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Background: Acanthosis nigricans (AN) is a dermatologic skin condition that is often overlooked in its role as an indicator of underlying cardiovascular disorders. Recognizing the importance of AN beyond its cosmetic concerns is crucial for improving patient outcomes. Objective: Provide a review of AN and what every dermatologist should know of its underlying cardiovascular risk. Methods: A literature search through PubMed was performed. Terms used were "Acanthosis Nigricans," "hyperinsulinemia," "cardiovascular disease," "diabetes," "insulin resistance,". Further articles were found using source materials from included references. Inclusion criteria involved studies showing the association between AN and cardiovascular risks, with a specific focus on obesity and insulin resistance. Results: Acanthosis nigricans increases risks of obesity and insulin resistance as individuals with AN exhibited a 2.6-fold higher likelihood of insulin resistance, independent of other factors. Acanthosis nigricans surpassed other risk factors in classifying individuals at risk for type two diabetes and cardiovascular disease. Conclusions: Recognizing the association of AN with cardiovascular disease provides an opportunity for early intervention, focusing on weight management and underlying metabolic disorders to improve both cosmetic concerns and cardiovascular health. Dermatologists should consider AN as a signal that prompts referral for a thorough assessment for associated metabolic diseases.

Background/Aim: Obesity and related metabolic abnormalities in adults are associated with peripheral neuropathy. Acanthosis nigricans (AN) is associated with insulin resistance, fatty liver, hyperlipidemia and glucose intolerance, all of which are risk factors for neuropathy. The aim of this study was to investigate if obese adolescents with AN have evidence of small nerve fiber damage. Material and methods: Adolescents with obesity with and without AN underwent body composition analysis, assessment of vibration perception threshold (VPT), monofilament sensitivity and corneal confocal microscopy (CCM) to quantify corneal nerve fiber density (CNFD), branch density (CNBD), length (CNFL) and inferior whorl length (IWL). Results: Forty-six participants with obesity with (n = 31) and without (n = 15) AN aged 15(14–17) years were compared to 20 healthy controls aged 13(12–14) years. There was no difference in VPT, monofilament sensitivity and CCM measures between adolescents with obesity and controls. However, adolescents with AN had a significantly higher weight (P = 0.022), fat% (P = 0.029) and fat-muscle ratio (P = 0.012) with a lower CNFD (P = 0.045) compared to those with obesity without AN. Conclusion: Adolescents with obesity and acanthosis nigricans have a higher fat mass and small nerve fibre loss, indicative of a sub-clinical neuropathy. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies among reproductive women worldwide, contributing greatly on the incidence of female infertility and gynecological cancers. It is a complex health condition combining of multiple symptoms like androgen excess, uncontrolled weight gain, alopecia, hirsutism, etc. Conventionally PCOS was associated with obesity while it is often found among lean women nowadays, making the disease more critical to diagnose as well treatment. The disorder has an impact on several signal transduction pathways, including steroidogenesis, steroid hormone activity, gonadotrophin regulation, insulin secretion, energy balance, and chronic inflammation. Understanding the aetiology and pathophysiology of PCOS is difficult due to its multiple causes, which include environmental factors, intricate genetic predisposition, and epigenetic modifications. Despite research supporting the role of familial aggregations in PCOS outcomes, the inheritance pattern remains unknown. Henceforth, to reduce the burden of PCOS, it is inevitably important to diagnose at early ages as well as intervene through personalized medicine. With this brief background, it was imperative to elucidate the genetic architecture of PCOS considering BMI as an controlling factor. This study aims to investigate the genetic basis behind obesity-mediated PCOS, focusing on both obese and lean individuals. It uses a comprehensive bioinformatics methodology to depict pathways and functionality enrichment, allowing for cost-effective risk prediction and management. In the present research, the representative study participants (N = 2) were chosen from a cross-sectional epidemiological survey, based on their anthropometric parameters and confirmation of PCOS. Upon voluntary participation and written consent, biological fluids (whole blood and buccal swab) were taken from where DNA was extracted. The clinical-exome sequencing was performed by the Next-generation Illumina platform using the Twist Human Comprehensive Exome Kit. A comprehensive bioinformatics methodology was employed to identify the most important, unique, and common genes. A total of 26,550 variants were identified in clinically important exomes from two samples, with 5170 common and 2232 and 2322 unique among PCOS lean and obese phenotypes, respectively. Only 262 and 94 variants were PCOS-specific in lean and obese PCOS. Three filters were applied to shortlist the most potent variants, with 4 unique variants in lean PCOS, 2 unique variants in obese PCOS, and 5 common variants in both. The study found that leptin signalling impairment and insulin resistance, as well as mutations in CYP1A1, CYP19A1, ESR1, AR, AMH, AdipoR1, NAMPT, NPY, PTEN, EGFR, and Akt, all play significant roles in PCOS in the studied group. Young women in West Bengal, India, are more likely to have co-occurring PCOS, which includes estrogen resistance, leptin receptor insufficiency, folate deficiency, T2DM, and acanthosis nigricans, with obesity being a common phenotypic expression. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Materials and Methods Results Conclusions Trial Registration This study examined the prevalence of oral signs and symptoms in paraneoplastic syndromes.A systematic search on oral paraneoplastic syndromes was conducted in MEDLINE/PubMed, Ovid, and Scopus databases from inception to April 1, 2024. Risk of bias was evaluated using the MURAD or Quality in Prognosis Studies tools, and a random‐effects meta‐analysis was performed. Evidence quality was rated using the GRADE approach.The study sample comprised 811 participants from 487 studies. Oral manifestations predominantly affected patients with paraneoplastic pemphigus, mucous membrane pemphigoid, and acanthosis nigricans. Palate is the most frequently affected site (18.2%; 95% confidence interval [CI] 14.7–21.9), while erosion was the most common lesion type (83.3%; 95% CI 72.2–92.0) associated with the underlying malignancy. The prevalence of death in people with paraneoplastic syndromes was 50.9% (95% CI 39.9–61.7), while the prevalence of remission after neoplasm treatment was 63.4% (95% CI 49.9–76.0). GRADE assessment revealed uniformly low to very low certainty for all outcomes studied.Further research is needed to understand the mechanisms behind these oral manifestations, which is crucial for earlier paraneoplastic syndrome diagnosis and optimal patient management.PROSPERO number: CRD42022328921 [ABSTRACT FROM AUTHOR]

