Severe Quantitative Scale of Acanthosis Nigricans in Neck is Associated with Abdominal Obesity, HOMA-IR, and Hyperlipidemia in Obese Children from Mexico City: A Cross-Sectional Study

Burguete-García, Ana I.; Ramírez Valverde, Alan Gilberto; Espinoza-León, Meztli; Vázquez, Isaac Sánchez; Estrada Ramírez, Evelyn Yazmín; Maldonado-López, Itzel; Martínez, Alfredo Lagunas; Diaz Benítez, Cinthya Estefhany; Araujo, Roberto Karam; Fernández-Madinaveitia, Diana; Anides Fonseca, Adriana E.; Cruz, Miguel; de Jesús Peralta Romero, José

doi:https://doi.org/10.1155/2022/2906189

Dermatology Research and Practice

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Abstract Introduction Methods Results Discussion Abbreviations Data Availability Conflicts of Interest Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2022 | Article ID 2906189 | https://doi.org/10.1155/2022/2906189

Severe Quantitative Scale of Acanthosis Nigricans in Neck is Associated with Abdominal Obesity, HOMA-IR, and Hyperlipidemia in Obese Children from Mexico City: A Cross-Sectional Study

Ana I. Burguete-García,¹Alan Gilberto Ramírez Valverde,²Meztli Espinoza-León,²Isaac Sánchez Vázquez,^2,3Evelyn Yazmín Estrada Ramírez,²Itzel Maldonado-López,²Alfredo Lagunas Martínez,¹Cinthya Estefhany Diaz Benítez,¹Roberto Karam Araujo,⁴Diana Fernández-Madinaveitia,⁵Adriana E. Anides Fonseca,⁵and Miguel Cruz² et al.

Academic Editor: Mohamed Elsaie

Received14 Sept 2021

Revised07 Feb 2022

Accepted12 Mar 2022

Published28 Mar 2022

Abstract

Background. Acanthosis nigricans (AN) is a clinical sign that commonly occurs in obesity; however, its specificity and sensitivity have been controversial. It is unknown if AN severity degree can be a useful marker for cardiometabolic disorders screening. We suggest that the stratified analysis of AN severity degree in neck by Burke’s scale could be a useful tool in the screening of cardiometabolic alterations in obese children. Objective. The aim of this study was the association of AN severity degree in neck by Burke’s scale with anthropometric, biochemical, and inflammatory parameters in obese school-age children from Mexico City. Methods. A cross-sectional study was conducted, including 95 obese school-age children stratified by AN severity degree in neck by Burke’s scale. Anthropometric and fasting biochemical measurements were determined. Variables were compared by x² test for frequencies and one-way ANOVA with Bonferroni posttest for continuous variables. Linear regression analysis adjusted by gender, BMI, and age was performed to evaluate the association between AN severity degree and cardiometabolic alterations. Statistical significance was set at . Results. As AN severity degree in neck by Burke’s scale increased, diastolic blood pressure () and triglycerides () significantly increased and adiponectin significantly decreased (). Positive associations between grade 3 AN and waist circumference, HOMA-IR, triglycerides, total cholesterol, and LDL cholesterol were observed. Conclusion. Our findings could be used to identify an easier clinical tool to prevent obesity progression and its complications in pediatrics. There are no similar studies.

1. Introduction

Obesity is an important public health issue in the world. In Mexico, the combined prevalence of overweight and obesity in the school-age population was 34.4% in 2012 and 32.2% in 2016, and high estimates represent an urgency in the care and prevention of complications from the early stages of life [1]. Despite the declining trend, the prevalence of overweight and obesity likely did not decrease as the prevalence in rural areas increased [1, 2]. Studies have suggested that up to 80% of overweight children will become obese adults [3]. Obesity is associated with dyslipidemia, insulin resistance (IR), and glucose intolerance (GI), which are the main risk factors for the development of type 2 diabetes and cardiovascular diseases. One of the most deleterious metabolic derangements of obesity is dyslipidemia, both are frequently associated, because there is some phenotype of dyslipidemia when the body mass index is higher. Dyslipidemia is a multifactorial condition that can occur in normal-weight and obese patients; however, obese individuals exhibit a lipid profile known as atherogenic dyslipidemia, characterized by increased concentrations of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and decreased concentrations of high-density lipoprotein cholesterol (HDL-C), considered as a risk marker for metabolic syndrome and diseases cardiovascular. There is still a long way to go to elucidate the complex pathogenesis of obesity dyslipidemia, but it has been observed that obesity mediated by an increase in fatty acid intake leads to dyslipidemia, leading to the development of IR in peripheral tissues and intravascular lipolysis [4] and enhancing vascular and liver damage to develop at an early age in obese children [5]. Specific biochemical and inflammatory markers indicate the onset and severity of obesity, including adipokines and the homeostatic model assessment for insulin resistance (HOMA-IR); however, not all medical services have access to these tests. Therefore, validating and stratifying phenotypic characteristics as clinical markers associated with metabolic alterations due to obesity are necessary, with the intention of being used in primary prevention.

Acanthosis nigricans (AN) is recognized as the most frequent dermatosis in obesity. Clinically, AN lesions are described as thickened, symmetrical grayish-brown hyperpigmentation plaques. Histopathologically, papillomatosis and hyperkeratosis are observed. AN is often found in folds and areas of flexion and is most frequently located in the neck [6]. AN is a clinical sign that has been associated with obesity, IR [7–10], hormonal disorders [11], lipoinflammation mediated by leptin and adiponectin [12], the use of certain medications and supplements, and some types of cancer. AN presence in obesity is often described by its severity and the patient’s family history and race [13, 14]. The association of AN with alterations described in some populations is usually controversial because of the difficulty of establishing the sensitivity and specificity due to ethnicity and phototype [15–17], rendering incidence and prevalence studies difficult in different populations including children [18–22].

