HIV, Lipodystrophy and Your Quality of Life

This is a selection from an educational booklet published by HIV i-Base, a British treatment activist group, in July 2012. The full version of the booklet is available on their website, as well as in PDF format.

Table of Contents

Lipodystrophy and Metabolic Changes

Lipid = fat; dystrophy = disorder.

Lipodystrophy is a medical term referring to changes in body fat.

When this is part of a set of symptoms related to HIV treatment, it is usually linked to other metabolic changes.

The word 'metabolic' refers to how your body processes food into energy. This includes the production, regulation and storage of fats and sugars.

Although doctors are now aware of lipodystrophy as a side effect, you may still have to take an active role in getting the best monitoring and care.

The mechanism that causes fat loss is now understood. Hopefully, over the next few years, research will discover the cause(s) of metabolic fat gain.

What Are the Symptoms?

There are three broad sets of lipodystrophy symptoms:

  1. Fat loss (from legs and arms leaving veins more prominent, also from buttocks and the face).
  2. Fat gain (in the stomach, breasts in both women and men, shoulders, neck and sometimes small lumps of fat under the skin (called lipoma).
  3. Metabolic changes that increase the levels of fats and sugar in blood and intefere with the way your body produces and processes fat and sugar.

Any information about lipodystrophy needs to specify which of these symptoms are being discussed.

Each symptom is thought to have a different mechanism. You can have one symptom without the others.

Even when symptoms are generally linked to one class of drug, the effect of each drug can be very different.

Lipodystrophy is likely to be the result of several different factors rather than any single cause.

These include your HIV treatment history, individual drugs, lowest CD4 count, age, diet, exercise and family health.

These changes have been reported in men, women and children from a wide range of racial backgrounds.

How Many People Are Affected?

Many people are unlikely to notice any changes in body shape. Lipodystrophy occurs more rarely with current drugs compared to the earliest HIV meds.

The benefits from treatment still outweigh the risks. For most people any changes are likely to be mild. However, for a minority, problems are more serious.

Preventing lipodystophy is more important and more successful than trying to treat lipodystophy after it has developed.

As no one can predict who will be affected before starting treatment, careful monitoring is important. You use try switching to other HIV meds if you get symptoms with your first combination.

Monitoring Changes in Fat Distribution

There are several ways that changes in body fat distribution can be measured and monitored.

  • Most people are sensitive to physical changes in their body. This means that 'self-reporting', perhaps with careful measuring by a dietician, or photography can record any changes.
  • Some HIV clinics have access to scanning equipment, but unfortunately lipodystrophy is rarely monitored in this way. MRI and DEXA scans look at the breakdown within your body of fat and muscle. A test called BIA (Bio Impedance Analysis) are sometimes used. (See side box on Monitoring Tests).
  • Getting a DEXA scan, or well-lit photo, even if you only have slight changes, will give you a reference to know how quickly symptoms are progressing or improving. Some specialist clinics, including the lipodystrophy clinic at St Thomas' Hospital in London, provide baseline DEXA scans to all patients. You can self refer to this clinic.
  • As with your CD4 and viral load results, a single test result may only provide limited information. You are likely to need several tests over time to monitor changes.

If you are worried that you have lipodystrophy, make sure this is taken seriously. You should be offered monitoring and have any treatment choices explained.

Changing Treatment

Changing treatment can sometimes reverse fat loss.

Studies to reduce fat accumulation, have been less helpful.

Just because studies haven't shown a benefit, it doesn't mean that other treatments may not be better for you.

Whether you decide to change your treatment will depend on several things, including:

  • Your treatment history, and
  • How badly the lipodystrophy is affecting you.

If you change your combination, you have to change it to one that is just as effective against HIV.

Using combinations without nucleosides is one new strategy that is being studied. Another might be to use an entry inhibitor or integrase inhibitor instead of a PI or NNRTI.

Switching to drugs that have less impact on blood lipids can help with cholesterol and triglycerides.

It will be much easier to know if the switch has worked if you have been monitored before you make any change.

Even if this does not reverse the symptoms, changing to a different HIV drug may stop the symptoms getting worse.

Monitoring Tests

The following tests can monitor changes.

Having a measurement before starting treatment will make it easier to interpret any change.