Introduction: Almost all cases of malignant acanthosis nigricans with oral manifestations occurred in older age groups. Here, we report a case of malignant acanthosis nigricans in a young female presented with chief complaints of oral mucosal hyperplasia, who had previously been diagnosed with allergies. Case presentation: A 30-year-old female developed oral hyperplasia and rash following seafood consumption, with subsequent resolution of the rash but persistent oral lesions and the appearance of pigmentation on her hands, neck, and axillae. Clinical examination revealed papillomatosis, hyperemia, and velvety hyperplasia in the oral cavity. Biopsy results confirmed papillary hyperplasia. Despite the patient’s belief in good health, she was advised to undergo further systemic examinations. Elevated serum tumor markers and histologic analysis of an endoscopic biopsy confirmed gastric cancer with duodenal infiltration, leading to the diagnosis of malignant acanthosis nigricans. Unfortunately, the patient passed away due to heart failure during chemotherapy treatment. Conclusions: The majority of patients with malignant acanthosis nigricans present with oral lesions before the underlying malignancy is detected, emphasizing the importance of timely comprehensive systemic examination. Furthermore, our case suggests that age may not be a restrictive factor for the development of malignant acanthosis nigricans, and the presence of a rash can potentially obscure the cutaneous manifestations associated with this condition. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) share several pathophysiological mechanisms. While the prevalence of MASLD has been extensively studied in PCOS populations, the occurrence of PCOS among female adolescents with transient elastography (TE)-confirmed MASLD in pediatric hepatology settings remains poorly characterized. This cross-sectional study aims to address this knowledge gap and elucidate potential clinical and biochemical differences between female adolescents with MASLD and comorbid PCOS compared to those without PCOS. Methods: The study cohort included 45 female adolescents with TE-diagnosed MASLD. Comparative analyses of clinical and laboratory parameters were performed between those with (n = 19) and those without (n = 26) comorbid PCOS, diagnosed according to the Rotterdam criteria. Results: Adolescents with MASLD and comorbid PCOS exhibited significantly higher weight, lower height, and increased waist circumference compared to those without PCOS. Additionally, the prevalence of acanthosis nigricans was significantly higher in the PCOS group (68.4% versus 34.6%, p = 0.025). Regarding laboratory parameters, serum phosphorus levels and liver enzymes—including aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase—were significantly lower in adolescents with comorbid PCOS. However, no significant differences were observed in lipid profiles, glucose metabolism, or novel non-invasive biomarkers of MASLD. Conclusions: This study reveals distinct clinical and biochemical profiles in female adolescents with MASLD and comorbid PCOS compared to those without PCOS. These findings have the potential to inform and refine future screening protocols and diagnostic algorithms for these interrelated conditions, specifically tailored to pediatric hepatology settings. [ABSTRACT FROM AUTHOR]