Different epidemiological studies have reported AN incidence of approximately 7% in general population, but it can be present in up to 74% of obese people [23].

Few AN prevalence studies in school-age children have been reported; therefore, AN should not be underestimated, especially in obese children, who are vulnerable to cardiometabolic disturbances [24]. However, there are still some uncertainties and conflicts to determine if AN can be of clinical utility in children, due to AN being a dermatological lesion with variable frequency that usually appears at birth, in school age or adolescence. On rare occasions, AN may be associated with a generalized affectation, its presence in children should not necessarily be considered as pathological [25, 26], and its sensitivity as a clinical tool associated with cardiometabolic alterations in children could be controversial; however, its study becomes important due to AN frequency is higher in obese children.

While several classification systems can be used to diagnose AN [13, 27]. Burke’s scale, which was developed in a Mexican American population, is the most used system. Burke’s scale classifies AN according to the severity on a scale of 0–4 based on the number of affected areas [28]. Neck is the most accessible and common anatomical region for its study. Few studies in Mexican children have described the association of the presence of AN with anthropometric, biochemical, and inflammatory parameters [29, 30]; however, no quantification and correlation of the severity of AN with cardiometabolic alterations at different sites are provided. Currently, it’s unknown if AN severity degree in neck by Burke’s scale can be a useful marker in obese children for screening for cardiometabolic alterations. Stratified analysis of AN severity degree in neck by Burke’s scale could provide evidence of the sensitivity and specificity in screening. The aim of this study was to determine the association of AN severity degree in neck by Burke’s scale with anthropometric, biochemical, and inflammatory parameters in obese, school-age children from Mexico City. Our findings could suggest in the future the clinical use of AN severity degree in neck by Burke’s scale as an easily useful tool in screening for the progression of obesity disorders in pediatric patients.

2. Material and Methods

2.1. Study Design and Population

This cross-sectional study was conducted between February and June 2016. Participants were collected using a convenience sampling method by nonprobabilistic consecutive selection, out of a total of 1,500 children registers from a database. We included 95 school-age children with obesity diagnosis from 4 recreational and social centers in Mexico City (north, south, east, and west), Instituto Mexicano del Seguro Social (IMSS) insured, who reported anthropometric and biochemical parameters, blood pressure, HOMA-IR, adiponectin, leptin, and AN severity degree in neck by Burke’s scale registered in the database. The sample was stratified into 5 groups according to AN severity degree in neck by Burke’s scale on a 0–4 level [28].

Patients with a history or current diagnosis of any type of cancer, thyroid disorders, psoriasis, atopic dermatitis, autoimmune diseases, endocrinological diseases, liver disease, users of supplements, antioxidants, steroids, antihistamines or diet, physical activity, or under pharmacological weight loss treatment were excluded. Children with BMI ≥98th percentile were also excluded.

2.2. Anthropometric Profile

All participants were weighed using a digital scale (Seca, Hamburg, Germany), and height was measured using a portable stadiometer (Seca). Waist circumference (WC) of each participant was measured at the midpoint between the lowest rib and the iliac crest after a normal exhalation in the standing position. Obesity was determined using the calculated body mass index (BMI) and classified according to the standards reported by the Center for Disease Control (Atlanta, GA, USA) in 2000 (obesity ≥95th percentile of BMI) [31].

2.3. Blood Pressure

Blood pressure (BP) was measured using a mercurial sphygmomanometer (ALPK2, Tokyo, Japan) with the appropriate cuff size for arm length following the North American Task Force 2004 Guidelines. The BP was measured in the right arm with the participant in a sitting position. Two BP measurements were obtained with a resting time of 5 min between each measurement. The mean of the two measurements was used in the analyses [32].

2.4. Acanthosis Nigricans

Burke’s scale was used to determine the severity of AN in the neck. When AN was not detectable on close inspection, the severity was considered grade 0. Grade 1 severity was defined as AN is clearly present on close visual inspection but not visible to the casual observer and not measurable. Grade 2 severity was defined as AN limited to the base of the skull that did not extend to the lateral margins of the neck (typically <7.62 cm in breadth). Grade 3 severity was defined as AN extending to the lateral margins of the neck and the posterior border of the sternocleidomastoid (typically spanning 7.62–15.24 cm) that was not visible when the participant was observed from the front. Grade 4 severity was defined as AN extending anteriorly (typically >15.24 cm in breadth) that was visible when the participant was observed from the front [28].

2.5. Biochemical Profile

The following biochemical data were recorded: fasting glucose (mg/dL), insulin (µU/ml), total cholesterol (mg/dL), LDL-C (mg/dL), HDL-C (mg/dL), and triglycerides (mg/dL). These parameters were measured using the ILab 650 Clinical Chemistry System (Instrumentation Laboratory, Barcelona Spain) and Advia Centaur CP Immunoassay System (Siemens, Berlin, Germany). Adiponectin and leptin were also included and measured using the ELISA method (Human ELISA Kit, Invitrogen, Thermo Fisher Scientific, California, USA). Insulin sensitivity was calculated by the Homeostatic Model of Insulin Resistance (HOMA-IR) using the following equation: [(fasting glucose (mg/dL)) (fasting insulin (μU/mL))/405] [33, 34].

