Clinical Evaluation


Classification

BMI (kg/m2) cut-off points

Comorbidity risk

Underweight

<18.5


Normal range

18.5–24.9

Normal

Pre-obese

25.0–29.9

Increased

Obese class I

30.0–34.9

Moderate

Obese class II

35.0–39.9

High

Obese class III

≥40.0

Very high


Source: Adapted from WHO [1]



The use of BMI as a proxy for adiposity, the true determinant of the obese state, has been criticised, given that body weight is the sum of individual organs and tissues and therefore it includes adipose tissue, skeletal muscle mass and organs mass. On a population level, a strong positive correlation between BMI and overall body fat content has been reported [3]. However, at an individual level, a substantial variation in percentage body fat may be observed for any given BMI value [4]. Therefore, a high BMI may correspond to a low fat-free mass and a substantial fat accumulation in an obese patient, or to a large skeletal muscle mass and normal fat mass in a healthy athlete, in which high BMI simply reflects increased muscle mass, which has nothing to do with obesity and associated diseases. Visual inspection is usually sufficient to discriminate these extremes in body composition, but in some subjects the distinction may be more subtle, and a more precise determination of body composition may be requested. Fat mass and fat-free mass may be reliably distinguished and measured by direct densitometric methods (underwater weighing; total body densitometry). Dual-energy X-ray absorptiometry (DEXA) has a good reproducibility for total body fat mass (coefficient of variation: 2–3 %) and total body fat-free mass or lean soft tissue (1–2 %), and it is sensitive in assessing minimal changes in body composition [5]. Unfortunately, DEXA is not applicable in routine office practice; it is costly and exposes patients to a low dose of radiations. Bioelectrical impedance analysis (BIA) is an indirect method that derives body composition values from electrical data (reactance, resistance, impedance) measured during the passage of a small electrical current through the patient’s body [6]. The method is applicable also in the outpatient setting and does not have virtually potential side effects, and it is relatively not expensive. However, the reliability of BIA in the accurate determination of fat mass and fat-free mass may be questioned. BIA measurements must be standardised in order to obtain reproducible results (reported mean coefficients of variation for within-day measurements: 1–2 %), and overall reproducibility/precision is estimated around 2.7–4.0 %, with prediction errors for FFM ranging from 3 % to 8 % [7]. These large errors may be even larger in obese patients and limit the utility of BMI in clinical evaluation.

A further important limitation for BMI is that this index does not convey any information on fat distribution (e.g. visceral fat accumulation and fatty infiltrations in individual organs) that is considered now an important determinant of metabolic and cardiovascular risk [8]. A clear evidence in favour of the inclusion of fat distribution in the clinical evaluation comes from the observation of normal-weight or slightly overweight subjects with low subcutaneous but increased visceral fat mass. This TOFI (thin-on-the-outside fat-on-the-inside) sub-phenotype has been observed in both male and female subjects and increases an individual’s risk of metabolic disease [4]. The elevated visceral fat found in individuals classified as TOFI is accompanied by increased levels of ectopic fat deposition both in the liver and in the skeletal muscle. Lipid accumulation in non-adipose cells (ectopic fat) may impair the normal function of some tissues through a process known as “lipotoxicity”. Ectopic storage of excess lipids in organs such as the liver, skeletal muscle, and pancreatic beta cells may be the causative link between fat distribution and the metabolic syndrome or cardiovascular diseases [9]. Similar findings have been already reported in obese individuals, where obese subjects with a disproportionate accumulation of visceral fat had increased incidence of metabolic disorders and cardiovascular events [10].

