Some people with
HIV have a higher risk of developing Type 2 diabetes. Robert Fieldhouse
finds out why and what can be done
Illustration: C(Aitch)
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Living
with one long-term medical condition is quite enough for most of us. Yet as
we live longer with HIV, many of us face competing health concerns, including
diabetes. To mark national diabetes awareness week (11 to 17 June) PN has
turned the spotlight on how this common but sometimes complicated condition
affects people living
with HIV.
The available evidence on diabetes and HIV makes uncomfortable reading. Men
with HIV on HAART are more than four times more likely to develop new onset
diabetes than HIV negative men. And HIV positive women on a protease inhibitor
(PI) are three times more likely to develop diabetes than women on other drugs
and HIV negative women. If that wasn’t enough to worry about, having
a CD4 count below 300 at some point also appears linked to the development
of the condition.
Several studies show diabetes may be associated with HIV infection itself
and that its incidence may increase with longer exposure to treatment. But
it may be that diabetes occurs less frequently now than in the early HAART
era when there was more protease inhibitor prescribing.
Diabetes occurs if our body fails to produce enough, or respond to, the hormone
insulin. This affects the amount of glucose in our blood. As we age and gain
weight we are all more likely to develop diabetes, so everyone, regardless
of HIV status, should be regularly screened for hyperglycaemia (high blood
sugar). This is when too much glucose circulates in the blood. A measurement
of over 11mmol/l (or 7mmol/l while fasting) is usually considered a diagnosis
of hyperglycaemia and therefore diabetes.
Diabetes: the two main types
• Type 1 Often diagnosed in childhood, it’s caused by the body’s
failure to produce enough insulin, preventing cells from using glucose properly.
• Type 2 Also known as ‘mature, new onset diabetes’ or ‘insulin
resistance’, it’s caused by the body failing to respond to insulin.
It’s more common than Type 1 and can be caused by being overweight and
a lack of exercise. It develops as we get older and may also occur due to
using HIV drugs, particularly PIs.
How does diabetes develop?
Our cells need glucose for energy. Over time, they 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’ as they require more
insulin to maintain glucose levels within the normal range. As insulin resistance
increases, our fat cells release fatty acids to supply our livers with more
raw materials to make glucose, but this fails to restore normal glucose levels.
Eventually glucose levels rise to a point where they trigger physical symptoms
of hyperglycaemia such as tiredness, frequent urination, constant thirst due
to loss of fluid, blurred vision and weight loss. In Type 2 diabetes, more
serious problems can arise such as lesions in the retina of the eye, kidney
disorders, nerve damage (especially in the legs), impotence, bacterial or
fungal skin infections and heart disease (angina, stroke or heart attack).
HIV drugs and Type 2 diabetes
Studies suggest between two and 10 per cent of people taking HIV meds develop
Type 2 diabetes and the prevalence may be growing as people spend longer on
treatment. In the D:A:D study of 25,000 people living with HIV, researchers
found PI use was associated with a six per cent increase in diabetes for each
year on that class of drug.
If you are on therapy you should have your glucose levels monitored regularly
so steps can be taken to reduce rising glucose levels before diabetes develops.
Type 2 diabetes may emerge rapidly after beginning a new drug combo. There
are some reports of people with slightly elevated glucose levels advancing
to a diabetic state in just a matter of weeks. Extra weight around our middles
predisposes us to Type 2 diabetes because fat surrounding organs is highly
insulin resistant.
Increased heart disease risk
Developing diabetes may put us at greater risk of heart disease in future.
When large amounts of glucose are present in our blood, the sugar becomes
attached to low-density lipoprotein (LDL) or ‘bad’ cholesterol.
This causes cholesterol to be oxidised more easily. It’s taken up into
the wall of blood vessels where it forms plaques that contribute to hardening
of the arteries and heart disease.
When sugar attaches to high density lipoprotein (HDL) or ‘good’
cholesterol, the liver finds it less easy to remove this cholesterol from
the bloodstream. High glucose levels also increase blood clotting and reduce
the flexibility of blood vessels. These factors contribute to heart problems.
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Hep
C coinfection
Being coinfected with hepatitis C appears to further increase our risk of
developing diabetes and hyperglycaemia, especially for those of us over 40
or with a previous history of pancreatitis.
Obesity
Being severely overweight is a major factor in HIV negative people developing
Type 2 diabetes. A recent study found obesity was an increasingly important
complication of HIV, with women and black people more likely to suffer from
both.