2.6. Ethical Considerations

This study was approved by the Research and Bioethics Committee of the IMSS (registration number R-2012-785–071). Written informed consent was obtained from the parents of each participant prior to the study.

2.7. Statistical Analysis

Variables are reported as means and standard deviations, as well as percentages, and the normality distribution was evaluated by the Shapiro–Wilk test. Variables were compared using a chi-square test for frequencies and one-way ANOVA with Bonferroni posttest for continuous variables to assess the significance of differences in Burke’s scale 0 versus 1, 2, 3, and 4. To evaluate the association of the severity of AN in the neck with WC, HOMA-IR, and the lipid profile, a linear regression analysis adjusted by sex, BMI, and age was performed.

History of type 2 diabetes, overweight/obesity, age, and sex were analyzed first and variables that resulted in <10% change were not included in the subsequent analyses. Each covariate and its effect on the estimator were evaluated, and the final model included overweight or obesity, age, and sex. All analyses were conducted using Stata, SE v11.0 (StataCorp, US) and Epi Info^TM 3.3.2 (CDC, Atlanta, Georgia, US) software. Statistical significance was set at [31].

3. Results

A total of 95 children were analyzed. The participants’ characteristics are listed in Table 1. The presence of AN in the neck in obese children was not significantly different between participants with a family history of obesity and diabetes and those without. Diastolic BP () and triglycerides () were significantly increased in the groups as the severity of AN increased. Adiponectin concentration significantly decreased () as AN severity degree in neck by Burke’s scale increased. BMI, WC, insulin, HOMA-IR, total cholesterol, LDL-C, and leptin increased as the severity of AN increased and the glucose and HDL-C decreased as the severity of AN increased, though the differences between the groups were not significant.

Linear regression analysis was performed to evaluate the association of AN severity degree in neck by Burke’s scale with WC, HOMA-IR, and the lipid profile is listed in Table 2.

Our results showed that grade 3 of AN severity degree in neck by Burke’s scale was associated with WC (Coef. = 5.49, Std. Err. 2.31, CI: 0.88; 10.08, ), HOMA-IR (Coef. = 1.43, Std. Err. 0.58, CI: 0.27; 2.59, ), triglycerides (Coef. = 44.20, Std. Err. 16.57, CI: 11.24; 77.16, ), total cholesterol (Coef. = 29.51, Std. Err. 12.28, CI: 4.60; 54.42, ), and LDL-C (Coef. = 26.94, Std. Err. 10.10, CI: 6.85; 47.03, ).

4. Discussion

We report that grade 3 of AN severity degree in neck by Burke’s scale is associated with increased WC, triglycerides, LDL-C, total cholesterol, and HOMA-IR. The results could be of clinical utility as a screening method in the early stages of life, and we observe that most obese children have metabolic disorders related to high cardiovascular risk in the future. It has been recognized that AN is the most frequent dermatosis in obesity [35], and its presence has been reported to be directly proportional to the degree of fatness [36]. Also, the prevalence of AN in overweight or obese children has been reported as up to 60% [37]. AN lesions are easily recognized via an inspection of the skin and should be carefully monitored in obese patients. No study has described whether AN severity degree in neck by Burke’s scale could be a clinical indicator associated with cardiometabolic alterations in school-age children. Thus, our research showed a potential use for primary prevention.

In this study, 74/95 (77.87%) obese, school-aged participants presented AN in the neck. Among the participants with a family history of type 2 diabetes, 66.66% had ≥ grade 1 AN in this study, which is higher than that previously reported in the San Antonio Family Diabetes Study [28], which found that 41.1% of participants with a family history of type 2 diabetes had ≥ grade 1 AN, which correlated with fasting insulin and BMI.

It has been reported that up to 30% of obese patients are metabolically healthy, have insulin sensitivity like healthy individuals, normal weight, decreased visceral fat, and lower cardiometabolic risk factors [38]; however, 74% of obese American adults have AN and increased severity of obesity and insulin [18]. Therefore, we assume that the high prevalence of AN in our study may be attributed to the severity of BMI, hyperinsulinism, and IR. These reports are consistent with our results regarding obese children. Biochemical markers [39], heritage, and environment are risk factors for type 2 diabetes even in pediatric patients [40, 41].

In this study, positive associations between the presence of AN and variables associated with obesity were observed, which is consistent with previous studies that reported dyslipidemia and IR in school-age children in Mexico [29, 30]. Compared to other studies, our work suggests that AN severity degree in neck by Burke’s scale is mainly associated with IR and hypertriglyceridemia, and clinical alterations can lead to vascular alterations even in children.

Martínez-Rojano et al. reported increased systolic and diastolic BP in pediatric patients with AN and obesity compared to patients ≤ the 90th percentile for weight, though AN severity degree was not analyzed. In our study, diastolic BP increased with an increase of AN severity degree in neck by Burke’s scale [42]. Though the mechanism of increased BP in patients with AN is unknown, hypertension and obesity are strongly associated and can lead to cardiovascular disease and a higher risk of stroke, increasing the chance of early death or disability [43].