Visceral fat accumulation may be measured precisely with CT and MRI, but it may be difficult to quantify at a clinical level, and surrogate anthropometric indexes have been proposed. In particular, the waist circumference has been selected as a reliable clinical indicator of visceral fat accumulation, and having a large waist is associated to a higher prevalence of metabolic disorders and cardiovascular diseases [11]. Therefore, the measurement of the waist circumference is suggested for the determination of cardiovascular risk of overweight and obese patients, and the integration of BMI and waist values may be used to better stratify their health risk [11] (Table 15.2). Waist circumference should be measured with a plastic stretch-resistant tape on the subject in the standing position, at the end of a gentle expiration, without constricting the abdomen. Different anatomic landmarks have been suggested for waist measurement [12]. According to WHO guidelines, waist circumference should be measured at the approximate midpoint between the lower margin of the last palpable rib and the top of the iliac crest [13]. The US National Institutes of Health (NIH), by applying the same method used for the US National Health and Nutrition Examination Survey (NHANES) III, indicates that waist circumference measurement should be made at the top of the iliac crest [11]. The two methods did not produce the same results, with the WHO method underestimating waist values in respect to the NIH method, particularly in women [12]. It should be emphasised that the cut-off values proposed for “at-risk” waist values (Table 15.2) and utilised for the original ATP-III definition of the metabolic syndrome are those proposed by the NIH. The simple measurement of waist circumference has replaced the use of the waist-to-hip circumference ratio (WHR), originally proposed as a powerful marker of fat distribution. More recently, on the basis of several epidemiological studies showing that having a large hip circumference may confer some BMI-independent protection from metabolic and cardiovascular diseases, particularly in women, a return to the measurement of hip circumference has been proposed [14]. The reliability of waist circumference in assessing visceral fat accumulation may be reduced in obese women, particularly at higher BMI levels [15]. Other anthropometric indexes have been therefore suggested as more effective than waist circumference for the prediction of visceral fat depots, with the sagittal abdominal diameter (SAD) being the more promising one [16]. SAD is determined at the highest point of the abdominal surface with the subject in the supine position and during normal breathing by means of a specifically made instrument. Abdominal ultrasonography is another reliable, repeatable and less expensive method which has been proposed to detect visceral fat deposition without radiation exposure [17]. Peritoneal fat thickness is considered the gold standard echographic index for visceral fat prediction in abdominal ultrasonography, and it corresponds to the distance from the internal face of the recto-abdominal muscle and the anterior wall of the aorta, measured with the echographic probe transversely placed perpendicular to the skin in the midline of the abdomen [17]. The increasing availability of portable low-cost ultrasonographic instruments will probably stimulate the applicability of ultrasonographic measurements of visceral fat accumulation in clinical practice.


Table 15.2
Classification of overweight and obesity by BMI, waist circumference and associated disease risk


















































   
Disease risk relative to normal

BMI

Obesity class

Men waist <102 cm

Men waist >102 cm

Women waist <88 cm

Women waist >88 cm

<18.5

Underweight



18.5–24.9

Normal range



25.0–29.9

Overweight

Increased

High

30.0–34.9

Obese class I

High

Very high

35.0–39.9

Obese class II

Very high

Extremely high

≥40.0

Obese class III

Extremely high

Extremely high


Source: Adapted from NIH [11]

The presence of ectopic fat deposition in the relevant organs may be even more difficult to quantify than visceral fat accumulation in clinical practice. However, liver fat infiltration (hepatic steatosis) may be roughly, albeit imprecisely, estimated by ultrasound [18]. An alternative approach to the quantification of ectopic fat accumulation may be represented by the ultrasonographic measurement of epicardial fat, which has been suggested as a further marker of metabolic and cardiovascular risk [19].



15.3 Metabolic Status and Cardiovascular Risk


Several epidemiologic studies confirmed the strict relationships between BMI and type 2 diabetes, and 65–75 % of the cases of type 2 diabetes may be attributed to the presence of overweight and obesity [1]. According to American Diabetes Association’s (ADA) Standards of Medical Care, adults of any age who are overweight or obese and who have one or more additional risk factors for diabetes should be tested to detect type 2 diabetes and prediabetes [20]. Additional risk factors for diabetes include physical inactivity, first-degree relative with diabetes, high-risk ethnicity, previous delivery of a macrosomic baby or previous gestational diabetes, hypertension, low HDL cholesterol level, hypertriglyceridaemia, polycystic ovarian syndrome in women, other clinical conditions associated with insulin resistance (e.g. severe obesity, acanthosis nigricans), and history of cardiovascular disease [20]. The glycosylated haemoglobin (A1C), the fasting plasma glucose (FPG) or a 2-h 75-g oral glucose tolerance test (OGTT) are all considered appropriate for testing [20]. However, the three tests do not necessarily detect diabetes in the same individuals. In particular, many obese patients may have normal FPG, but abnormal post-load glucose levels. More frequent retesting should be considered in patients testing positive for prediabetes in previous occasions. The diagnostic criteria for diabetes and prediabetes are summarised in Table 15.3. In case of diabetes, a complete screening for macro- and microvascular complications should be scheduled [20].