Measurement

Careful measurement by a dietician using callipers can be useful if nothing else is available. This may be useful for fat increases but will be less sensitive for fat loss. Results may vary depending on the dietician. Measurement by callipers is not sensitive for small changes. Waist circumference (over 102 cm for men and 88 cm in women) and waist:hip ratio (higher than 0.95 in men and 0.90 in women) are also used.

DEXA (or DXA) scan (Dual X-ray Absorptiometry)

These scans are available at most main hospitals as they are routinely used for checking bone changes as people get older. You lay on a flatbed scanner for 5–20 minutes (depending on the scanner) for a full body scan. Your head is not scanned. The results provide a breakdown of your body composition into fat, bone and muscle. Some doctors would like a DEXA scan before any HIV treatment is started, and repeated annually to monitor for changes.

DEXA scans can show the percentage of body fat in each main section of your body -- in each arm, leg, your head and your trunk. An important limitation is that DEXA scans cannot show whether trunk fat is visceral (around the organs inside your abdomen) or subcutaneous (love handles -- under the skin but outside the abdomen). Visceral fat is most associated with HIV-related fat accumulation, and with increased health complications.

MRI scan (Magnetic Resonance Imaging)

These scans are much less readily available and the equipment required is more sophisticated and expensive. An MRI scan provides a computer image of the tissues, muscle and bone in a cross-section of any part of your body. An MRI scan can show how fat is distributed – whether it is subcutaneous (under the skin) or visceral (around your central organs) – and is very accurate at measuring any changes.

Bio-electrical Impedance Analysis (BIA)

BIA is a simple painless procedure that calculates the percentages of fat, muscle and water in the body according to height, weight, sex and age. It has mainly been used for HIV-related wasting but may also be useful in monitoring lipodystrophy.

Weight in people with lipodystrophy is generally stable. Fat redistribution (rather than weight gain or loss) is usually the issue. However, weighing yourself is important in case you have lost or gained weight without realising it.

Fat Loss (Lipoatrophy)

Associated drugs: d4T (stavudine), AZT (zidovudine, Retrovir), possibly efavirenz (Sustiva).

Symptoms

Lipoatrophy is the medical term for fat loss. Some researchers see this as the main symptom of HIV-related lipodystrophy.

Symptoms include loss of fat from under the skin on your arms and legs, which can make your veins look more prominent. It also includes loss from the face, especially sunken cheeks and temples.

Fat can be lost from the soles of the feet making walking more painful and tiring.

Role of d4T and AZT

Clinical lipoatrophy -- where you can see a change in body fat -- is common after using either d4T or AZT for more than six months. Both drugs affect the way that fat cells are produced and develop.

At a cellular level this can occur after only a few weeks or months of treatment.

Nucleosides (nukes) have been shown to damage the energy producing part of healthy cells called mitochondria.

In most studies, d4T damages fat cells at around twice the rate compared to AZT. d4T may also lead to lipoatrophy that is more difficult to reverse because it may damage cells at an earlier stage of their development.

Other Nukes?

Not all nukes cause lipoatrophy. This is not a side effect of 3TC, FTC, tenofovir and abacavir. The role of ddI is unclear.

The risk of lipoatrophy for people who are starting their first treatment should now be very low in Western countries.

Newer drugs do not cause this side effect, and increased monitoring should pick this up if you are using older drugs like AZT.

Neither d4T or AZT are recommended as routine first-line therapy in the UK, unless specific health complications require it. People currently using either of these drugs should be offered alternatives.

Other HIV Drugs and Fat Loss

Some studies reported a higher risk of fat loss when d4T or AZT were used with protease inhibitors.

The US study ACTG 5142 reported higher rates of fat loss in people using efavirenz compared to lopinavir/r, even when use of nucleosides were taken into account. These findings are not fully understood.

Several studies have reported higher rates of lipodystrophy in people using combinations that include three drug classes–nukes, NNRTIs and PIs.

Switching Treatment

Switching d4T or AZT to either abacavir or tenofovir, or using other combinations of drugs, can reverse the fat lost in limbs.

Reversing fat loss from the face or buttocks is more difficult, but this may be possible if you switch treatment early.

Switching is very safe, but the choice of new drugs needs to consider your previous treatment history to minimise the risk of drug resistance.

Any reversal of the fat loss is likely to take at least six months to become noticeable. This is because these symptoms developed slowly and if they are going to reverse this will also take time.