No statistically significant differences in fasting glucose concentrations were found between the groups in this study, which may be due to the higher fasting hyperinsulinism in participants with a higher increment of AN severity degree in neck by Burke’s scale. The presence of hyperinsulinism in obese patients is usually associated with IR (measured as an increase in HOMA-IR) due to the increased insulin-like growth factor-1 (IGF-1) cell receptors in states of hyperinsulinemia. These receptors promote the epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), and the proliferation of epidermal keratinocytes and dermal fibroblasts when activated [44, 45]. Almost all of the participants in this study had IR, measured as a HOMA-IR concentration near the previously reported cutoff of 3.4 [46]. These results suggest that AN severity degree in neck by Burke’s scale can be used as a clinical predictor of IR measured as increases in HOMA-IR, which contribute to alterations in WC, fasting insulin, triglycerides, and HDL-C, are considered cardiometabolic risk factors in obese children [47]. Similar to previous studies, we found that WC, triglycerides, total cholesterol, LDL-C, and HOMA-IR were increased [48, 49] and associated with the presence of AN [50, 51]. Specifically, we found that these variables were associated with grade 3 of AN severity degree in neck by Burke’s scale (Table 2).

The presence of metabolic disorders is also represented by an inverse relationship between leptin and adiponectin concentrations in obese patients [52]. It is unclear why there is no correlation between WC, triglycerides, total cholesterol, LDL-C, or HOMA-IR with AN severity degree in neck by Burke’s scale grade 4 in our study, though it may be due to increased leptin concentrations that play a compensatory role in patients with insulin intolerance or resistance due to more severe obesity. Leptin concentrations are higher in obese patients than in those of normal weight, and our study shows that leptin concentrations also increase with the severity of AN severity degree in neck by Burke’s scale. When the mass of adipose tissue increases, the synthesis and secretion of leptin increase, stimulating a decrease in appetite, increase in energy expenditure, reduction in lipogenesis, and increase in lipolysis. Also, leptin upregulates proinflammatory cytokines such as interleukin 6, which is associated with dyslipidemias, IR, and type 2 diabetes [53]. In contrast, hyperinsulinemia [54] and IR are indirectly related to hyperleptinemia [55].

Adiponectin has anti-inflammatory properties and downregulates the expression and release of several proinflammatory immune mediators. A leptin/adiponectin imbalance may be an important risk factor of developing type 2 diabetes and cardiovascular diseases associated with abdominal obesity [52]. Adiponectin concentration has been reported to be a risk factor for the development of type 2 diabetes in children [56]. In addition, decreased adiponectin and increased IR are risk factors for metabolic syndrome [57]. The association of adiponectin and dyslipidemias is based on the fact that adiponectin exhibits its effects through the sensitivity of the body to insulin and the oxidation of fatty acids [58, 59] via the activation of several signaling molecules including adenosine monophosphate-activated protein kinase, p38-MAPK, JNK, the PPARγ transcription factor, and NF-ƙβ in various tissues. These signals are transduced via the adiponectin receptor signaling pathway [60, 61] and may have a genetic component [62].

To our knowledge, this is the first study to report that AN severity degree in neck by Burke’s scale grade 3 is related to metabolic changes in obese children, suggesting that AN severity degree in neck by Burke’s scale can be used as a clinical predictor for IR and hypertriglyceridemia that allows for timely treatments through changes in lifestyle, supplements, or medications [63].

However, this study has some limitations as follows:(1) We recognize that our study group analyzed was small due to the type of sampling; however, there are no similar studies reported previously and it could be considered as a pilot, suggesting that it be carried out on a large scale in the future by increasing the size of the sample in order to determine sensitivity as a clinical tool of AN severity degree in neck by Burke’s scale in obese children for screening for cardiometabolic alterations. Despite the size of the sample, our study showed statistically significant associations. (2) We did not perform an analysis of consumption frequency or 24 h dietary recall, which could infer the results; however, none of the included participants carried out any type of pharmacological or nonpharmacological treatment such as diet, physical activity [64], or lifestyle changes to reduce obesity. In addition, they did not know the presence of cardiometabolic alterations at the time of accepting their participation in the study. (3) Clinical and biochemical data related to changes in puberty and growth stages of the participants were not collected, which may influence the onset behavior of IR and AN severity degree [11]; although an association with the presence of early puberty mainly in women, it has not yet been completely clarified. (4) Our cross-sectional study only permits the establishment of associations of AN severity degree in neck by Burke’s scale with cardiometabolic alteration but does not allow for the determination of causality. Efforts to clarify the causal relationship of the variables included in this study may yield new strategies according to screening approaches for obesity, IR, and related disorders. (5) Ancestry of the participants was not analyzed. It has been reported that patients with Native American ancestry have a genetic predisposition to dyslipidemia and the contribution to the presence of cardiometabolic alterations [65–67].

We assume that AN severity degree in neck by Burke’s scale could be used as a screening biomarker to obesity complications in vulnerable children; however, future research is required to identify its application through interventions, aimed at preventive measures for screening and early detection of obesity complications, including insulin resistance, dyslipidemia, and impaired fasting glucose, as well as the development of specialized multidisciplinary teams responsible for implementing the findings.

Abbreviations

AN:	Acanthosis nigricans
WC:	Waist circumference
HOMA-IR:	Homeostatic model assessment for insulin resistance
IR:	Insulin resistance
GI:	Glucose intolerance
IMSS:	Mexican Institute of Social Security
BMI:	Body mass index
BP:	Blood pressure
LDL-C:	Low-density lipoprotein cholesterol
HDL-C:	High-density lipoprotein cholesterol
IGF-1:	Insulin-like growth factor-1
EGFR:	Epidermal growth factor receptor
FGRF:	Fibroblast growth factor receptor
DBP:	Diastolic blood pressure
SBP:	Systolic blood pressure
FHOB:	Family history of obesity
FHT2D:	Family history of type 2 diabetes.

