Acanthosis Nigricans in Children and Adolescents with Type 1 Diabetes or Obesity: The Potential Interplay Role between Insulin Resistance and Excess Weight

Calcaterra, Valeria; Silvestri, Annalisa De; Schneider, Laura; Acunzo, Miriam; Vittoni, Viola; Meraviglia, Giulia; Bergamaschi, Francesco; Zuccotti, Gian Vincenzo; Mameli, Chiara

doi:10.3390/children8080710

Cited by 8 publications

(3 citation statements)

References 36 publications

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“…Acanthosis nigricans is a darkly pigmented, velvety, hyperkeratotic, papillomatous skin lesions in body folds such as the skin of the neck or axilla. The presence of acanthosis nigricans is due to acanthocytes' exposure to hyperinsulinemia, interacting with insulin-like growth factor-1 receptors on these cells[ 132 , 133 ]. Multiple skin tags are more sensitive than acanthosis nigricans in identifying abnormal glucose/insulin metabolism.…”

Section: Physical Examinationmentioning

confidence: 99%

Insulin-resistance in paediatric age: Its magnitude and implications

Al‐Biltagi¹,

Bediwy²,

Saeed³

2022

WJD

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Insulin resistance (IR) is insulin failure in normal plasma levels to adequately stimulate glucose uptake by the peripheral tissues. IR is becoming more common in children and adolescents than before. There is a strong association between obesity in children and adolescents, IR, and the metabolic syndrome components. IR shows marked variation among different races, crucial to understanding the possible cardiovascular risk, specifically in high-risk races or ethnic groups. Genetic causes of IR include insulin receptor mutations, mutations that stimulate autoantibody production against insulin receptors, or mutations that induce the formation of abnormal glucose transporter 4 molecules or plasma cell membrane glycoprotein-1 molecules; all induce abnormal energy pathways and end with the development of IR. The parallel increase of IR syndrome with the dramatic increase in the rate of obesity among children in the last few decades indicates the importance of environmental factors in increasing the rate of IR. Most patients with IR do not develop diabetes mellitus (DM) type-II. However, IR is a crucial risk factor to develop DM type-II in children. Diagnostic standards for IR in children are not yet established due to various causes. Direct measures of insulin sensitivity include the hyperinsulinemia euglycemic glucose clamp and the insulin-suppression test. Minimal model analysis of frequently sampled intravenous glucose tolerance test and oral glucose tolerance test provide an indirect estimate of metabolic insulin sensitivity/resistance. The main aim of the treatment of IR in children is to prevent the progression of compensated IR to decompensated IR, enhance insulin sensitivity, and treat possible complications. There are three main lines for treatment: Lifestyle and behavior modification, pharmacotherapy, and surgery. This review will discuss the magnitude, implications, diagnosis, and treatment of IR in children.

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Section: Physical Examinationmentioning

confidence: 99%

Insulin-resistance in paediatric age: Its magnitude and implications

Al‐Biltagi¹,

Bediwy²,

Saeed³

2022

WJD

View full text Add to dashboard Cite

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“…Calcaterra V. et al carried out a retrospective study on 138 patients newly diagnosed with DM type 1. Comparing the patients with AN (N = 7) with the 131 AN-free persons, the AN positive patients had higher BMIs (23.86 ± 4.95 versus 20.56 ± 4.21 kg/m 2 , p = 0.047), as well as higher estimated glucose disposal rates (eGDR) (9.26 ± 2.01 mg versus 10.55 ± 1.52 mg kg −1 min −1 , p = 0.0333) [ 101 ]. A study on Brazilian patients with DM type 1 (N = 1640) identified MS in 29.8% of individuals, with MS being correlated with AN (OR = 5.93, p < 0.001), female sex (OR = 1.95, p < 0.001), DM type 1 duration (OR = 1.04, p < 0.001), and family history of DM type 2 (OR = 1.36, p = 0.019), based on a self-reported color-race model.…”

