New obesity classification criteria as a tool for bariatric surgery indication

Table 1 Obesity classification

Publication	Year	Definition
Normal weight obesity - NWO
De Lorenzo et al[141]	2005	Normal weight (by BMI) + PBF > 30 (dual X-ray absorptiometry) + ↓ lean body composition of the left leg. Do not have metabolic syndrome
Di Renzo et al[162]	2006	NWO syndrome is characterized by wild type homozygotes genotypes regarding IL-15 R-α and MTHFR 677C/T polymorphism
De Lorenzo et al[147]	2007	↑ concentrations of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-8, TNF-α in NWO respect to non obese group
Di Renzo et al[160]	2007	The allele 2 (A2) of IL-1 receptor antagonist (Ra) in NWO subjects was associated with ↑ of IL-1β plasma amount
Marques-Vidal et al[151]	2008	Normal weight (by BMI) + ↑PBF (Bioelectrical impedance) or fat mass index ≥ 8.3 kg/m2 (men) or ≥ 11.8 kg/m2 (women)
Di Renzo et al[161]	2008	Genotyping of -175 G/C IL-6 polymorphism: in G/G the serum IL-6 level of NWO (10.70 ± 2.52 pg/mL) and obese (10.67 ± 1.09 pg/mL) was significantly higher compared with NWL women (5.54 ± 1.51 pg/mL). Positive correlation between PBF and plasma IL-6 and between HOMA-IR and plasma IL-6 only in NWO e obese G/G carrier
Marques-Vidal et al[149]	2010	↑ blood pressure, ↑ lipid levels and ↑ prevalence of dyslipidaemia [OR = 1.90 (1.34-2.68)] and fasting hyperglycaemia [OR = 1.63 (1.10-2.42)] respect to lean women, whereas no differences were found between NWO and overweight women.
Di Renzo et al[159]	2010	↓ glutathione and nitric oxide metabolites were significantly lower in pre-obese-obese and NWO compared to normal weight individuals. Lipid peroxide levels negatively correlated to FFM% and positively correlated to PBF, IL-15, TNF-α, insulin, total cholesterol, LDL, and triglycerides
Romero-Corral et al[157]	2010	NWO not manifest the metabolic syndrome, despite a cluster of metabolic and genetic features such as the higher prevalence of dyslipidemia, hypertension (men), CVD (women), and a 2.2-fold increased risk of CVD mortality (women) compared with those with low PBF
Kim et al[156]	2013	Normal weight (by BMI) + ↑ PBF
Madeira et al[155]	2013	Normal weight (by BMI < 25) + Sum of triceps and subscapular skinfolds > 90th percentiles
Di Renzo et al[164]	2013	G/A -308 TNF-α polymorphism contributes to sarcopenic obesity susceptibility in NWO
Di Renzo et al[165]	2014	TP53 codon 72 in exon 4 polymorphism was associated to the reduction of appendicular skeletal muscle mass index in NWO, leading to increase of sarcopenia risk
Oliveros et al[146]	2014	Normal BMI, ↑ PBF content and at increased risk for metabolic dysregulation, systemic inflammation and mortality
Jean et al[158]	2014	Highlight the importance of PBF correct assessment and body fat distribution in the clinical setting to identify NWO phenotype
Metabolically healty obese - MHO
Bonora et al[178]	1998	Subgroup of obese individuals with a normal metabolic response
Sims[179]	2001	The MHO subset include family members with uncomplicated obesity, early onset of the obesity, fasting plasma insulin within normal range, and normal distribution of the excess fat
Karelis et al[190]	2004	↑ Fat mass + Normal Metabolic profile + ↑ insulin sensitivity
Karelis et al[143]	2005	Favorable inflammation profile: ↓ hsCRP, ↓α-1 antitrypsin levels compared with insulin-resistant women, suggesting that lower inflammation state could play a role in the protection of this phenotype
Succurro et al[171]	2008	Respect to MONW, MHO have a healthier metabolic risk profile and ↑ disposition index (insulin sensitivity x insulin secretion)
Wildman et al[50]	2008	In NHANES sample, it was found a prevalence of 32% among obese adults over the age of 20
Arnlöv et al[192]	2010	MHO individuals were at an increased risk of major CVD events as compared to MHNW individuals in follow-up periods (> 15 yr)
Eshtiaghi et al[194]	2014	MHO phenotype over a 10 yr period progressed to frank metabolic syndrome