In studies where people switch, approximately +0.3 kg can be detected by scans at 6 months. In one study it took about two years (with an increase of +1.3 kg) before these patients noticed a difference.

Figure 3. Visual Scale to Grade HIV-Related Facial Lipoathrophy

Injectable Treatments

Many of these are used without approval for treating HIV-related fat loss.

Many substances have been used to treat HIV-related fat loss in the face but very few have been carefully researched.

Although non-permanent products need top-up treatment, these are currently the safest option. They work with your natural ageing process. Unlike permanent implants, there is no risk of it moving.

  • In the US, only New-Fill and Radiesse have been approved to treat HIV-related facial lipoatrophy.
  • In the UK, New-Fill is the most widely used, and as it is approved by some NHS trusts, we focus on this product in this guide. It is also supported by the strongest safety and efficacy results.

New-Fill (Sculptra)

New-Fill (polylactic acid, PLA) has shown promising results in correcting the effect of facial fat loss and is approved in the US as a treatment for HIV-related lipoatrophy. Most people require 4-5 sets of injections but severe cases may require more sessions.

New-Fill does not replace fat but generates new collagen growth. This gives the effect that your skin grows thicker, sometimes by up to 1cm. This process continues for several months after the injections have finished.

New-Fill has also been used to correct fat lost on the soles of the feet.

New-Fill is available free on the NHS in many of the larger HIV clinics in the UK. These include Brighton, Manchester, and any patient attending a London clinic. Since 2005, New-Fill has been available free on the NHS for any patient registered at a London clinic.

UK HIV treatment guidelines recommend that corrective treatment or surgery should be provided on the NHS.

However, New-Fill is not equally available throughout the UK. You may have to lobby you doctor and NHS trust. You may decide to register at a new HIV clinic to access this treatment.

Private treatment costs vary by clinic. Private treatment should ONLY be from a practitioner with experience treating HIV-related lipoatrophy.

Other Injectible Compounds

Radiesse

A second non-permanent filler approved in the US to treat HIV-related facial fat loss is called Radiesse. This is the trade name for a formulation of calcium hydroxylapatite suspended in a gel.

Although this is used in some private clinics in the UK, it is not approved by the London commissioners as a free NHS treatment.

Bio-Alcamid

Bio-Alcamid (polyalkylimide, Polymekon) is a ‘gore-tex’ filler that was used briefly but has now been linked to serious complications in 10% people. These relate to infections in the implant, often years after the procedure.

BioAlcamid no longer being used or recommended in many countries including the UK.

Although the manufacturer claims that BioAlcamid can be removed, it is a permanent implant because removal is traumatic and becomes increasingly difficult over time.

Anyone who has used BioAlcamid should inform their dentist about their implants and not have dental injections close to the implant site.

Other complications have been reported from trauma. Do not take up boxing or contact sports.

BioAlcamid has probably been used by several hundred people in the UK, and several thousand people in Europe and the US. Information is difficult to assess because this was largely in private clinics.

Silicone

Other approaches try to inject or implant material (fat or silicone) and hope it will stay in position. Very often, it disperses, moves or appears lumpy.

Silicone injections are dangerous and ineffective and were banned in the US many years ago.

A fine grade formulation called Silikon 1000 Microdroplets was studied in the US but further results were not available when updating this guide.

Fat transfer (Coleman technique)

Fat transfer involves extracting fat from one body site and reinjecting it surgically in another. This is usually subcutaneous fat from the stomach, which is then transplanted to the face.

Fat that has accumulated as a result of lipodystophy is not suitable for transplanting.

Although the results were very good the process is now less frequently used. This is because it is involves invasive, traumatic and expensive surgery.

Further info

A US community site with information on lipoatrophy treatment:

facialwasting.org

Fat Accumulation

Associated drugs: nukes, NNRTIs, protease inhibitors, possibly integrase inhibitors.

Symptoms

Fat accumulation can occur in the abdomen, breasts, neck and shoulders. It can occur in both men and women. Small bumps or collections of fat, called lipomas, can occur under the skin in other parts of the body including the pubis. A hard fatty lump in a mans breast is called gynaecomastia.

Abdominal fat can be visceral or subcutaneous. Visceral adipose tissue (VAT) is fat that is around the organs inside the abdomen. Subcutaneous adipose tisue (SAT) is fat under your skin ('love handles').