Data Availability

Registration number R-2012-785-071 for data used to support the findings of this study may be released upon application to the Research and Bioethics Committee of the Instituto Mexicano del Seguro Social (Mexican Social Security Institute) that can be contacted at COMITÉ DE ÉTICA EN INVESTIGACIÓN DEL IMSS: Avenida Cuauhtémoc 330 4° piso Bloque “B” de la Unidad de Congresos, Colonia Doctores. México, D.F., CP 06720. Teléfono (55) 56276900 extensión 21216 en horarios de 9 a 16 horas de lunes a viernes, Correo electrónico: [email protected].

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Acknowledgments

The authors thank the participants of the present study and the team of the Biochemistry Unit at IMSS for their technical assistance. The authors also thank the Departamento de Epidemiología Genética from the Instituto Nacional de Salud Pública (INSP), the staff of the Sports Unit in Cuauhtémoc, Morelos, Independencia and Netzahualcoyotl, and the staff at the Unit for Medical Research at the High Specialization Hospital (Hospital de Alta Especialidad Médica). The authors would like to thank Dr. Bernardo Sepúlveda, IMSS, in Mexico City and the Coordinación de Bienestar Social of the Dirección de Prestaciones Económicas y Sociales del IMSS in Mexico City. The study was supported by the National Council of Sciences and Technology (CONACYT, grant numbers SSA/IMSS/ISSSTE-CONACYT 2012-180808 and CONACYT SSA/IMSS/ISSSTE-CONACYT 2015-262133) and Instituto Mexicano del Seguro Social (IMSS 2011-785-012, registro Fis: FIS/IMSS/PROT/PRIO/10/011).