Background: While insulin resistance and diabetes shine as the central stars in the constellation of obesity-related conditions, other common endocrine diseases are also closely associated with obesity and high body mass index. Main body: This review aims to illuminate the hormonal imbalances associated with obesity, beyond diabetes. It covers the prevalence, clinical presentation, screening, diagnosis, and treatment of some of these conditions. Conclusion: In obese patients, physicians must pay attention to hormonal disorders that may be associated with obesity. [ABSTRACT FROM AUTHOR]

Congenital skeletal disorders are a heterogeneous group of anomalies that become evident during gestation. They are expressed in the shape and growth of the bones during development because of a defective genetic background. With the follow‐up of pregnant women and the advances in prenatal ultrasonographic examination and molecular genetic tests, nowadays, congenital skeletal disorders are identified at an early gestational age. If they are considered lethal, the termination of pregnancy is advised. This work unveils an exceptional instance of a rare pathological condition identified in a perinate (birth ± 2 weeks) from the 17th to 19th centuries, recovered during an excavation at the cloister of the São Domingos Convent in Lisbon, Portugal. The skeleton presents with exuberant modifications that include, among others, severe shortening (micromelia) and bowing of the long bones of the upper and lower limbs. The main skeletal findings indicated a presumptive general diagnosis of skeletal dysplasia, while the differential diagnosis includes hypophosphatasia, campomelic dysplasia, achondrogenesis, thanatophoric dysplasia, and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) as the most plausible causes for the observed skeletal changes. Even though an exact diagnosis is unattainable based only on the macroscopic analysis of the bones, the phenotypic features observed in this perinate are more consistent with thanatophoric dysplasia type 1. [ABSTRACT FROM AUTHOR]

Background: Acanthosis nigricans (AN) is a common skin disease characterized by clear pigmented patches on the folds of the skin. However, the AN research field lacks scientific and comprehensive bibliometric analysis. This article aims to use bibliometric methods to summarize and visualize the distribution patterns, research hotspots, and development trends of AN literature. Methods: Literature from 1900 to 2024 was retrieved from the Web of Science Core Collection database through AN's thematic search. Using CiteSpace, VOSviewer, and Excel 2019, conduct a comprehensive analysis of the number of publications, countries/regions, institutions, authors, journals, highly cited literature, keywords, and so on, and sort out the hotspots and directions of AN. Results: From 1900 to 2024, 1675 publications were included in the bibliometric analysis, showing a steady annual increase in the number of publications. The United States leads in this research field, with the University of Texas System being a key research institution. The Journal of Clinical Endocrinology & Metabolism has the highest number of published papers. The most cited article is "Syndromes of Insulin Resistance and Acanthosis Nigricans: Insulin‐Receptor Disorders in Man" (1976). The author Taylor, SI, has published the most papers. "Acanthosis nigricans" is the most frequently occurring keyword. The main research hotspots and frontier areas in AN research are as follows: (1) The relationship between AN and other diseases is a popular research topic; (2) The connection between AN and insulin resistance (IR) is a current research focus; (3) Treatment of AN, with an emphasis on addressing the underlying causes and improving local skin conditions, represents the cutting edge of this field. Conclusion: This study summarizes the research trends and hotspots in the field of AN, offering valuable information and insights for scholars focused on AN scientific research, and providing a reference for future research directions. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1) agonists are a class of medications indicated for type 2 diabetes and obesity that may play a role in the management of cutaneous disease, in part due to their anti-inflammatory effects. These molecules interact with cytokines critical to the development and persistence of skin disease, such as TNF-α, IL-23, IL-17 and IL-22. Correspondingly, immunologic pathways that are downregulated by GLP-1 agonists may serve as a target for various skin conditions that are worsened by inflammation. Furthermore, the known benefit of weight loss for certain skin conditions may be further potentiated by GLP-1 agonists. In this brief report, the authors describe multiple cases of patients with psoriasis, hidradenitis suppurativa, acanthosis nigricans, and Hailey-Hailey disease for which patients experienced improvement subsequent to treatment with GLP-1 therapy. These cases demonstrate the utility of GLP-1 agonists in treating dermatologic conditions that are refractory to other therapies and further highlight the potential of GLP-1 agonists in treating skin disease. [ABSTRACT FROM AUTHOR]