Achilike et al[196]	2015	Among subjects classified as MHO at baseline, almost half (47.6%) of them progressed to metabolically unhealthy obese (MUO) within the 7.8-yr follow-up period
Shaharyar et al[195]	2015	Both MHO individuals and MONW phenotypes were associated with ↑ high hsCRP, and hepatic steatosis
Metabolically obese but normal weight - MONW
Ruderman et al[166]	1981	Subtle increase in adiposity and/or hyperinsulinism creating obese associated diseases in normal weight (by standard weight tables)
Ruderman et al[167]	1998	CHD, T2DM and other disorders associated with obesity + normal weight (< 115% of ideal body weight or BMI < 28 kg/m2)
Dvorak et al[168]	1999	Impaired insulin sensitivity, BMI < 26.3 kg/m2↑ total fat mass (+20%), ↑ PBF (+16%) (dual x-ray absorptiometry), ↑ subcutaneous fat (+33%), ↑ visceral fat (+26%)
Esposito et al[176]	2004	↑ inflammation biomarkers, TNF-α and IL-6, in as a result of the larger visceral fat areas in this group
Conus et al[169]	2004	Insulin sensitivity determined by HOMA > 1.69 with normal weight (by BMI < 25 kg/m2), ↑PBF (dualX-ray absorptiometry), ↓ FFM, ↓ physical activity energy expenditure, ↓ peak oxygen uptake
Meigs et al[170]	2006	BMI < 25 kg/m2 + Metabolic Syndrome criteria/insulin resistance
Succurro et al[171]	2008	Normal weight (by BMI) + Impaired insulin sensitivity, ↑ visceral adiposity, ↓ HDL, ↑ fasting glucose, ↑ triglycerides, hypertension
Thomas et al[175]	2012	According magnetic resonance imaging, they refined MONW phenotype and renaming this sub-phenotype as “thin-on-the-outside fat-on-the-inside” (TOFI), with a higher ratio of visceral:subcutaneous abdominal adipose tissue
Eckel et al[172]	2015	↑ waist circumference (women: 75.5 cm vs 73.1 cm; men: 88.0 cm vs 85.1 cm), ↑ HbA1c (6.1% vs 5.3%), ↑ triglycerides (1.47 mmol/L vs 1.11 mmol/L), and ↑ hsCRP (0.81 mg/L vs 0.51 mg/L) , ↓ HDL (1.28 mmol/L vs 1.49 mmol/L) and ↓ adiponectin (6.32 μg/L vs 8.25 μg/mL)
Du et al[173]	2015	Lipid accumulation product and visceral adiposity index, two markers of visceral obesity, identify the MONW phenotype
Metabolically unhealthy obese - MUO
Alberti et al[201]	2005	MUO subjects are characterized by a BMI ≥ 30 kg/m2, a PBF > 30% and high visceral fat mass, closely linked to the development of the metabolic syndrome, T2DM, and atherosclerotic cardiovascular disease
Fabbrini et al[47]	2009	In MAO subjects, but not MNO subjects, moderate weight exacerbated several metabolic risk factors for CVD: ↑ blood pressure, ↑ plasma triglyceride,↑ in intra hepatic triglyceride, ↑ VLDL apoB100 and ↓ plasma adiponectin concentrations and insulin sensitivity in the liver, skeletal muscle, and adipose tissues, ↓ adipose tissue expression of genes involved in glucose uptake and lipogenesis
O'Connell et al[210]	2010	MUO and obese with T2DM subjects had a omental adipocyte size greater than MHO, moreover MUO group had an intermediate degree of steatosis (43%) respect to MHO (3%) and obese with T2DM (74%).
Di Daniele et al[202]	2013	6 mo of dietary intervention based on Italian Mediterranean Diet in “at risk” obese subjects, determined a reduction (-52%) in the prevalence of the metabolic syndrome and a reduction in terms of waist circumference, BMI and total body weight.
Calanna et al[211]	2013	At-risk obese individuals showed ↑ plasma glucose dependent insulinotropic polypeptide, ↓ post-glucose load glucagone-like-peptide-1, and ↑ levels at baseline and after glucose load, indicating inappropriate glucagone suppression

BMI: Body mass index; PBF: Percentage of total body fat; NWO: Normal weight obesity; NWL: Normal weight lean; FFM: Fat free mass; HOMA: Homeostatic model assessment; LDL: Low density lipoprotein; HDL: High density lipoprotein; CVD: Cardiovascular disease; MHO: Metabolically healthy obese; HbA1c: Glycated haemoglobin; hsCRP: High sensitive C-reactive protein; MHNW: Metabolically healthy normal weight; MONW: Metabolically obese normal weight; MUO: Metabolically unhealthy obese; CHD: Chronic heart disease; T2DM: Type 2 diabetes mellitus; MAO: Metabolic abnormal obese; MNO: Metabolically normal obese.