasts, cervicodorsal fat pad (resulting in 'buffalo hump'), and abdomen.

Metabolic changes may have serious long-term consequences for the body. High levels of cholesterol in the blood and increased triglycerides raise the risk of heart disease, stroke, and hypertension. An inability to respond to or use the insulin the body produces can lead to the development of type 2 diabetes, which in itself nearly doubles the risk of a vascular event by two to four-fold. Lactic acidosis (occurring when lactic acid builds up in the bloodstream faster than it can be removed) can cause pain, loss of energy, fatigue, and shortness of breath.