With visceral fat your stomach wall is pushed out from inside. Your stomach muscles can sometimes be quite defined, but your stomach will still be extended.

In severe cases, this can compress your internal organs and interfere with normal functions like breathing and eating. In these cases there is a greater medical urgency to reverse the fat accumulation. This may help you access treatments like growth hormone releasing factor (GHRF, tesamorelin), growth hormone (rHGH) or to switch to drugs like T-20 or raltegravir.

Treatments for Fat Accumulation

Many of the approaches used to lower cholesterol and triglycerides are being studied to treat fat accumulation. These include diet, exercise, and drugs in research.

Using more than one approach may be important. For example, using diet and exercise in addition to anthing else that you try.

Diet means having a healthy balanced diet. It does not mean you should dramtically cut calorie intake, which makes fat loss more difficult.

HIV-related fat accumulation seems to be due to your body signalling itself to produce more fat. Dietary fat is not the only mechanism, but high fat diets are unlikely to help. Whatever the cause, diet and exercise seem to be useful in helping reverse these changes.

Anabolic steroids are not recommended for fat accumulation as they are also likely to worsen fat loss.

Metformin can reduce central fat accumulation in people who already have insulin resistance but should not be used if you have a low BMI.

Recombinant Human Growth Hormone (rHGH) can reduce visceral abdominal fat and fat pads from the back of the neck and shoulders. Side effects, including the risk of insulin resistance and diabetes, are reduced using lower doses in more recent studies. Fat accumulation appears to return if rHGH is stopped.

A Growth Hormone Releasing Factor called tesamorelin (formerly TH-9507, tradename Egrifta) that can reduce visceral fat by 20% was approved in the US in 2010. It had less side effects than rHGH but there is no long-term data (maximum one year).

Tesamorelin is a continual treatment and fat returns if the treatment is stopped. A lower maintenance dose of tesamorelin has not been established.

Neither tesamorelin nor rHGH are approved in Europe as treatments for lipodystrophy. However, rHGH can be prescribed off-label on an individual patient basis. Tesamorelin is unlikely to be approved in Europe in the immediate future as the company withdrew the EU application in June 2012.

Neck, Shoulders, Breasts and Lipomas

Removing fat from the neck or shoulders using liposuction has worked well for some people. The results were sustained in 50% of people but fat returned after several months in 25-50% of people.

There may be a higher likelihood of a permanent result if at the same time, HIV treatment is modified and diet and exercise changed.

Unless the underlying metabolic mechanism is altered, fat accumulation may return after several months.

Liposuction cannot be used for visceral fat accumulation in the abdomen.

Anecdotally, testosterone cream massaged onto the fat pads reduced fat pads on the shoulders. A lower dose should be used for women than for men.

Liposuction and surgery are also used to reduce breast size in both men and women.
Breast lumps (gynaecomastia) in men has been mainly linked to efavirenz, so switching treatment is a first option.

Dihydrotestosterone gel (Andractim) may help. Women with lipodystrophy may have higher levels of testosterone than either HIV positive women without lipodystrophy or HIV negative women. It is not clear whether this is due to high insulin levels associated with lipodystrophy, although a link between the length of time on PI-therapy (but not other drugs) and a greater chance of higher testosterone was found in one study.

Switching HIV Drugs

Studies switching individual drugs have been less helpful with fat accumulation than with fat loss. In theory, if one particular drug is linked to these body changes then it is very reasonable to at least try another one, in case this works for you.

If you change your combination, you have to change it to one that is just as effective against HIV.

Switching from efavirenz can reduce gynaecomastia in men.

There have been anecdotal reports and case studies of people whose shoulder and/or abdominal fat decreased after switching to atazanavir. A general benefit was not seen in a larger study.

Fat accumulation does not seem closely related to high blood lipids. So far, newer drugs that affect lipids less (unboosted atazanavir, nevirapine, raltegravir and T-20, maraviroc) have not shown reduced rates of fat accumulation.

Figure 4: Illustration of MRI scans
Figure 4: Illustration of MRI scans An MRI scan through your stomach shows that fat is inside the abdomen and around the organs rather than being directly under your skin. Key: subcutaneous fat shows as light yellow and visceral fat as olive yellow.