Acanthosis nigricans (AN), with an estimated prevalence of 19.4% in the U.S., presents as hyperpigmented, velvety plaques in intertriginous regions. Acanthosis Nigricans negatively affects psychological well-being and particularly impacts skin of color individuals. Addressing the underlying cause of acanthosis nigricans, as current guidelines recommend, is often challenging. This highlights the importance of skin directed treatment for acanthosis nigricans. This systematic review evaluated topical, laser, and oral treatments for acanthosis nigricans and provides evidence-based recommendations for clinical use. Adhering to PRISMA guidelines, we evaluated 19 clinical trials investigating topical, oral, and laser interventions for acanthosis nigricans. Oxford Centre for Evidence-Based Medicine guidelines were used to make clinical recommendations. We strongly recommend topical tretinoin (grade A) and endorse the appropriate use of adapalene gel, urea cream, and fractional carbon dioxide laser therapy (grade B). Further research is essential to enhance our understanding of alternative treatments to determine additional evidence-based recommendations. This review aims to guide clinicians in managing acanthosis nigricans, especially when direct treatment of underlying conditions is impractical. [ABSTRACT FROM AUTHOR]

Objectives: Skin changes in acromegaly are often the first sign of the disease. The aim of this study was to describe the cutaneous findings in patients with acromegaly. In addition, a secondary aim was to investigate the possible association of these findings with remission status and concomitant endocrinopathies. Design, Patients, and Measurements: In this prospective multicenter study, 278 patients over the age of 18 years with acromegaly who were followed up in 14 different tertiary healthcare institutions were included. These patients, who were followed up by the Endocrinology Department, were then referred to a dermatologist for dermatological examination. The frequency of skin lesions was investigated by detailed dermatologic examination. Dermatological diagnosis is reached by clinical, dermatological and/or dermoscopic examination, and rarely skin punch biopsy examinations in suspicious cases. The possible association of the skin findings between remitted and nonremitted patients and with concomitant endocrinopathies were evaluated. Results: The most common skin findings in patients with acromegaly in our study were skin tags (52.5%), cherry angiomas (47.4%), seborrhoea (37%), varicose veins (33%), acneiform lesions (28.8%), hyperhidrosis (26.9%) and hypertrichosis (18.3%). Hypertrichosis was significantly more prevalent in patients nonremitted (p:.001), while xerosis cutis was significantly more prevalent in patients remitted (p:.001). The frequency of diabetes mellitus and hypothyroidism was significantly higher in patients with varicose veins and seborrhoeic keratosis than those without. Additionally, the coexistence of hypothyroidism, hyperthyroidism and galactorrhea was significantly higher in patients with Cherry angioma than in those without Cherry angioma (p‐values:.024,.034 and.027, respectively). The frequency of hypogonadism in those with xerosis cutis was significantly higher than in those without (p:.035). Conclusions: Cutaneous androgenization findings such as skin tag, seborrhoea, acne and acanthosis nigricans are common in patients with acromegaly. Clinicians should be aware that skin findings associated with insulin resistance may develop in these patients. It can be said that the remission state in acromegaly has no curative effect on cutaneous findings. Only patients in remission were less likely to have hypertrichosis. This may allow earlier review of the follow‐up and treatment of acromegaly patients presenting with complaints of hypertrichosis. Additionally, it can be said that patients with skin findings such as cherry angioma may be predisposed to a second endocrinopathy, especially hypothyroidism. Including dermatology in a multidisciplinary perspective in acromegaly patient management would be beneficial to detect cutaneous findings earlier. [ABSTRACT FROM AUTHOR]

Rabson–Mendenhall syndrome (RMS) is a genetic disorder with autosomal recessive inheritance caused by mutations in the insulin receptor (INSR) gene. It is characterized by severe insulin resistance, acanthosis nigricans, skin tags, and growth retardation. Management of this condition is challenging and requires multidisciplinary approach. We present a case report on RMS in a 7-year-old girl who presented with coarse facies, acanthosis nigricans, skin tags, short stature, abdominal distension, and hyperglycemia with hyperinsulinemia. Her genetic analysis revealed a mutation in exon 3 of the INSR gene. The patient is being treated with tablet metformin and is being followed up.