References

M Hernandez-Ávila, J Rivera-Dommarco, T Shamah-Levy, L Cuevas-Nasu, L. M Gómez-Acosta, and E. B Gaona-Pineda, National Mid-stage Health and Nutrition Survey 2016: Final Results Report], National Institute of Public Health, Cuernavaca, Mexico, 2016.
J. P Gutiérrez, J Rivera-Dommarco, T Shamah-Levy, S Villalpando-Hernández, A Franco, and L Cuevas-Nasu, National Survey of Health and Nutrition 2012. National Results, National Institute of Public Health, Cuernavaca, Mexico, 2012.
C Posadas-Romero, “[Obesity and metabolic síndrome in children and adolescents],” Revista de Endocrinología y Nutrición, vol. 13, pp. 45-46, 2005.
View at: Google Scholar
B. Klop, J. Elte, and M. Cabezas, “Dyslipidemia in obesity: mechanisms and potential targets,” Nutrients, vol. 5, no. 4, pp. 1218–1240, 2013.
View at: Publisher Site | Google Scholar
P Durán, N Piazza, L Trifone, C Agnestein, P Casavalle, and S De Grandis, “Consensus about risk factors for cardiovascular disease in pediatrics],” Archivos Argentinos de Pediatria, vol. 103, pp. 262–281, 2005.
View at: Google Scholar
R. A. Schwartz, “Acanthosis nigricans,” Journal of the American Academy of Dermatology, vol. 31, no. 1, pp. 1–19, 1994.
View at: Publisher Site | Google Scholar
A. Plascencia Gómez, M. E. Vega Memije, M. Torres Tamayo, and A. A. Rodríguez Carreón, “Skin disorders in overweight and obese patients and their relationship with insulin,” Actas Dermo-Sifiliográficas, vol. 105, no. 2, pp. 178–185, 2014.
View at: Publisher Site | Google Scholar
E García-García, J Ramos-Lao, M. R Jimenez-Liria, J Aguirre, M. A Llamas, and M Leyva, “[Insulin resistance in obese children and adolescents],” Av Diabetol, vol. 20, pp. 43–47, 2004.
View at: Google Scholar
V Hirschler, C Aranda, A Oneto, C Gonzalez, A. M Delfino, and G Clemente, “[Is acanthosis nigricans a sign of insulin resistance among obese adolescents?],” Archivos Argentinos de Pediatria, vol. 102, pp. 115–120, 2004.
View at: Google Scholar
C. E. N. Kluczynik, L. S. Mariz, L. C. F. Souza, G. B. Solano, F. C. d. L. Albuquerque, and C. C. M. Medeiros, “Acanthosis nigricans and insulin resistance in overweight children and adolescents,” Anais Brasileiros de Dermatologia, vol. 87, no. 4, pp. 531–537, 2012.
View at: Publisher Site | Google Scholar
C. A. Stuart, E. J. Peters, M. J. Prince, G. Richards, A. Cavallo, and W. J. Meyer, “Insulin resistance with acanthosis nigricans: the roles of obesity and androgen excess,” Metabolism, vol. 35, no. 3, pp. 197–205, 1986.
View at: Publisher Site | Google Scholar
S. K. Hegazy and N. E. El-Ashmawy, “Leptin and c-reactive protein are implicated in the pathogenesis of skin tags,” Journal of Diabetes Research and Clinical Metabolism, vol. 2, no. 1, p. 13, 2013.
View at: Publisher Site | Google Scholar
H. O. Curth, “Classification of acanthosis nigricans,” International Journal of Dermatology, vol. 15, no. 8, pp. 592-593, 1976.
View at: Publisher Site | Google Scholar
M. T. Barbato, P. R. Criado, A. K. d. Silva, E. Averbeck, M. B. Guerine, and N. B. d. Sá, “Association of acanthosis nigricans and skin tags with insulin resistance,” Anais Brasileiros de Dermatologia, vol. 87, no. 1, pp. 97–104, 2012.
View at: Publisher Site | Google Scholar
J. C López-Alvarenga, L García-Hidalgo, M. V Landa-Anell, R Santos-Gómez, J González-Barranco, and A Comuzzie, “Influence of skin color on the diagnostic utility of clinical acanthosis nigricans to predict insulin resistance in obese patients,” Archives of Medical Research, vol. 37, pp. 744–748, 2006.
View at: Google Scholar
L Rafalson, T. H Pham, S. M Willi, M Marcus, A Jessup, and T Baranowski, “The association between acanthosis nigricans and dysglycemia in an ethnically diverse group of eighth grade students,” Obesity, vol. 21, pp. E328–E333, 2013.
View at: Publisher Site | Google Scholar
P González-Fernández, E Cabrera-Rode, and M. A Oti-Gil, “Insulin resistance and family history of diabetes in obese children and with and without acanthosis nigricans,” Revista Cubana de Endocrinología, vol. 22, pp. 210–224, 2011.
View at: Google Scholar
J. A. Hud Jr, J. B Cohen, J. M Wagner, and P. D Cruz Jr, “Prevalence and significance of acanthosis nigricans in an adult obese population,” Archives of Dermatology, vol. 128, no. 7, pp. 941–944, 1992.
View at: Publisher Site | Google Scholar
C. A. Stuart, C. J. Pate, and E. J. Peters, “Prevalence of acanthosis nigricans in an unselected population,” The American Journal of Medicine, vol. 87, no. 3, pp. 269–272, 1989.
View at: Publisher Site | Google Scholar
J. P Chalco-Orrego, C. A Bada-Mancilla, and R. A Rojas-Galarza, “[Children who are overweight and acanthosis nigricans have a higher risk of having high blood pressure],” Evidence Pediatrition, vol. 3, p. 7, 2007.
View at: Google Scholar
S Muzzo, E Rosales, I Miranda, L Yates, and A Passeron, “Prevalence and characteristics of incidental hyperglucemia in children,” Revista Chilena de Nutricion, vol. 34, pp. 233–239, 2007.
View at: Publisher Site | Google Scholar
J. S. Aranibar, “Acanthosis nigricans and hyperinsulinemia in obese children and adolescents,” Paediatrica, vol. 8, pp. 1–4, 2006.
View at: Google Scholar
A. S. Dassanayake, A. Kasturiratne, M. A. Niriella et al., “Prevalence of Acanthosis Nigricans in an urban population in Sri Lanka and its utility to detect metabolic syndrome,” BMC Research Notes, vol. 4, no. 1, p. 25, 2011.
View at: Publisher Site | Google Scholar
A. Maguolo and C. Maffeis, “Acanthosis nigricans in childhood: a cutaneous marker that should not be underestimated, especially in obese children,” Acta Paediatrica, vol. 109, no. 3, pp. 481–487, 2020.