Cholesterol and Triglycerides

**Cholesterol and triglycerides are two types of fats (lipids) that are carried (and can be measured) in blood.
**

These fats perform essential functions, including making effective cell structures and processing vitamins A, D, E and K.

Cholesterol and trigylcerides are often referred to as ‘lipids’.

When levels are too high, this increases the risk of heart disease and stroke in the general population.

However, if this is a side effect of treatment for a short time, there may be differences to the general population where abnormal lipids are often increased and sustained for many years or decades.

HIV and Lipids

HIV itself (before treatment) reduces both good and bad cholesterol and triglycerides are higher. Starting treatment with any combination will reverse these lipid effects as part of a return-to-health effect.

Because many HIV drugs and lifestyle factors affect lipids this is complex to interpet.

Testing and Monitoring

Cholesterol and triglycerides should be checked when you are first diagnosed. They should also be checked before starting or changing treatment and then three months after any change.

Routine monitoring for someone on stable treatment should then involve testing lipids every 6-12 months.

Most clinics will do this at the same time as your CD4 and viral load, but you may need to ask whether this is being done. These tests are best done fasted (on an empty stomach) so don't eat or drink anything before your have your blood taken on those days.

Management of lipid levels should be part of an assessment of your risk for heart disease. This is also related to other risk factors, including lifestyle factors.

Lipids are first managed by diet and exercise, then by switching HIV treatment and then by using lipid lowering drugs.

Cholesterol

Total cholesterol (TC) is measured first. If these results are high then a further test will break this down into two different types of cholesterol:

  1. High Density Lipoprotein (HDL) is 'good' cholesterol. It removes fats from your arteries.
  2. Low Density Lipoprotein (LDL) is 'bad' cholesterol. It is a small molecule that carries fats from the liver to other parts of your body and can lead to heart disease.

Target levels for total and LDL cholesterol and desirable levels for HDL cholesterol and triglycerides are shown in Table 5. Target levels are lower for people who already have high cardiovascular risk due to other factors. Each reduction in LDL by 1.0 reduces the risk of cardiovascular mortality by 20%.

The TC:HDL ratio is used to determine the importance of using lipid lowering drugs, but is not used for monitoring afterwards.

Table 5: Target/Desirable Levels for Fasted Lipids (EACS Guidelines)
Total cholesterol (TC)Less than 5.0 mmol/L (under 4.0 if high risk)
LDL cholesterolLess than 3.0 mmol/L (under 2.0 if high risk)
HDL cholesterolHigher than 0.9 mmol/L
TriglyceridesLess than 1.7 mmol/
Table 6: Factors That Can Affect Cholesterol and Triglycerides
HIVTC is lower and TG is higher before HIV treatment
HIV treatmentSome drugs affect cholesterol (LDL and HDL) and TG
AgeingAgeing can increase cholesterol and TG
SmokingSmoking increases LDL. Quitting increases HDL and reduces TG
DietDiet affects blood lipids
ExerciseExercise has a good impact on lipids
Other infectionsOther health conditions can affect lipids.

Key: TC = total cholesterol; TG = triglycerides; HDL = high density lipoprotein ("good cholesterol"); LDL = low density lipoprotein ("bad cholesterol"); TC:HDL ratio is often more important than individual levels, with a target of 4.5 or less. Note: HDL are large particles that can pick up LDL to be broken down and eliminated from your body. LDL are small particles that have a higher risk of getting stuck and causing a blockage.

Triglycerides

Some guidelines see triglycerides (TG) as an independent risk factor for heart disease. Others state that the evidence for treating moderate triglycerides is less strong.

In the D:A:D study, most of the impact of high triglycerides was explained by other risk factors, but this still remained at +10% per year.

Although there is a lot of individual variability, target fasted levels of under 2.2 mmol/L are considered normal and of 2.2-4.4 mmol/L are borderline. Above this, the risk of heart disease increases.

Levels above 10 mmol/L are very high and need urgent treatment due to the increased the risk of pancreatitis.

Although less that 1.7 mmol/L is a target, treatment would not usually be used unless levels are over 2.3 mmol/L.

Changing HIV Drugs in Your Combination

Lipids generally improve after switching away from HIV drugs that have caused this change.

This usually involves switching from a protease inhibitor (PI) to nevirapine, raltegravir or to another PI that affects lipids less (atazanavir/r or darunavir/r). Tenofovir has a slighter better lipid impact compared to abacavir.

