Important note: Information in this article was accurate in October 2000. The state of the art may have changed since the publication date.
Some PHAs have developed changes in body shape involving loss of fat and or muscle. Still others have experienced an increase in fat. As well, there are people who develop high levels of insulin, sugar and fatty substances in their blood. Collectively, these symptoms have been lumped together and called the lipodystrophy syndrome. Readers should be aware that there may be several different syndromes taking place at the same time in HIV+ people. In many cases it appears that the changes in body shape as well as those affecting insulin, sugar and fat level in the blood appear to be related to the use of anti-HIV drugs. Protease inhibitors in particular seem to be associated with blood sugar problems. As a result, it is difficult for researchers to separate cause from effect. In this issue of TreatmentUpdate we focus on the increased levels of sugar and insulin found in the blood of PHAs with the lipdystrophy syndrome as well as ways doctors manage this complication.
The level of sugar (glucose) in the blood is carefully controlled by the body. After a meal the pancreas gland increases its production of the hormone insulin. Increased insulin levels stop the liver from pouring more sugar into the blood. Insulin also allows muscle and other cells to remove glucose from the blood so that they can "burn" this sugar for energy.
In PHAs treated with protease inhibitors (PI) it appears that cells don't respond normally to insulin - levels of sugar in the blood remain higher than normal. Such a condition is called insulin resistance. In an attempt to reduce high levels of sugar in the blood, the pancreas produces increasing amounts of insulin. Eventually even very high levels of insulin fail to drive down sugar levels and diabetes develops.
It is interesting that in non-HIV-infected people blood sugar problems usually are associated with the following complications:
In HIV-positive people the link between all of these complications also exists, particularly in people with the lipodystrophy syndrome.
Lack of regular exercise and being overweight are connected. Moreover, these two factors also increase the risk of heart disease and diabetes. Therefore, changes to the diet and an exercise program (where possible) can help some people decrease their risk of heart disease and diabetes. If diet and exercise don't help then doctors can prescribe oral medications or even injections of insulin to help lower blood sugar.
In the case where people have been diagnosed with type 2 diabetes, which does not require injections of insulin, here is a list of the three main types of drugs which may be prescribed:
According to one review, sulfonylureas or metformin are equally effective at reducing levels of sugar in the blood. However some doctors may prefer metformin because it also helps people lose weight, usually fat. As well, metformin also can reduce levels of fatty substances in the blood.
The glitazones are a new group of drugs. The first glitazone was Rezulin (troglitazone). Unfortunately Rezulin was associated with the development of "severe and unpredictable" liver damage. In the United States at least 61 people have died because of liver damaged linked to use of Rezulin. As a result, this drug has been withdrawn in the US and UK.
Newer glitazones such as Actose (pioglitazone) and Avandia (rosiglitazone) appear to work well at reducing blood sugar levels. Although these drugs may be safer than Rezulin, they may not be safe for use by people with pre-existing liver or heart damage. In theory Actose may interact with protease inhibitors (PIs)and non-nukes (delavirdine, efavirenz and nevirapine) reducing or raising the concentrations of PIs and non-nukes. Long-term studies of glitazones in PHAs are needed to study their safety in this population.
In this issue of TreatmentUpdate we review the short-term effect of metformin in HIV+ people as well as ways to deal with some of its side effects.
1. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 1999 Aug 17;131(4):281-303.
2. Périard D, Telenti A, Sudre P, et al. Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. Circulation 1999 Aug 17;100(7):700-5.
3. Hadigan C, Corcoran C, Basgoz N, et al. Metformin in the treatment of HIV lipodystrophy syndrome: a randomized controlled trial. JAMA 2000 Jul 26;284(4):472-7.
4. Forman LM, Simmons DA, Diamond RH. Hepatic failure in a patient taking rosiglitazone. Ann Intern Med 2000 Jan 18;132(2):118-21.
5. Al-Salman J, Arjomand H, Kemp DG, Mittal M. Hepatocellular injury in a patient receiving rosiglitazone. A case report. Ann Intern Med 2000 Jan 18;132(2):121-4.
6. Krentz AJ, Bailey CJ and Melander A. Thiazolidinediones for type 2 diabetes: new agents reduce insulin resistance but need long-term clinical trials. BMJ 2000 Jul 29;321(7256):252-3.
7. Schütt M, Meier M, Meyer M, et al. The HIV-1 protease inhibitor indinavir impairs insulin signalling in HepG2 hepatoma cells. Diabetologia 2000 Sep;43(9):1145-8.
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