Fitness factors
We can help to normalise glucose levels by increasing the amount of daily
exercise we do. Ideally we should try to raise our heart rate above normal
levels for at least 20 minutes each day. Brisk walking, swimming, cycling,
jogging or aerobics are good for this.
Fat factors
People with diabetes should also eat more fibre, choosing wholegrains, beans,
and fresh fruit and vegetables and cutting back on saturated fats (butter,
lard, cream), trans- fatty acids (margarine) and hydrogenated fats (in prepared
foods such as cakes, biscuits and pizza).
We should also eat more polyunsaturated fats like cornflower, sunflower or
safflower oil and soya beans. You should consult a dietitian with specialist
knowledge of HIV before you start a diet designed to deal with diabetes.
Drug treatments for Type 2 diabetes
If dietary and exercise changes are insufficient to bring your glucose levels
back to normal, and you have limited antiretroviral options to switch to,
you may need additional drugs to treat diabetes. People starting drugs for
diabetes should continue to exercise and stick with dietary changes, to help
lower blood sugar.
Drug therapy for diabetes aims to lower the peak in our glucose levels after
we eat, since a rise in glucose levels after eating plays an important role
in stimulating insulin resistance and developing complications such as retinal,
nerve or kidney damage.
First-line diabetes treatment
First-line treatment comes from a class of anti-hyperglycaemic drugs called
sulphonylureas. These include glipizide (Glibenese) and glimepiride (Amaryl).
They stimulate the pancreas, a small organ near the liver, to produce more
insulin. These drugs can cause weight gain of up to 5kg and blood sugar to
fall very low, which may lead to a state of hypoglycaemia (low blood sugar).
Glyburide is not recommended for use in people with kidney abnormalities,
and is also associated with a higher risk of hypoglycaemia.
Other alternatives
An alternative option is metformin (Glucophage), which does not act directly
on insulin, but rather cuts glucose production in the liver. Metformin tends
to reduce weight, unlike the sulphonylureas, and reduce insulin levels. It’s
commonly used in obese patients, but may be less suitable for people who have
already lost a significant amount of body fat due to HIV drugs.
Metformin may also reduce triglyceride and LDL ‘bad’ cholesterol
levels, which are often elevated in people with high glucose levels on combination
therapy. One study showed that metformin and exercise helped cut risk of heart
disease and improved body fat redistribution in people with HIV who have taken
HAART.
Its most common side effects are stomach pain, nausea and diarrhoea, reported
by up to half of all people during the first few weeks of treatment. Diarrhoea
and gastrointestinal problems occur less frequently if metformin is taken
with food.
Glitazones
A third class of drugs is the thiazolidinediones, often referred to as glitazones.
These increase insulin-stimulated uptake of glucose by muscle cells. Rosiglitazone
(Avandia) and pioglitazone (Actos), have shown the same ability to control
insulin as metformin and sulphonylureas. The drugs can improve HDL ‘good’
cholesterol levels and reduce triglyceride levels, blood pressure and blood
clotting. No long-term studies have yet reported on their impact on the risk
of heart disease.
Glitazones are associated with weight gain, an effect that may not be entirely
unwelcome in people with lipodystrophy, because they reduce visceral fat deposits
and increase levels of subcutaneous fat, which often decline after extended
use of nukes.
But there is conflicting evidence about this effect on fat distribution in
people with HIV-related body fat changes. Two studies showed no improvement
in subcutaneous fat levels or body weight, while another found subcutaneous
fat increased in people treated with rosiglitazone for three months. Why different
studies have drawn different conclusions is unknown. One worry is that rosiglitazone
in people with HIV boosts blood levels of triglycerides and cholesterol. Elevated
lipids are a risk factor for heart disease and stroke. So we don’t know
the long-term consequences of their use by people with HIV.
Oral therapy
Therapy may also include insulin injections, or a combination of oral tablets
to normalise glucose levels. Insulin therapy is usually reserved for severe
cases of Type 2 diabetes, although some experts believe that if it could be
used earlier, remission of Type 2 diabetes might be achieved more frequently.
A question of age
As we live longer with HIV, it’s natural we may have to deal with other
age-related health problems. This makes staying healthy through diet, exercise
and choosing drug therapy even more important. If you are
concerned that you are at risk of developing diabetes, discuss your concerns
with your healthcare team.
• www.diabetes.org.uk