Nevirapine may help by increasing HDL (good cholesterol). The boosting dose of ritonavir to some extent reduces the benefits of protease inhibitors with better lipids profiles.

The debate on the impact of different strategies on reducing risk for heart disease is likely to develop and change over the next few years.

The choice of switch drugs will depend on your previous treatment history and previous history of resistance.

Treatment and Management

Options to improve lipids include lifestyle changes (diet etc), switching HIV meds and using lipid lowering drugs.

Cholesterol and triglyceride levels can often be improved by diet changes (especially reducing saturated fat, trans fat, cholesterol and alcohol and increasing fibre) and by starting or increasing exercise.

Weight loss, if you are overweight, will have a positive impact on lipids too.

Omega-3 can reduce triglyceride levels. Taking a supplement may be more effective that just changing diet. For example, a 4 gram (g) daily dose Omacor, (90% omega-3 acid ethyl esters) is equivalent to 150 g mackerel or 700 g tuna or 1.1 kg cod or 280 g salmon or 1.7 kg eel or 850 g shrimps.

Lifestyle targets for the general population for people at risk of heart disease or diabetes are listed in Table 7.

Table 7: Lifestyle Targets to Reduce Risk of Heart Disease (From the UK Guidelines)
1Do not smoke
2Maintain ideal body weight for adults (body mass index 20- 25 kg/m2) and avoid central obesity (waist circumference in white caucasians less than 102 cm in men and less than 88 cm in women (for Asian/Oriental people this is less than 90 cm in men and less than 80 cm in women)
3Keep total dietary intake of fat to (30% of total energy intake)
4Keep the intake of saturated fats to (10% of total fat intake)
5Keep the intake of dietary cholesterol to less than 300 mg/day
6Replace saturated fats by an increased intake of monounsaturated fats
7Increase the intake of fresh fruit and vegetables to at least five portions per day
8Regular intake of fish and other sources of omega 3 fatty acids (at least two servings of fish per week)
9Limit alcohol intake to less than 21 units/week for men or less than 14 units/ week for women
10Limit the intake of salt to less than 100 mmol/l day (less than 6 g of sodium chloride or less than 2.4 g of sodium per day)
11Regular aerobic physical activity of at least 30 mins per day, most days of the week, should be taken (for example, fast walking/ swimming)

Source: JSB2 guidelines, 2003

Lipids generally improve after switching away from HIV drugs that cause this side effect.

If diet, supplements, exercise and switching treatment (if appropriate) are not enough, then lipid-lowering drugs are generally more effective. They are widely used and have a low risk of side effects. Fibrates reduce triglycerides and increase HDL cholesterol and statins reduce LDL cholesterol.

Lipid-lowering drugs need to be prescribed by an HIV-specialist as they can interact with HIV drugs. For example some statins should never be used and some require increased or decreased dosing when used with PIs or NNRTIs.

Studies are also looking at metformin (an insulin sensitising drug), rosiglitazone and growth hormone.

A study of HIV positive men looking at the effects of exercise and testosterone found that testosterone significantly reduced levels of ‘good’ cholesterol (HDL). This is a concern for people with lipodystrophy who already have elevated triglycerides and ‘bad’ cholesterol (LDL).

Although muscle gain and fat loss were greater in the testosterone group, levels of good cholesterol increased in people who used exercise without testosterone, and this may be more appropriate for people with lipodystrophy.

Although anabolic steroids can increase muscle mass they can also reduce fat, and have the potential to worsen lipoatrophy and lipid levels.

Further information

European AIDS Clinical Society (EACS) metabolic guidelines

ESC/EAS Guidelines for the management of dyslipidaemias (Eur Heart Jour, 2011)

Increased Blood-Sugar Levels and Risk of Type 2 Diabetes

Associated drugs: some protease inhibitors and some nukes

Glucose and Insulin

Glucose is a type of sugar. Your body relies on glucose to provide energy. A hormone called insulin processes the sugar and allows it to enter cells.

Insulin also regulates production of new glucose by the liver, levels of glucose in the blood, and metabolic aspects of fat cells.

Insulin resistance is the term for when this system fails to work properly. Although your body produces more insulin to compensate, if insulin resistance continues, and sugar levels remain high, you can develop diabetes.

