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Insulin Resistance and Diabetes

Part of A Practical Guide to HIV Drug Side Effects


Protease inhibitors have been tied to an increased incidence of glucose intolerance and decreased sensitivity to insulin, the hormone that is needed for the uptake of glucose (sugar) into the body's cells. When that process isn't working properly, glucose remains in the bloodstream, creating the high blood sugar that can cause damage to the blood vessels, and, ultimately, diabetes, with its list of possible complications, including:

  • kidney failure
  • blindness
  • cardiovascular problems from top (strokes) to bottom (amputations) and in between (heart attacks)

So far, the rate of development of diabetes in PHAs is relatively low, but researchers fear it will increase over time. It is important to watch for the classic warning signs of diabetes:

  • excessive thirst
  • abnormal hunger
  • increased urination

With any of these, call your doctor immediately so that diagnostic tests can be run.

You may be at increased risk for diabetes if:

  • You have a family history of diabetes.
  • You are overweight.
  • You live a couch-potato lifestyle.

Recent research shows that indinavir (Crixivan), amprenavir (Agenerase) and ritonavir (Norvir) -- and probably all the other protease inhibitors -- may have specific effects that will cause blood sugar problems. The researchers, noting that other studies have shown that insulin
resistance appears prior to the appearance of lipodystrophy symptoms, predict that insulin resistance may occur much earlier than has been so far reported, may be far more widespread, and may be implicated in the development of lipodystrophy.

Tips for Handling Insulin Resistance

Substituting a non-nucleoside analogue or a nucleoside analogue for a protease inhibitor (PI) has been suggested as a possible way to improve insulin sensitivity. The switch studies done to date have been somewhat conflicting, but there is some evidence that switching from a PI to either the non-nuke nevirapine (Viramune) or the nuke abacavir (Ziagen, ABC) may improve insulin sensitivity and lower glucose. Results with a switch to the non-nuke efavirenz (Sustiva) have been less clear, with one study showing improvement and another not. Much more research will be required to determine what may be best in this regard. It will be very important to take into account the treatment history for anyone considering switching drugs, since some people may really need the PI(s) to maintain viral control.

For anyone with elevated insulin levels (indicating insulin resistance) or elevated blood sugar levels, it definitely couldn't hurt to do the things that normally help to increase insulin sensitivity, including the following:

  • regular progressive resistance exercise (like weight-training) and a cardio workout
  • weight loss in those who are significantly overweight -- obesity alone is a serious risk factor for adult-onset diabetes
  • limiting sugar and refined carbohydrate intake (white starchy foods, white sugar and flour and all the foods made with them)
  • eating a more nutritious diet that is higher in fibre (found in whole-grain foods and fruits and vegetables) and lower in polyunsaturated fats (found in most vegetable oils and many prepared foods; it's best to stick with monounsaturated oils like olive oil) has been shown to be tied to improved insulin sensitivity
  • testosterone replacement therapy in men, where needed
  • supplementation with a potent multiple vitamin/mineral that contains the B complex vitamins (especially B6), antioxidants (especially alpha-lipoic acid) and minerals (especially chromium) that help maintain normal cellular insulin sensitivity

It is important to have your blood sugar monitored regularly. If it begins to rise, and lifestyle modifications or drug switches are not enough to get blood sugar under control, antidiabetic medications may be needed. Two common drugs are rosiglitazone (Avandia) and metformin (Glucophage). Studies on the use of such drugs with protease-inhibitor-caused insulin resistance are limited but have shown improvements. However, there may be substantial drawbacks related to body fat loss (for more on this, see "Body Distortions").

Most expert groups are waiting for additional research before making official recommendations on approaches to handling insulin resistance and blood sugar problems in PHAs, but the British HIV Association now recommends the following for anyone with symptoms of glucose intolerance:

  • dietary advice and exercise
  • switching from a PI-based regimen to a PI-sparing regimen (in people taking their first regimen)

For more info on insulin resistance, see "La Dolce Vita" in the Spring/Summer 2005 issue of CATIE's Positive Side magazine, available at or by calling 1.800.263.1638 [if you're in Canada].

For more recommendations on how to handle glucose intolerance, go to the British HIV Association website at

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This article was provided by Canadian AIDS Treatment Information Exchange. Visit CATIE's Web site to find out more about their activities, publications and services.
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