104
VOLUME 8 NUMBER 3 • SEPTEMBER 2011
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
HIV and diabetes
DOUGLAS WILSON
Correspondence to: Dr Douglas Wilson
Department of Medicine, Edendale Hospital and University of KwaZulu-Natal,
Pietermaritzburg
Tel: +27 (0)33 395-4146
e-mail:
S Afr J Diabetes Vasc Dis
2011;
8
: 104–105
S
outh Africa is a rapidly urbanising society and has high levels of
obesity, with a burgeoning epidemic of type 2 diabetes.
1,2
This
phenomenon is occurring in the context of one of the worst
HIV pandemics in the world, associated with extraordinarily high
mortality in young adults.
3,4
Antiretroviral therapy has transformed
the management of HIV infection in South Africa, but as patients
living with HIV gain weight and survive into middle age, they are at
significant risk of developing type 2 diabetes.
5
If not treated appropriately, patients living with both these
chronic conditions develop serious target-organ damage,
notably atherosclerosis, chronic renal impairment and peripheral
neuropathy. Sight-threatening retinopathy, commonly affecting
patients with diabetes, is usually caused by opportunistic infections
(such as cytomegalovirus) in patients living with HIV and is best
prevented by timely initiation of antiretroviral therapy.
Antiretroviral therapy is associated with dyslipidaemia,
lipodystrophy, insulin resistance and glucose intolerance.
6
The
underlying reasons for these observations remain to be fully
elucidated, but persisting systemic inflammation may contribute
to the development of the diabetic state.
7
Lipodystrophy is
associated with reduced levels of apidonectin, leptin, and abnormal
growth hormone secretion.
8-10
The intra-abdominal (visceral) fat
accumulation component of lipodystrophy is particularly associated
with insulin resistance and diabetes.
11-13
Lipid abnormalities most often seen are elevated triglycerides,
total cholesterol and low-density lipoprotein cholesterol, and low
high-density lipoprotein cholesterol.
14,15
Additionally, HIV infection
causes endovascular inflammation. The commonest end result
of these abnormalities is atherosclerosis, and patients with HIV
infection and diabetes are at increased risk of myocardial infarction
and stroke.
16,17
The antiretroviral drugsmost often associatedwith dyslipidaemias
are stavudine, zidovudine, efavirenz, lopinavir/ritonavir and
the ‘earlier’ protease inhibitors. Abacavir is associated with an
increased risk of myocardial infarction. Those with a ‘cleaner’ lipid
profile include lamivudine, emtricitabine, nevirapine, tenofovir and
atazanavir.
The approach to lipid abnormalities begins with dietary
modification, followed by medication. Drug interactions between
lipid-lowering drugs and antiretrovirals are common and consulting
a web-based resource is helpful (e.g.
.
org). In general, low-dose atorvastatin, pravastatin, the fibrates and
niacin are safe to use with the protease inhibitors.
18,19
Diagnosis of diabetes in HIV-infected patients follows established
international guidelines, i.e. an HBA
1c
level of > 6.5%. The
management strategies are similar for HIV infection and diabetes.
Lifestyle modification, healthy eating, exercise, support from
family and friends, knowledge of the illness and medications, and
scrupulous adherence to treatment regimens are fundamental to
both conditions.
20
Glucose intolerance is managed with diet and exercise, weight
loss and metformin. There is a theoretical risk of lactic acidosis due
to metformin but this does not preclude using metformin with
standard antiretroviral drugs in patients with normal renal function.
Pioglitazone has been shown to have beneficial effects in patients
with antiretroviral-induced lipo-atrophy and could rationally be
combined with metformin for the management of diabetes in HIV-
infected patients taking antiretroviral therapy.
21,22
Importantly, pioglitazone increases fracture risk in post-
menopausal woman, and tenofovir reduces bone density.
Measuring bone density in patients taking both drugs, with a view
to preventing fractures should be considered. Exenatide has not
been specifically studied in patients living with HIV.
Subcutaneous insulin should be initiated as soon as it becomes
apparent that diet, weight loss and oral agents are not achieving
therapeutic goals (i.e. HBA
1c
level of < 7%).
23
All patients with
diabetes should receive aspirin, a statin and an ACE inhibitor or
angiotensin receptor blocker (which also reduces the risk of HIV
nephropathy).
24
Glucose control should be monitored with home capillary blood
testing and measurement of HBA
1c
levels. Interestingly, in patients
on antiretroviral therapy, the HBA
1c
level may slightly underestimate
the degree of glycaemia but the clinical relevance of this observation
is uncertain.
25
Type 1 diabetics are a challenging group of patients, who often
become HIV infected during adolescence. Management of the
two conditions is along established lines, but these patients need
significant counselling and support to address high-risk behaviour,
non-adherence to medications, and issues of sexuality and body
image. The need for rigid adherence to both insulin therapy and
antiretroviral therapy can be especially problematic for these
patients.
26
References
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1.
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Publ Hlth Nutr
2005;
8
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Idemyor V. Diabetes in sub-Saharan Africa: health care perspectives, challenges,
2.
and the economic burden of disease.
J Natl Med Assoc
2010;
102
: 650–653.
Statistics South Africa. Mortality and causes of death in South Africa 2007:
3.
finding from death notification 2009.
/
statsdownload.asp?PPN=P0309.3&SCH=4507
National Department of Health, South Africa (2007) The national HIV and syphilis
4.
survey, South Africa.
Samaras K, Wand H, Law M, Emery S, Cooper D, Carr A. Prevalence of metabolic
5.
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using International Diabetes Foundation and Adult Treatment Panel III criteria:
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Diabetes Care
2007;
30
: 113–119.
Fisher SD, Miller TL, Lipshultz SE. Impact of HIV and highly active antiretroviral
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