Insulin levels are difficult to measure, but glucose levels, usually checked by fasting or non-fasting blood tests, are routinely used for monitoring risk.

Types of Diabetes

Type-2 diabetes mellitus (T2DM) is an adult illness that usually develops slowly. It can take years or decades for mild insulin resistance to progress to diabetes, but the impact on the risk of heart disease is serious.

Some protease inhibitors can increase glucose levels and the risk of Type-2 diabetes.

Type-2 diabetes is different from Type-1, which is caused by low insulin production, often in childhood, and which is managed by insulin injections.

Risk of Long-Term Health Problems

High untreated blood-sugar is related to many long-term health problems. This can include the kidneys, nerves, eyes and vision, risk of heart disease and stroke, erectile dysfunction in men and pregnancy complications in women.

Diabetes can increase the risk of having a heart attack as much as smoking.

Fat and sugar metabolism are also closely linked and insulin resistance is a complication of HIV therapy that is getting more focus. It is directly related to some protease inhibitors and possibly indirectly related to older nukes through their effect on fat distribution. Changes in blood glucose levels and insulin sensitivity are closely related to other symptoms of lipodystrophy.

What Can Help

As with HIV-negative people, mild insulin resistance can be managed by diet, exercise and stopping smoking. Switching HIV drugs associated with increases in blood-glucose is recommended when appropriate.

Dietary advice involves reducing processed sugars, refined and fast foods, white flour and potatoes as they all cause quick sugar 'highs'. Complex carbohydrates (wholemeal bread, wholemeal and al-dente pasta, porridge, most vegetables) provide energy more slowly with less impact on sugar levels.

Metformin may help people with insulin resistance and fat accumulation. Pioglitazone may help people with insulin resistance and fat loss. Drug interactions with HIV drugs (PIs and NNRTIs) means that drug-level monitoring (TDM) should be used to confirm dosing.

Symptoms of High Blood-Sugar, and Diabetes

  • Feeling thirsty or excessively hungry
  • Feeling tired
  • Low concentration
  • Blurred vision
  • Unexplained weight loss
  • Frequent need to urinate
  • Slow healing of cuts
  • Tingling in hands or feet (neuropathy)
  • Nausea and vomiting

Risk Factors for Abnormal Glucose

  • Liver damage or coinfection with hepatitis C
  • Family history of diabetes
  • Overweight (BMI higher than 30)
  • Lipodystrophy or lipoatrophy
  • Low exercise
  • Age over 40
  • High blood pressure (over 130/85 but this depends on age and other risk for heart disease)
  • High cholesterol and triglycerides (over 1.7 mmol/L) and low HDL (good) cholesterol (less than 0.9 mmol/L)
  • History of insulin resistance or high glucose
  • Other meds, including niacin, glucocorticoids, megestrol and Growth Hormone and some PIs

Tests to Diagnose and Monitor Glucose and Insulin Levels

Fasting glucose test

Measures blood sugar after an 8-hour fast. This should be measured before starting and after switching treatment, and at least annually after this.

Fasting levels over 5.6 mmol/L in plasma indicate insulin resistance, and the need for an oral glucose tolerance test (OGTT).

Random glucose test

Unfasted glucose levels are less accurate but are taken shortly after someone has had something to eat or drink. If it is greater than 5.17 mmol/L other tests are run. Diabetes is over 11.1 mmol/L.

Oral glucose tolerance test (OGTT)

Monitors levels of glucose every 30-60 minutes for two hours after fasting for 8-hours and then drinking a measured glucose drink. Healthy glucose on this test should be less than 3.62 mmol/L. If it is greater than 5.17 mmol/L other tests are run. Diabetes is over 11.1 mmol/L.

Haemoglobin A1c

This tests how much glucose adheres to red blood cells. It is used to determine average glucose levels over several months. Normal range for someone without diabetes is 4-6% and managed treatment for someone with diabetes should aim to keep this under 7%.

Fasting insulin test -- and results used to calculate HOMA-IR score (Homeostatic: Model Assessment-Insulin Resistance).

Measuring glucose is generally preferred to measuring insulin directly.

Insulin tolerance test (also called glycemic clamp)

This is where insulin is infused by intravenous line, and glucose given until normal blood sugar levels are reached. This is expensive and again is rarely used.

Further information

European AIDS Clinical Society (EACS) metabolic guidelines