Section: An and Dmmentioning

confidence: 99%

Acanthosis Nigricans: Pointer of Endocrine Entities

et al. 2022

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Acanthosis nigricans (AN) has been reported in relation to insulin resistance (IR). We aim to review AN through an endocrine and metabolic perspective focusing on IR in association with metabolic complications such as obesity, diabetes mellitus (DM), and metabolic syndrome (MS) with/without polycystic ovary syndrome (PCOS). We revised English papers on PubMed covering publications from the last 5 years. The current prevalence of AN varies from 4.5 to 74% (or even 100%, depending on the studied population), with equal distribution among females and males. Despite higher incidence with an age-dependent pattern, an alarming escalation of cases has been noted for obesity and MS in younger populations . Most frequent IR-associated sites are the neck, axilla, and knuckles, but unusual locations such as the face have also been reported. Quantitative scales such as Burke have been used to describe the severity of the dermatosis, particularly in correlation with IR elements. Dermoscopic examination are required, for instance, in cases with sulcus cutis, hyperpigmented spots, crista cutis, and papillary projections. A skin biopsy may be necessary, but it is not the rule. Both IR that clinically manifests with or without obesity/MS correlates with AN; most studies are cross-sectional, with only a few longitudinal. The approach varied from screening during school periodic checkups/protocols/programs to subgroups of individuals who were already known to be at high cardio-metabolic risk. AN was associated with type2DM, as well as type 1DM. Females with PCOS may already display metabolic complications in 60–80% of cases, with AN belonging to the associated skin spectrum. AN management depends on underlying conditions, and specific dermatological therapy is not generally required, unless the patient achieves metabolic control, has severe skin lesions, or desires cosmetic improvement. In IR cases, lifestyle interventions can help, including weight control up to bariatric surgery. In addition, metformin is a key player in the field of oral medication against DM type 2, a drug whose indication is extended to PCOS and even to AN itself, outside the specific panel of glucose anomalies. In terms of cosmetic intervention, limited data have been published on melatonin, urea cream, topical retinoids, vitamin D analogs, or alexandrite laser. In conclusion, awareness of IR and its associated clinical features is essential to provide prompt recognition of underlying conditions. AN represents a useful non-invasive surrogate marker of this spectrum in both children and adults. The pivotal role of this dermatosis could massively improve endocrine and metabolic assessments.

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“…Metabolic disorders caused by these mutations comprise hyperinsulinemia, mild hyperglycemia, and severe diabetes. Some patients with these defects may have nigricans acanthosis 25 . Women may exhibit male body traits and have cystic ovaries.…”

Section: Disorders Of the Insulin Functionmentioning

confidence: 99%

Predominant genetic mutations leading to or predisposing diabetes progress: A Review

Banoon

Alfathi

Mostafavi

et al. 2022

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Diabetes mellitus (DM) arises following poor capacity to generate or secrete insulin or insulin resistance; hence insulin production impairment creates the illness. Individuals can control their weight, impulsivity, blood pressure, and blood lipids at the commencement of the disease. A single genetic mutation affects nearly 3% of people with diabetes. Surprisingly, beta cell function is regulated by more than 20 genes. Benefits of genetic diagnosis include improved therapy, better prediction of illness prognosis and progression, genetic counseling, and possibly prevention. Alpha HNF1 mutations in the early stages may respond to the regimen. Still, most patients need it because they control their blood glucose and will be subject to microvascular or macrovascular complications. In cases where insulin does not control sugar, using low-dose sulfonylureas would be beneficial and lower four times the glucose metabolism of metformin. These patients are susceptible to sulfonylureas and may be treated for years in case of no blood glucose attack complications. The drug will start at one-fourth of the adult dose: MODY1. It is caused by a mutation in the alpha-HNF 4 gene and is relatively uncommon. The same is true, but the threshold for renal excretion is not low, and the incidence of upward alpha-HNF 4 mutations in cases where there is a robust clinical panel for alpha HNF 1 but not confirmed by genetic sequencing should be considered. The disease is also susceptible to sulfonylureas: MODY4 with a mutation in the MODY6 gene, IPF1, with a mutation in MODY7, NeuroD1 is characterized by a carboxy sterilise mutation, which is not common: MODY2. In children and adolescents, an increment in fasting blood glucose of 100 to 150 mg/dl is not typical. The incidence of this condition is usually considered to be type 1 or 2 diabetes, but a large percentage of the above patients are heterozygote individuals, the glucokinase mutations. Specific mutations, including those rare variants in WFS1 and ABCC8 genes, insulin receptor (IR), fructose 6-phosphate aminotransferase (GFPT2), and nitric oxide synthase (eNOS), as well as mouse pancreatic β‐cell lines (Min6 and SJ cells), showed that the HDAC4 variant (p. His227Arg) had been directly linked with T2DM. Keywords: type-2 diabetes, genetic mutations, risk factors

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Acanthosis Nigricans in Children and Adolescents with Type 1 Diabetes or Obesity: The Potential Interplay Role between Insulin Resistance and Excess Weight

Cited by 8 publications

References 36 publications

Insulin-resistance in paediatric age: Its magnitude and implications

Insulin-resistance in paediatric age: Its magnitude and implications

Acanthosis Nigricans: Pointer of Endocrine Entities

Predominant genetic mutations leading to or predisposing diabetes progress: A Review

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