Type II diabetes in HIV disease

NAM Publications HIV & AIDS Information :: Diabetes

The development of type II diabetes has been reported in 2 to 10% of people on antiretroviral therapy (ART), with prevalence growing as time on therapy increases. In the general population, prevalence rates are around 6% and increasing each year.

Type II diabetes is the form of diabetes that develops in adults because of a gradual decline in insulin sensitivity and insulin production. Insulin is the hormone that regulates levels of glucose in the blood and uptake of glucose into various tissues. Glucose is needed by cells for energy.

Over time, cells may be less able to take up the glucose that builds up in the bloodstream after a meal. When this happens, people are said to be insulin resistant, which means that they require more insulin to maintain glucose levels within a normal range. As insulin resistance increases, fat cells release fatty acids in a bid to supply the liver with more raw materials to make glucose, but this fails to restore normal levels of glucose.

Eventually, glucose levels will increase to a point where physical symptoms of hyperglycemia (high blood sugar) occur. These include:

  • Fatigue.
  • Frequent urination, due to the need to get rid of excess glucose.
  • Constant thirst due to loss of fluid.
  • Blurred vision.
  • Weight loss.

Problems that are more serious can emerge in cases of severe type II diabetes, such as:

  • Lesions in the retina of the eye.
  • Kidney disorders (diabetic nephropathy).
  • Nerve damage, especially in the legs (diabetic neuropathy).
  • Impotence.
  • Bacterial or fungal skin infections.
  • Cardiovascular disease (angina, stroke, heart attack).

Risk factors for diabetes include:

  • Increasing age.
  • Male gender.
  • Black race.
  • Increasing body mass index, abdominal obesity, and/or general obesity.
  • Hepatitis C coinfection.
  • Lipodystrophy and/or metabolic syndrome.
  • Uncontrolled hypertension.

Diabetes substantially increases the risk of heart disease, in part because when large amounts of glucose are present in the blood, the sugar becomes attached to low density lipoprotein (LDL) or ‘bad’ cholesterol. As a result, cholesterol is oxidised more easily and taken up into the wall of blood vessels, where it forms plaques that contribute to hardening of the artery and eventual heart disease.When sugar attaches to high density lipoprotein (HDL) or ‘good’ cholesterol, the liver has a more difficult time removing cholesterol from the bloodstream. High glucose levels also increase blood coagulation and reduce the flexibility of blood vessels, both contributory factors in the development of cardiovascular problems.

An analysis of the prevalence and incidence of blood glucose abnormalities in men enrolled in the Multicenter AIDS Cohort Study (MACS), found that the risk of prevalent and incident fasting hyperglycemia was two to three times greater, and the risk of diabetes was four to five times greater in HIV-positive men on HAART compared with HIV-negative men. Use of antiretroviral therapy was associated with a significantly increased risk of hyperglycemia, but other factors, including HIV disease severity and CD4 cell count may also play an important role.1 In the D:A:D (Data Collection on Adverse Events of Anti-HIV
Drugs) cohort, incidence of diabetes mellitus increased with cumulative exposure to antiretroviral therapy. An association remained after adjusting for potential risk factors, CD4 count, lipids, and lipodystrophy. The strongest association found was between diabetes and exposure to either d4T (stavudine) or AZT (zidovudine). Investigators posit that thymidine analogues, through mitochondrial toxicity, contribute directly to insulin resistance.2

D:A:D investigators also found that in individuals with preexisting diabetes, there was 2.4 increased risk of a coronary event as compared to those without diabetes.3

Co-infection with hepatitis C appears to further increase the risk of diabetes and hyperglycemia in HIV-positive people, according to data from the United States Department of Veterans’ Affairs and the team at Johns Hopkins University.4 5 Hepatitis C coinfection may be especially important in patients over 40 years of age, as may a history of acute pancreatitis.6

See Treating body fat and metabolic changes – switching drugs in Side-effects for discussion of these studies.

References
1. Brown T et al. Prevalence and incidence of pre diabetes and diabetes in the Multi-center AIDS Cohort Study. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 73, 2004
2. DeWit S et al. Incidence and risk factors for new onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Diabetes Care 31(6):12241229, 2008
3. Worm SW et al. Diabetes mellitus, preexisting coronary heart disease, and the risk of subsequent coronary heart disease events in patients infected with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study). Circulation 119(6): 805811, 2009
4. Butt AA et al. HIV infection and the risk of diabetes mellitus. AIDS 23: 12271234, 2009
5. Mehta SH et al. The effect of HAART on HCV infection on the development of hyperglycemia among HIV-infected persons. Journal of Acquired Immune
Deficiency Syndromes 33: 577584, 2003
6. Crane H et al. History of acute pancreatitis and hepatitis C virus infection increase the risk of new onset diabetes among HIV-infected patients. Eleventh
Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 878, 2004

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