View at: Publisher Site | Google Scholar
D. S. Skiljevic, M. M. Nikolic, A. Jakovljevic, and D. D. Dobrosavljevic, “Generalized acanthosis nigricans in early childhood,” Pediatric Dermatology, vol. 18, no. 3, pp. 213–216, 2001.
View at: Publisher Site | Google Scholar
A. Das, D. Datta, M. Kassir et al., “Acanthosis nigricans: a review,” Journal of Cosmetic Dermatology, vol. 19, no. 8, pp. 1857–1865, 2020.
View at: Publisher Site | Google Scholar
E Hernández-Pérez, “On the classification of acanthosis nigricans,” International Journal of Dermatology, vol. 23, pp. 605-606, 1984.
View at: Google Scholar
J. P. Burke, D. E. Hale, H. P. Hazuda, and M. P. Stern, “A quantitative scale of acanthosis nigricans,” Diabetes Care, vol. 22, no. 10, pp. 1655–1659, 1999.
View at: Publisher Site | Google Scholar
R Valdés-Rodríguez, B Moncada-González, S. P Rivera-Rodríguez, C Aradillas-García, H Hernández-Rodríguez, and B Torres-Álvarez, “Skin tags and acanthosis nigricans: association with insulin resistance and overweight in Mexican children,” Gaceta Médica de México, vol. 147, pp. 297–302, 2011.
View at: Google Scholar
A Portillo-Pinedo, M. A Nuñez-Olivares, B Figueroa-Núñez, C Gómez-Alonso, and O Mejía-Rodríguez, “[Identification of acanthosis nigricans and its relationship with obesity and insulin resistance in children and adolescents in a primary care unit in Michoacan, Mexico],” Atención Familiar, vol. 18, pp. 31–34, 2011.
View at: Google Scholar
R. J Kuczmarski, C. L Ogden, S. S Guo, L. M Grummer-Strawn, K. M Flegal, and Z Mei, “CDC growth charts for the United States: methods and development,” Vital Health Statics, vol. 11, pp. 1–190, 2002.
View at: Google Scholar
Pediatric, “National high blood pressure education program working group on high blood pressure in children and adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents,” Pediatrics, vol. 114, pp. 555–576, 2004.
View at: Google Scholar
M Keskin, S Kurtoglu, M Kendirci, M. E Atabek, and C Yazici, “Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents,” Pediatrics, vol. 115, pp. e500–3, 2005.
View at: Publisher Site | Google Scholar
D. R. Matthews, J. P. Hosker, A. S. Rudenski, B. A. Naylor, D. F. Treacher, and R. C. Turner, “Homeostasis model assessment: insulin resistance and ?-cell function from fasting plasma glucose and insulin concentrations in man,” Diabetologia, vol. 28, no. 7, pp. 412–419, 1985.
View at: Publisher Site | Google Scholar
B. Guida, M. Nino, N. Perrino et al., “The impact of obesity on skin disease and epidermal permeability barrier status,” Journal of the European Academy of Dermatology and Venereology, vol. 24, no. 2, pp. 191–195, 2010.
View at: Publisher Site | Google Scholar
O García-Solís, D. E Medina-Castillo, J de la Cruz-López, S Huerta-Alvarado, I Díaz-Guadarrama, and F Velázquez-Canchola, “Obesity and dermatoses: a prospective and descriptive study at external consultation clinic Alfredo del Mazo Vélez, ISSEMyM Toluca, Mexico,” Dermatología Revista Mexicana, vol. 54, pp. 3–9, 2010.
View at: Google Scholar
A. S Karadağ, Y You, R Danarti, S Al-Khuzaei, and W Chen, “Acanthosis nigricans and the metabolic syndrome,” Clinics in Dermatology, vol. 36, pp. 48–53, 2018.
View at: Publisher Site | Google Scholar
A. Engin, “The definition and prevalence of obesity and metabolic syndrome,” Obesity and Lipotoxicity, vol. 960, pp. 1–17, 2017.
View at: Publisher Site | Google Scholar
C. Abraham and C. L. Rozmus, “Is acanthosis nigricans a reliable indicator for risk of type 2 diabetes in obese children and adolescents?” The Journal of School Nursing, vol. 28, no. 3, pp. 195–205, 2012.
View at: Publisher Site | Google Scholar
C. A Stuart, C. R Gilkison, B. S Keenan, and M Nagamani, “Hyperinsulinemia and acanthosis nigricans in African Americans,” Journal of the National Medical Association, vol. 89, pp. 523–527, 1997.
View at: Google Scholar
A. S. Kong, R. L. Williams, M. Smith et al., “Acanthosis nigricans and diabetes risk factors: prevalence in young persons seen in southwestern US primary care practices,” The Annals of Family Medicine, vol. 5, no. 3, pp. 202–208, 2007.
View at: Publisher Site | Google Scholar
H Martínez-Rojano, M Pizano-Zárate, B Sánchez-Jiménez, R Sámano, and A López-Portillo, “Acanthosis nigricans is associated with risk factors related to cardiovascular disease in Mexican children with obesity,” Nutricion Hospitalaria, vol. 33, p. 570, 2016.
View at: Google Scholar
D. K. Hayes, C. H. Denny, N. L. Keenan, J. B. Croft, A. A. Sundaram, and K. J. Greenlund, “Racial/ethnic and socioeconomic differences in multiple risk factors for heart disease and stroke in women: behavioral risk factor surveillance system, 2003,” Journal of Women's Health, vol. 15, no. 9, pp. 1000–1008, 2006.
View at: Publisher Site | Google Scholar
W Chug-Hsing, L Wei-De, B Da-Tian, C I-Ching, T Chang-Hai, and T Fuu-Jen, “Appearance of acanthosis nigricans may precede obesity: an involvement of the insulin/IGF receptor signaling pathway,” Biomedicine, vol. 3, pp. 82–87, 2013.
View at: Google Scholar
P. D Cruz Jr and J. A Hud Jr, “Excess insulin binding to insulin-like growth factor receptors: proposed mechanism for acanthosis nigricans,” Journal of Investigative Dermatology, vol. 98, pp. 82S–85S, 1992.
View at: Publisher Site | Google Scholar
B García-Cuartero, C García-Lacalle, C Jiménez-Lobo, A González-Vergaz, C Calvo-Rey, and M. J Alcázar-Villar, “[The HOMA and QUICKI indexes, and insulin and C-peptide levels in healthy children. Cut off points to identify metabolic syndrome in healthy children],” Anales de Pediatía, vol. 66, pp. 481–490, 2007.
View at: Google Scholar
