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Lipodystrophy

posted Dec 4, 2013, 7:09 AM by Ewa Rakowski   [ updated Dec 4, 2013, 8:33 AM ]

A new Monte Minute from our RAT rotator Stephanie Behringer:

At a recent COS Victoria presented an interesting case of a 45 year old woman with diabetes and HIV on ART who presented to the ED with severe abdominal pain, nausea and vomiting. Laboratory work up revealed a highly elevated lipase of 11,794 U/L, a total cholesterol of 1,196 mg/dL and triglycerides of 8,046 mg/dL! A pretty straightforward diagnosis of hyperlipidemia induced acute pancreatitis. But what caused this patient’s lipids to become so elevated?

Further work up revealed that this patient had a combination of severe mixed familial hyperlipidemia as well as HIV related lipodystrophy, uncontrolled diabetes mellitus (A1c12.4%) and a poor diet, all of which led to her presentation to the hospital.

So let’s talk about adipose tissue and lipodystrophy for a moment:

Adipose tissue – does it “do” anything?
In humans, adipose tissue is located beneath the skin, around internal organs, in bone marrow and in breast tissue. It provides insulation from heat and cold as well as protective padding and is an important reserve for lipids, which can be burned if we need fuel for muscular contractions or general metabolism. 

There is a constant flux of free fatty acids entering and leaving adipose tissue. The net direction of the flux is controlled by insulin and leptin. If insulin is elevated, there is a net inward flux of free fatty acids and only when insulin is low can free fatty acids leave adipose tissue. 

In recent years, adipose tissue has also been recognized as a major endocrine organ. It produces leptin, estrogen, resistin, adiponectin and cytokines among others. 

Leptin is one of the most important adipose derived hormones and plays a key role in regulating energy intake and expenditure, including hunger and appetite, metabolism and behavior. An imbalance of this finely orchestrated system causes severe metabolic complications, which you may see in people with lipodystrophy.

Lipodystrophy – what exactly is it?
Lipodystrophy is a degenerative condition of the body’s adipose tissue and represents a group of rare, heterogenous disorders characterized by progressive loss of adipose tissue, mainly from the subcutaneous compartment and occasionally from visceral fat.
The word is derived from the greek “lipos” (fat) and “dys-” (bad/ill) and “trophe” (nourishment) and sometimes is also referred to as “fat redistribution syndrome”. There are two main types of lipodystrophy, congenital and acquired, each of which can be broken down into two subtypes; generalized or partial. 

The drop in hormone levels such as leptin from loss of adipose tissue correlates with the extent of fat loss and leads to a variety of metabolic complications. 

Clinically, patients with severe lipodystrophy have insulin resistance, which leads to diabetes mellitus, excessive lipolysis and high serum free fatty acid concentrations. Excessive lipolysis also drives VLDL production and blocks chylomicrone clearance, which then in combination with the above mentioned, leads to acute pancreatitis, hepatic steatosis, PCOS, atherosclerosis, HTN, CAD, strokes, CKD etc, you name it. 

Physical changes may include hypertrophy of adipose tissue over cervical vertebrae (buffalo hump), shoulders, abdomen and breasts and atrophy of fat in the face, extremities and buttocks. Others might have little visible fat and may appear very muscular.

Back to the case
So what accounted for our patient’s severe lipodystrophy? Likely a combination of several things. 

  • For one, she was found to have elevated Apo-B levels which suggests that she has familial combined hyperlipidemia. - Another major culprit was the protease inhibitor ritonavir (Norvir) that this patient was taking. Protease inhibitors are frequently associated with severe lipodystrophy. 
  • In some cases, lipodystrophy can also be seen in patients with HIV who are not taking protease inhibitors. This is not to be confused with AIDS wasting syndrome, which occurs at late stages of HIV/AIDS and is characterized by muscle atrophy, diarrhea, extreme weakness and fevers. 
  • Furthermore, our patient also had poorly controlled diabetes mellitus which caused her to be in a catabolic state. 
  • Last but not least, her food choices were not exactly healthy. 

Luckily, she did not need plasmapharesis and her clinical picture improved on an insulin drip. She was discharged home on a statin, a fibrate, metformin, insulin, a TZD (which not only treats diabetes, but also aides in adipogenesis), vitamin C + E (to prevent further episodes of pancreatitis – interesting!) and of course, instructions for a healthier diet. She is currently undergoing work up for possible leptin replacement therapy.


Take Home Messages
- Lipodystrophy, is a severe metabolic disorder that is strongly associated with protease inhibitor treatment and requires a multidisciplinary approach.
- In severe combined HLD, think of familial lipid disorders and don’t forget to test other family members, as well.

I hope you enjoyed learning about this case as much as I did. Don’t let it prevent you from culinary indulgences over the holidays. Happy holidays everybody!

Ċ
Ewa Rakowski,
Dec 4, 2013, 7:09 AM
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