BACKGROUND: Acanthosis nigricans (AN), marked by velvety skin plaques, signifies an underlying systemic disorder linked to rising obesity and diabetes rates. This study explores a comprehensive investigation of current AN treatment options, aiding clinicians in choosing effective and appropriate interventions for patients. METHODS: A literature review was conducted using databases such as Google Scholar, PubMed, and MEDLINE, focusing on AN treatments in the last decade and totally 32 articles were evaluated. RESULTS: Topical treatments, including retinoids, vitamin D analogs, keratolytics, and peels, are explored. Topical retinoids, especially tretinoin and adapalene, have demonstrated efficacy in clinical studies, while vitamin D analogs like calcipotriol show promise. Systemic treatments, such as oral retinoids (isotretinoin, acitretin, etretinate), insulin sensitizers (metformin, rosiglitazone), and other oral medications, are discussed. Metformin stands out for its effectiveness in treating AN associated with insulin resistance (IR). Cosmetic lasers, including alexandrite and carbon dioxide (CO2) lasers, offer successful outcomes in treating AN although cost and availability can be limiting factors. Other treatments, such as podophyllin, fish oil, photochemotherapy (PUVA), and surgery, are also considered. CONCLUSION: AN necessitates a multifaceted approach, targeting both underlying systemic disorders and cosmetic concerns. The findings underscore the significance of topical treatments, systemic therapies like metformin, and the promising role of cosmetic lasers in AN management. Despite limitations in available studies, this comprehensive overview provides valuable insights for healthcare providers, emphasizing the need for personalized treatment strategies. As the prevalence of AN rises globally, continued research and clinical exploration are essential to refine and expand treatment options for this dermatological condition.

Background: Acanthosis nigricans (AN) is a dermatosis that manifests as asymptomatic and symmetrical darkening, affecting the skin of intertriginous areas. It is a marker of insulin resistance and is usually associated with metabolic syndrome (MS). The present study was conducted to study the morphological patterns of AN and to assess its correlation with different components of MS. Methodology: Using the purposive sampling technique (1-year period), 100 patients fulfilling the case definition of AN were enrolled based on the inclusion and exclusion criteria. A detailed history and a cutaneous examination (color, texture, and sites of AN) were done. Anthropometric measurements and scoring of the AN were done. Investigations were reviewed. Data were recorded, and MS was diagnosed using the National Cholesterol Education Program’s Adult Panel III criteria. The data were analyzed using Microsoft Excel 13 software. Results: The mean age was 36.9 ± 10.1 years, with a male-to-female ratio of 1:1.38. The mean duration of AN was 18.8 ± 12.5 months. Seventy percent of cases had involvement of two or more sites. MS was present in 55% of cases of AN. Gender, duration of AN, site of AN, neck and axilla severity, and total cholesterol were not statistically significantly associated with MS (P > 0.05). Its association with systolic and diastolic blood pressure, waist circumference, fasting blood sugar, and high triglyceride was found to be statistically significant (P < 0.05). A low high-density lipoprotein level was found to be highly significant (P < 0.01). On applying the Chi-square test, all five parameters of MS had a significant association with AN. Conclusion: Understanding the relationship between AN and MS is important, as patients with AN are at risk for all the components of MS individually and collectively.