Y. K. Koh, J. H. Lee, E. Y. Kim, and K. R. Moon, “Acanthosis Nigricans as a clinical predictor of insulin resistance in obese children,” Pediatric Gastroenterology, Hepatology & Nutrition, vol. 19, no. 4, pp. 251–258, 2016.
View at: Publisher Site | Google Scholar
A Pires, P Martins, A. M Pereira et al., “Insulin Resistance, dyslipidemia and cardiovascular changes in a group of obese children,” Arquivos Brasileiros de Cardiologia, vol. 104, pp. 266–273, 2015.
View at: Publisher Site | Google Scholar
E. Chedjou-Nono, S. Sap, S.-P. Choukem, I. Ngosso Tetanye, D. Nebongo, and O. Koki Ndombo, “Cardiometabolic profile of obese children in a sub-Saharan African setting: a cross-sectional study,” BMC Pediatrics, vol. 17, no. 1, p. 129, 2017.
View at: Publisher Site | Google Scholar
C Juárez-López, M Klünder- Klünder, P Medina-Bravo, A Madrigal-Azcárate, E Mass-Díaz, and S Flores-Huerta, “Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents,” BMC Public Health, vol. 10, p. 318, 2010.
View at: Google Scholar
A. S Kong, L Vanderbloemen, B Skipper et al., “Acanthosis nigricans predicts the clustering of metabolic syndrome components in hispanic elementary school-aged children,” Journal of Pediatric Endocrinology & Metabolism : Journal of Pediatric Endocrinology & Metabolism, vol. 25, pp. 1095–1102, 2012.
View at: Publisher Site | Google Scholar
P. López-Jaramillo, D. Gómez-Arbeláez, J. López-López, C. López-López, J. Martínez-Ortega, and A. Gómez-Rodríguez, “The role of leptin/adiponectin ratio in metabolic syndrome and diabetes,” Hormone Molecular Biology and Clinical Investigation, vol. 18, pp. 37–45, 2014.
View at: Google Scholar
H. Asakawa, K. Tokunaga, and F. Kawakami, “Relationship of leptin level with metabolic disorders and hypertension in Japanese type 2 diabetes mellitus patients,” Journal of Diabetes and Its Complications, vol. 15, no. 2, pp. 57–62, 2001.
View at: Publisher Site | Google Scholar
S. G. Wannamethee, J. Tchernova, P. Whincup et al., “Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease,” Atherosclerosis, vol. 191, no. 2, pp. 418–426, 2007.
View at: Publisher Site | Google Scholar
B. Thorand, A. Zierer, J. Baumert, C. Meisinger, C. Herder, and W. Koenig, “Associations between leptin and the leptin/adiponectin ratio and incident Type 2 diabetes in middle-aged men and women: results from the MONICA/KORA Augsburg Study 1984-2002,” Diabetic Medicine, vol. 27, no. 9, pp. 1004–1011, 2010.
View at: Publisher Site | Google Scholar
M. Cruz, R. García-Macedo, Y. García-Valerio et al., “Low adiponectin levels predict type 2 diabetes in Mexican children,” Diabetes Care, vol. 27, no. 6, pp. 1451–1453, 2004.
View at: Publisher Site | Google Scholar
M Klünder- Klünder, S Flores-Huerta, R García-Macedo, J Peralta-Romero, and M Cruz, “Adiponectin in eutrophic and obese children as a biomarker to predict metabolic syndrome and each of its components,” BMC Public Health, vol. 13, p. 88, 2013.
View at: Google Scholar
T. Yamauchi, J. Kamon, Y. Minokoshi et al., “Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase,” Nature Medicine, vol. 8, no. 11, pp. 1288–1295, 2002.
View at: Publisher Site | Google Scholar
A. H. Berg, T. P. Combs, X. Du, M. Brownlee, and P. E. Scherer, “The adipocyte-secreted protein Acrp30 enhances hepatic insulin action,” Nature Medicine, vol. 7, no. 8, pp. 947–953, 2001.
View at: Publisher Site | Google Scholar
T. Yamauchi, J. Kamon, Y. Ito et al., “Cloning of adiponectin receptors that mediate antidiabetic metabolic effects,” Nature, vol. 423, no. 6941, pp. 762–769, 2003.
View at: Publisher Site | Google Scholar
Y. T. Tang, T. Hu, M. Arterburn et al., “PAQR proteins: a novel membrane receptor family defined by an ancient7-transmembrane pass motif,” Journal of Molecular Evolution, vol. 61, no. 3, pp. 372–380, 2005.
View at: Publisher Site | Google Scholar
J. d. J. Peralta Romero, R. Karam Araujo, A. I. Burguete García et al., “ADIPOQ and ADIPOR2 gene polymorphisms: association with overweight/obesity in Mexican children,” Boletín Médico del Hospital Infantil de México, vol. 72, no. 1, pp. 26–33, 2015.
View at: Publisher Site | Google Scholar
J. Heshmati, M. Sepidarkish, N. Namazi et al., “Impact of dietary calcium supplement on circulating Lipoprotein concentrations and atherogenic indices in overweight and obese individuals: a systematic review,” Journal of Dietary Supplements, vol. 16, no. 3, pp. 357–367, 2019.
View at: Publisher Site | Google Scholar
L. M Cárdenas-Cárdenas, A. I Burguete-García, B. I Estrada-Velasco, C López-Islas, J Peralta-Romero, and M Cruz, “Leisure-time physical activity and cardiometabolic risk among children and adolescents,” The Journal of Pediatrics, vol. 91, pp. 136–142, 2015.
View at: Google Scholar
C. Stryjecki, J. Peralta-Romero, A. Alyass et al., “Association between PPAR-γ2 Pro12Ala genotype and insulin resistance is modified by circulating lipids in Mexican children,” Scientific Reports, vol. 6, no. 1, p. 24472, 2016.
View at: Publisher Site | Google Scholar
F Suárez-Sánchez, M Klünder- Klünder, J Valladares-Salgado, J Gómez-Zamudio, J Peralta-Romero, and D Meyre, “APOA5 and APOA1 polymorphisms are associated with triglyceride levels in Mexican children,” Pediatrition Obesity, vol. 12, pp. 330–336, 2017.
View at: Google Scholar
A. S. Kong, R. L. Williams, R. Rhyne et al., “Acanthosis nigricans: high prevalence and association with diabetes in a practice-based research network consortium--a PRImary care Multi-Ethnic network (PRIME Net) study,” The Journal of the American Board of Family Medicine, vol. 23, no. 4, pp. 476–485, 2010.
View at: Publisher Site | Google Scholar

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