112
VOLUME 9 NUMBER 3 • SEPTEMBER 2012
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Correspondence to: Dr Pranessa Govender
Department of Nephrology, Internal Medicine,
Greys Hospital, Pietermaritzburg
e-mail:
S Afr J Diabetes Vascular Dis
2012;
9
: 112–113
Diabetes and the metabolic syndrome in HIV
PRANESSA GOVENDER
W
hen the antiretroviral (ARV) rollout finally began in
2004,
it was a huge victory for the health sector and
South Africa.
1
Almost 10 years later, we find ourselves
facing new challenges in HIV-positive patients. As patients survive
longer into middle age with the use of antiretroviral therapy,
they are becoming more prone to non-HIV related diseases such
as type 2 diabetes, hypertension, dyslipidaemia and an increased
risk of cardiovascular disease. In the long term these conditions
are associated with significant morbidity and mortality and need
prompt diagnosis and treatment.
2
There are three categories of diabetic patients in the HIV-positive
population:
highly active antiretroviral therapy (HAART)-naïve, HIV-positive
•
patients who develop diabetes after becoming infected with HIV.
Diabetic patients who had diabetes prior to becoming HIV
•
infected.
HIV-positive patients who develop diabetes after antiretroviral
•
therapy has been initiated.
The time of HIV infection is difficult and almost impossible to
determine. Identifying more patients at the onset of HIV infection
would allow larger numbers of patients to be recruited and
studied for the effects of HIV on glucose homeostasis. There have
been several studies on the development of diabetes and insulin
resistance secondary to antiretroviral therapy. But there is limited
research on a possible link between HIV itself and the consequent
development of diabetes.
3
Insulin resistance may have an HIV disease-associated compo-
nent. Earlier studies show that HIV-infected HAART-naïve patients
may have higher rates of insulin clearance and increased insulin
sensitivity in peripheral tissues compared to a non-infected person.
4
Lipodystrophy occurs usually in patients on particular antiretroviral
drugs, but can occur in the ARV-naïve patient. There is evidence that
HIV 1 infection contributes to the development of the lipodystrophic
phenotype, interfering with some key genes of adipocyte
differentiation and mitochondrial function.
5
Lipodystrophy presents with fat loss on the face, buttocks, arms
and legs. There is also fat accumulation in certain areas. Patients
develop hepatic steatosis, central obesity, fat deposits in their
upper backs (interscapular fat pad) and increase in breast size.
Lipodystrophy does not progress, but usually does not reverse once
causative antiretroviral therapy has been stopped. Generalised
lipodystrophy is associated with severe insulin resistance and is
often accompanied by dyslipidaemia.
6
The metabolic syndrome has various definitions and criteria.
Essential components consist of diabetes or impaired glucose
tolerance, hypertension, dyslipidaemia (hypertrigyceridaemia and
low high-density lipoprotein cholesterol) and obesity–central obesity
(
increased waist:hip ratio or a body mass index > 30kg/m
2
).
Patients
on antiretroviral therapy are at high risk of developing the metabolic
syndrome and its complications.
7
Antiretroviral therapy is associated with diabetes and impaired
glucose tolerance, dyslipidaemia and lipodystrophy. Hence the
link between antiretroviral exposure and the metabolic syndrome
is not surprising. Other factors besides antiretroviral therapy that
predispose patients to diabetes and the metabolic syndrome should
be taken into consideration:
the age of the patient (> 50 years increases risk)
•
obesity, some contributing factors being sedentary lifestyle and
•
poor dietary habits
ethnicity: Asian and the black population are at increased risk
•
positive family history of diabetes, hypertension, dyslipidaemia.
•
4
Antiretroviral therapy involved in the development of
diabetes and the metabolic syndrome
Most commonly, the most marked effects are caused by nucleotide
reverse transcriptase inhibitors (NRTIs), especially stavudine, and
protease inhibitors. Protease inhibitors may cause fat redistribution,
hyperlipidaemia, insulin resistance and hyperglycaemia. They have
varying effects on glucose and lipid metabolism and need to be
assessed individually. The mechanisms of these metabolic changes
have not yet been fully clarified. There is likely to be a multifactorial
aetiology.
2
Lopinavir/ritonavir increases fasting triglyceride and free fatty
acid levels, but has little or no effect on insulin sensitivity. Indinavir
may induce insulin resistance by blocking insulin-mediated glucose
disposal by direct blockade of GLUT-4. However there is no effect
on lipid metabolism.
4, 5
Protease inhibitors are associated with reduced adiponectin
secretion and induced expression of interleukin 6. This may
contribute to the inhibition of insulin-stimulated glucose uptake.
9
Common drugs altering lipid profiles are stavudine, zidovudine,
efavirenz, lopinavir/ritonavir and earlier protease inhibitors. Drugs
with a cleaner lipid profile are lamivudine, emtricitabine, nevirapine,
tenofovir and atazanavir.
10
Management of diabetes in the HIV-positive patient
Making the diagnosis with SEMDSA guidelines. No screening
•
guidelines are in place for patients exposed to antiretroviral
therapy. Various factors need to be considered: risk factors,
choice of antiretroviral drug in a known diabetic patient, if and
when to switch antiretroviral therapy in a patient showing signs
of impaired glucose tolerance or insulin resistance.
4
Patient education at diagnosis is vital and regular ongoing
•
education is necessary. Thesepatients are already onantiretroviral
therapy and are trying to cope with HIV, antiretroviral therapy
and side effects. Adding more medication with further side
effects and more responsibility for another condition requires