Acanthosis nigricans (AN) is characterized by dark, velvety patches and thin plaques primarily in the body folds. AN is more prevalent in skin of color populations, including Black/African American, Native American, and Hispanic patients. As the U.S. population becomes increasingly diverse, the need for inclusive dermatologic research becomes more pressing. Given the increased prevalence of AN in skin of color patients, there is a need to evaluate representation in AN clinical trials. This study aims to uncover gender, race, ethnicity, and Fitzpatrick skin type (FST) representation in AN clinical trials. A systematic literature search was performed across PubMed, Embase, and Cochrane databases to identify participant characteristics in clinical trials focused on AN treatment. Our review yielded 21 clinical trials, totaling 575 participants, with an identified predominance of female participants (69.0%) and a surprising absence of race or ethnicity data. Out of the 11 studies that included FST data, 1.2% of participants were type II, 20.6% were type III, 50.0% were type IV, and 28.2% were type V. None of the participants were FST I or VI. Herein, we highlight a predominate inclusion of female and FST III-V patients in AN clinical trials, the populations most impacted by this condition. We also highlight the need for improved race and ethnicity reporting and the importance of including all FSTs in clinical studies. Addressing this gap is critical for developing safe, efficacious, patient-centered, and equitable treatments for all AN patients. Future research should prioritize comprehensive inclusion of race, ethnicity, and the full spectrum of FSTs. [ABSTRACT FROM AUTHOR]

Aims Rabson-Mendenhall syndrome (RMS) is a rare autosomal, recessive disorder characterized by severe insulin resistance due to mutations in the insulin receptor (INSR) gene. This study aims to analyze the clinical features and gene mutations in RMS, which have not been extensively studied. Methods PubMed, Embase, the China National Knowledge Infrastructure, and Wanfang were searched for "Rabson-Mendenhall syndrome" or "Black acanthosis hirsutism insulin resistance syndrome." Results A total of 42 cases from 33 articles were included. The body mass index ranged from 18.50 to 20.00 kg/m2 with an average of 16.00 kg/m2. There were no overweight (25.00∼29.90 kg/m2) or obese (≥30.00 kg/m2) patients. Acanthosis was present in 29 cases (29/42, 69.05%); growth retardation in 25 cases (25/42, 59.52%); dental anomalies including absence of teeth, crowding, and malocclusion in 23 cases (23/42, 54.76%); and hirsutism in 17 cases (17/42, 40.48%). The average glycosylated hemoglobin was 9.35%, and the average fasting blood-glucose was 8.44 mmol/L; the mean fasting insulin was 349.96 μIU/mL, and the average fasting C-peptide was 6.00 ng/mL. Diabetes was reported in 25 cases (25/33, 75.76%) all of which were diagnosed before 23 years old. All 42 patients had recorded gene mutations, with 22 patients (22/42, 52.38%) having ≥ 2 mutations and 20 cases (20/42, 47.62%) having only 1 mutation. No statistical differences were found in clinical features and laboratory parameters between patients with different mutations. Conclusion The study indicates that RMS should be considered in young patients with hyperinsulinemia, hyperglycemia with low weight, acanthosis nigricans, growth retardation, dental anomalies, and hirsutism. [ABSTRACT FROM AUTHOR]

This article discusses intertriginous skin disorders, which are common in general practice and can range from benign conditions to chronic diseases. These disorders occur in areas where opposing skin surfaces come into contact, such as the groin folds, axillae, and natal cleft. The article emphasizes the importance of a thorough history and physical examination in diagnosing these disorders and provides a list of common intertriginous skin disorders and their first-line management options. It suggests that referral to a dermatologist may be necessary in certain cases. Overall, the article concludes that most intertriginous skin disorders can be successfully managed in primary care. [Extracted from the article]

Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) is a bone dysplasia caused by a pathogenic variant of fibroblast growth factor receptor 3 (FGFR3). Pathogenic variants in FGFR3 also cause thanatophoric dysplasia (TD) and achondroplasia. Although the findings of SADDAN and TD during the fetal and neonatal periods are similar, they differ in their long-term prognoses. We conducted FGFR3 analysis in one male patient because of the difficulty in differentiating SADDAN from TD during the neonatal period. We found that the patient had a pathogenic variant, p. Lys650Met, which was similar to that previously reported in patients with SADDAN. Reports on long-term survival in patient with SADDAN are scarce, and there have been no reports of treatment with GH. We administered GH therapy for a markedly short stature. After treatment, his height increased by 4 cm each year for 4 years, the frequency of hospitalizations due to respiratory failure decreased, and the health improved. FGFR3 analysis is useful for diagnosing SADDAN during the early neonatal period. GH therapy may have contributed to the patient's long-term survival. [ABSTRACT FROM AUTHOR]