Table 15.3
Criteria for the diagnosis of diabetes and prediabetes in adults




























Method

Diabetes

Prediabetes

FPG

FPG > 126 mg/dL (7.0 mmol/L)

FPG 100–125 mg/dL (5.6–6.9 mmol/L) (impaired fasting glucose or IFG)

2-h PG during OGTT

2-h PG >200 mg/dL (11.1 mmol/L)

2-h PG 140–199 mg/dL (7.8–11.0 mmol/L) (impaired glucose tolerance or IGT)

A1C

A1C > 6.5 %

A1C 5.7–6.4 %

Random PG

Random PG > 200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycaemia or hyperglycaemic crisis



Source: Adapted from ADA [20]

FPG fasting plasma glucose defined as no caloric intake for at least 8 h. OGTT oral glucose tolerance test performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. A1C, glycosylated haemoglobin performed in a laboratory using certified and standardised assay

The association between arterial hypertension and obesity is very well documented. The prevalence of hypertension in adults with obesity is three to five times higher than in normal-weight subjects [1]. Arterial hypertension in obese patients is frequently unrecognised or suboptimally treated. The office measurement of systolic and diastolic blood pressure with a sphygmomanometer with a normal cuff size can grossly overestimate blood pressure levels in obese patients. The use of an appropriate cuff size is therefore of paramount importance in obese patients. In practice, a large adult size 16 × 36 cm should be used for arm circumferences ≥35 cm and an adult thigh size 16 × 42 cm for arm circumferences ≥45 cm [21]. Diagnostic criteria for arterial hypertension in overweight and obese patients did not differ from those used in the general population, and hypertension may be therefore defined as a systolic blood pressure ≥140 mmHg, or a diastolic blood pressure ≥90 mmHg or the use of any anti-hypertensive drug [22].

Obese patients, in particular in the presence of abdominal obesity or visceral fat accumulation, are frequently characterised by a particular dyslipidaemia with high triglycerides and low HDL cholesterol levels. LDL cholesterol levels are usually not particularly affected, but there is an increase in the proportion of a particular class of small dense LDL particles [1] that are considered highly atherogenic. Small dense LDL are not measured in normal clinical practice, but their presence may be indirectly estimated trough the measurement of apo-B lipoprotein and the ratio between apo-B lipoprotein and LDL cholesterol [1]. An alternative and more simple way to assess atherogenic dyslipidaemia in patients with abdominal obesity is the calculation of the non-HDL-cholesterol levels (total cholesterol minus HDL cholesterol). Non-HDL cholesterol may be used as an estimation of the total number of atherogenic particles in plasma [VLDL + intermediate-density lipoprotein (IDL) + LDL] and relates well to apo-B levels [23]. Treatment targets for dyslipidaemia in overweight and obese patients, as well as in the general population, are primarily based on results from clinical trials and are modulated according to the level of total cardiovascular risk (see below). Primary target for cardiovascular disease prevention should be a reduction in LDL cholesterol. Treatment targets for LDL cholesterol are set to less than 70 mg/dl in patients with very high cardiovascular risk, to less than 100 mg/dl in patients with high cardiovascular risk and to less than 115 mg/dl in patients with moderate cardiovascular risk [23]. Once the primary LDL target is achieved, the level of non-HDL cholesterol should be checked and targeted. Treatment targets for non-HDL cholesterol are set 30 mg/dl higher than the corresponding target for LDL cholesterol [23].

Prediabetes/diabetes, hypertension, hypertriglyceridaemia and low HDL cholesterol levels are frequently clustered in patients with abdominal obesity. This cluster of metabolic abnormalities has been labelled as the metabolic syndrome, and specific diagnostic criteria have been proposed [24] (Table 15.4). The superiority of the metabolic syndrome over the combined evaluation of the single risk factors as an indicator of cardiovascular risk has been criticised, but the diagnosis of metabolic syndrome still remains useful in clinical practice for the rapid identification of overweight and obese patients with a worse cardiovascular and metabolic fate. Patients with the metabolic syndrome frequently have other accompanying metabolic abnormalities, like insulin resistance, low-grade chronic inflammation and a prothrombotic state. However, the routine measurement of insulin resistance (e.g. plasma insulin), proinflammatory state (e.g. high-sensitivity C-reactive protein) or prothrombotic state (e.g. fibrinogen or PAI-1) is not yet supported by adequate evidence, and it is not recommended [24].
Jul 5, 2017 | Posted by in UROLOGY | Comments Off on Clinical Evaluation

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