Treating insulin resistance and diabetes

NAM Publications HIV & AIDS Information :: Diabetes

Insulin resistance is seen in ‘Syndrome X’ a metabolic disorder with similar symptoms to HAART-associated lipodystrophy that occurs in HIV-negative people. Syndrome X may be corrected in some cases by the restoration of insulin sensitivity, using an anti-diabetes drug called metformin.

There is now evidence that metformin may be effective in reducing insulin resistance and abdominal fat in HIV-infected people on HAART. French doctors reported that metformin reduced insulin resistance, reduced triglyceride levels and improved abdominal fat distribution in a randomised study of 25 people receiving PIs.1 HIV wasting expert, Dr Carl Grunfeld, has also reported that metformin has shown the best results in the treatment of HAART-associated insulin resistance and diabetes, producing an associated decrease in body fat.

There is also evidence from randomised, controlled studies which suggests metformin is an effective treatment for insulin resistance and diabetes, and related metabolic and body fat disorders, seen in HIV-infected people on treatment. For instance, a team from Boston conducted a randomised, controlled study of metformin in 26 HIV-infected individuals with fat redistribution, high insulin levels and/or abnormal glucose tolerance. After three months, insulin levels, weight and blood pressure fell significantly in those treated with metformin compared to controls. The treated group also experienced a reduction in waist size and reduced visceral abdominal fat. 2

A randomised, placebo controlled comparative study of metformin or gemfibrozil in patients with abdominal fat accumulation and triglyceride levels above 5.2mm found that after one year of treatment, there was no significant improvement in fat redistribution, triglyceride levels or insulin resistance, nor was there any difference between the arms. 3 This study should be treated with caution because of the small numbers involved 15 in each arm.

A third study randomised 37 individuals with baseline fasting insulin level of above 104pmol/l and evidence of fat redistribution to receive metformin at a dose of 500mg twice daily, with dose escalation to 850mg twice daily after two weeks, or the same metformin regimen in combination with an exercise programme consisting of an hour of cardiovascular and weight training three times a week for twelve weeks. The two groups of patients had comparable insulin profiles and cardiovascular disease risk factors at baseline.

Patients in the exercise arm experienced a greater fall in their median systolic (p = 0.012) and diastolic (p = 0.001) blood pressure than individuals in the metformin only arm. In addition, the waist-to-hip ratio improved to a greater extent in the exercise/metformin arm than in the metformin-only arm, as did the fasting insulin (p 4

The British HIV Association guidelines recommend that insulin resistance should be treated with metformin.

The new class of anti diabetes drugs called glitazones, discussed above, may also be effective for treating diabetes or insulin resistance in HIV-positive people. The glitazones are unlikely to interact with PIs and studies to determine the efficacy of glitazones in the treatment of PI-related diabetes are ongoing (see above).

Discontinuing protease inhibitor treatment may also reduce insulin resistance. 5

Human growth hormone (HGH) can also restore insulin sensitivity, and some researchers believe that disruption of insulin-like growth factor 1 and HGH production within the body is at the root of the disorders now being seen. However, HGH may precipitate diabetes in a small proportion of people.

Mineral and vitamin supplements may protect against diabetes in the general population 6 but whether supplements have a protective effect in people taking antiretroviral treatments is unknown.

References
1. SaintMarc T et al. Effects of metformin on insulin resistance and central adiposity in patients receiving effective protease inhibitor therapy. AIDS 13: 10001002, 1999a
2. Hadigan C et al. Metformin in the treatment of HIV lipodystrophy syndrome: a randomized controlled trial. JAMA 284: 472477, 2000
3. Martinez E et al. A randomized, double-blind, placebo-controlled, comparative study on the effects of metformin or gemfibrozil in lipodystrophic HIV1infected patients receiving protease inhibitors (PI). Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 702T, 2002
4. Driscoll SD et al. Effects of exercise training and metformin on body composition and cardiovascular indices in HIV-infected patients. AIDS 18: 465 473, 2004
5. Walli RK et al. Improvement of HAART-associated insulin resistance and dyslipidemia after replacement of protease inhibitors with abacavir. Eur J Med Res 6(10):413421, 2001
6. Ford ES et al. Vitamin supplement use and diabetes mellitus incidence among adults in the United States. Am J Epidemiol 153: 892897, 2001

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