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Both the lack of a formal definition and uncertainty about the pathogenesis and possible long-term consequences, leads to a continuing discussion about appropriate guidelines for the assessment and management of HIV lipodystrophy syndrome and its metabolic abnormalities. Outside clinical studies, the diagnosis relies principally on the occurrence of apparent clinical signs and the patient reporting them. A standardized data collection form may assist in diagnosis (Grinspoon 2005). This appears sufficient for the routine clinical assessment, especially when the body habitus changes develop rather rapidly and severely. For clinical investigations however, especially in epidemiological and interventional studies, more reliable measurements are required. But so far, no technique has demonstrated sufficient sensitivity, specificity or predictive value to definitively diagnose the HIV lipodystrophy syndrome by comparison with results obtained from a "normal" population. A recent multicentre study to develop an objective and broadly applicable case definition proposes a model including age, sex, duration of HIV infection, HIV disease stage, waist-to-hip ratio, anion gap, serum HDL cholesterol, trunk to peripheral fat ratio, percentage leg fat, and intra-abdominal to extra-abdominal fat ratio. Using these parameters, the diagnosis of lipodystrophy had a 79 % sensitivity and 80 % specificity.

Although this model is largely for research and contains detailed body composition data, alternative models and scoring systems, incorporating only clinical and metabolic data, also gave reasonable results (for more information, see http://www.med.unsw.edu.au/nchecr).

Despite individual limitations, several techniques are suitable for measuring regional fat distribution. These include dual energy x-ray absorptiometry (DEXA), computer tomography (CT), magnetic resonance imaging (MRI) and sonography. Anthropometric measurements are safe, portable, cheap and much easier to perform than imaging techniques. Waist circumference alone, as well as sagittal diameter, are more sensitive and specific measures than waist-to-hip ratio. Repeated measurements of skin fold thickness can be useful for individual long-term monitoring but need to be performed by an experienced person.

The main imaging techniques (MRI, CT, DEXA) differentiate tissues on the basis of density. Single-slice measurements of the abdomen and extremities (subcutaneous adipose tissue = SAT, visceral adipose tissue = VAT) and more complex three-dimensional reconstructions have been used to calculate regional or total body fat. Limitations of these methods include most notably their expense, availability and radiation exposure (CT). Consequently, CT and MRI should only be considered in routine clinical practice for selected patients (e.g. extended dorso-cervical fat pads, differential diagnosis of non-benign processes and infections).

Table 1. HIV Lipodystrophy: Case definition and scoring system

Parameter

OR

95% CI

p value

Score*

Demographic

Gender

male

1.0

0

female

9.33

3.86-22.52

< 0.001

22

Age

<40

1.0

0

years

>40

2.02

1.20-3.4

0.008

7

years

Duration of HIV

< 4 years

1.0

0

infection

> 4 years

3.11

1.69-5.71

< 0.001

11

CDC Category

A

1.0

0

B

1.32

0.73-2.39

0.361

3

C

1.92

1.02-3.61

0.043

7

Clinic

Waist : hip ratio

0.1

1.34

1.06-1.69

0.014

multiply by 29

Metabolic

HDL cholesterol

0.1 mM

0.87

0.81-0.94

<0.001

multiply by -14

Anion gap

1 mM

1.10

1.04-1.166

0.001

multiply by 1

Body composition

VAT:SAT

< 0.45

1.0

0

0.45-

0.82

0.38-1.76

0.613

-2

0.83

0.83-

1.40

0.62-3.18

0.416

3

1.59

> 1.59

3.70

1.44-9.55

0.007

13

Trunk:

1.0

1.72

1.12-2.66

0.014

multiply by 5

limb fat ratio

leg fat ratio

> 21.4

1.0

-16

14.5-

1.27

0.57-2.87

0.559

-14

21.4

8.8-14.5

2.32

1.00-5.40

0.051

-8

< 8.8

5.04

1.90-13.35

0.001

0

According to Carr & Law (2003). This model has a sensitivity of 79% (95% CI, 70-85 %) and a specificity of 80% (95 % CI, 71-87 %).

* The final lipodystrophy score is obtained by adding individual scores for every variable and subtraction of 43 (constant). A final score of > 0 for a patient indicates the diagnosis of lipodystrophy, a score of < 0 means no lipodystrophy. CDC, U.S. Centers for Disease Control and Prevention; HDL, high-density lipoprotein; VAT, visceral adipose tissue; SAT, subcutaneous adipose tissue.

Table 2. Proposed grading scale for lipodystrophy based on lipodystrophy case definition cores relative to the subjective physician assessment-derived total lipodystrophy severity score (according to Carr & Law 2003).

Grading scale

Lipodystrophy-score

0

< 0

1

0-9.9

2

10-14.9

3

15-22.9

4

> 23

DEXA is appropriate for examining appendicular fat, which is comprised almost entirely of SAT, and has been successfully employed in epidemiological studies. However, SAT and VAT cannot be distinguished by DEXA, which therefore limits the evaluation of changes in truncal fat. Application of sonography to measure specific adipose compartments, including those in the face, requires experienced investigators and has been minimally applied in HIV infection so far. Bioelectrical impedance analysis estimates the whole body composition and cannot be recommended for measurement of abnormal fat distribution.

Patients should routinely be questioned and examined for cardiovascular risk factors, such as smoking, hypertension, adiposity, type 2 diabetes, and family history. For an accurate assessment of blood lipid levels, it is recommended to obtain blood after a fasting of at least 8 hours. Total cholesterol and triglycerides together with LDL and HDL cholesterol should be obtained prior to the initiation of, or switch to, a new potent antiretroviral therapy and repeated 3 to 6 months later. Fasting glucose should be assessed with at least a similar frequency. The oral glucose tolerance test (OGTT) is a reliable and accurate instrument for evaluating insulin resistance and glucose intolerance. An OGTT may be indicated in patients with suspected insulin resistance such as those with adipositas (BMI > 27 kg/m2), a history of gestational diabetes and a fasting glucose level of 110 to 126 mg/dl (impaired fasting glucose). An intravenous glucose tolerance test or hyperinsulinemic-euglycemic clamp appears only feasible in clinical studies. The diagnosis of diabetes is based on fasting glucose levels > 126 mg/dl, glucose levels of > 200 mg/dl independent of fasting status, or a 2-hour OGTT glucose level above 200 mg/dl. Additional factors that could lead to or assist in the development of hyperlipidemia and/or insulin resistance always need to be considered (e.g. alcohol consumption, thyroid dysfunction, liver and kidney disease, hypogonadism, concurrent medication such as steroids, preceptor blockers, thiazides, etc.).

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