Background: Acrochordons or skin tags are common benign skin growths. Several studies explored the relationship between obesity and metabolic syndrome in adults but remains unexplored in children. Methods: This was a single‐center retrospective cohort study of outpatient dermatology patients between 1 January 2000 to 1 January 2021. Children under 18 years old diagnosed with acrochordons using diagnostic codes International Classification of Diseases, 10th Revision (ICD‐10) L91.8 and 9th Revision (ICD‐9) 701.8 were included. We collected patient demographics, past medical history, laboratory values, vital signs, and physical exam. Body mass index (BMI) was calculated and stratified into categories based on the Center for Disease Control's BMI‐for‐Age Growth Charts. Metabolic syndrome was diagnosed when three of the five criteria were met. Data were propensity‐matched and compared with NHANES (National Health and Nutrition Examination Survey), which offered a generalizable sample to the US population. Results: Fifty‐five patients under 18 years old with a diagnosis of acrochordons were mostly Caucasian (76%) and female (64%). The mean BMI was 27.3, with 49.5% categorized as obese and 20% as overweight. The mean age of diagnosis was 10.1 years. Acrochordon predominantly appeared in the axilla. In our cohort, three patients (5.5%) met the criteria for metabolic syndrome. The prevalence of obesity (42% vs. 21%), type 2 diabetes mellitus (4.8% vs. 0.6%), hyperlipidemia (8.1% vs. 0%), and hypertension (1.6% vs. 0%) was greater in our cohort compared with NHANES. Conclusions: Like the adult population, acrochordons may serve as marker for metabolic disease in the pediatric population. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes Mellitus (DM) one of the most common chronic disease in Europe, can affect every part of the body including the skin. Metabolic changes during the progress of diabetes mellitus, influence the occurence of various dermatoses such as Acanthosis nigricans, Necrobiosis lipoidica diabeticorum, bullosis diabeticorum, eruptive xanthomatosis and diabetic dermopathy. On the other hand, there are allergic skin reactions as a consequence of insulin infusion, diabetic pills treatment and using diabetic devices like insulin pumps and glucose monitors that can improve patiens glycemic control and their quality of life. Aim of the study: The aim of our study is to present skin manifestations associated with diabetes mellitus patients. The importance of early detection skin changes and its significance are also analysed. Material and methods: We searched electronic databases, using keywords such as „Diabetes Mellitus", „ Skin dermatoses assosiated with diabetes mellitus „ and „Acanthosis Nigricans". Conclusions: Human skin is a reflection of the processes that take place in the body. The characteristc dermatoses that appear on it, can be a clue for the doctor and help him in the diagnostic process and proper control of diabetes. Technological progress has led to the develompent of specialized devices to control the glycemia of patients, however, this is often associated with the deterioration in the well-being of patients and the benefits of treatment, by reverse allergic skin reactions to contact with the equipment. [ABSTRACT FROM AUTHOR]

Background: Acanthosis nigricans is a non‐inflammatory skin pigmentary disorder characterized by a dark, velvety appearance, primarily observed in the neck and axillary areas. It is commonly associated with obesity, diabetes, and insulin resistance. Although the primary treatment is correcting the underlying disorders, many aesthetic modalities have been established to improve appearance owing to cosmetic concerns. Aims: We aimed to compare and investigate the effectiveness and side effects of tretinoin 0.05% and glycolic acid 70% in treating acanthosis nigricans lesions of the axillary and neck area. Methods: This single‐blinded, randomized trial recruited patients with neck or axillary involvement. Each patient was randomized to use cream tretinoin 0.05% every other night on one side, while the other side was treated with glycolic acid 70%, which was applied every 2 weeks at the clinic for four consecutive sessions. The study duration was 8 weeks, and patients were evaluated every 2 weeks based on their response to treatment, satisfaction, and side effects. Results: Thirty patients, including 14 with neck lesions and 16 with axillary lesions, were included. Tretinoin was significantly more effective for axillary lesions in terms of treatment response and patient satisfaction (p = 0.02 and p = 0.008, respectively). It was also shown that as the severity of the lesions increased, the response to treatment and patient satisfaction decreased, specifically when treating axillary lesions with glycolic acid (p = 0.02 and p = 0.03, respectively). Conclusion: Neither method was significantly effective for neck lesions. However, tretinoin 0.05% was shown to be more efficacious in treating axillary lesions of acanthosis nigricans, despite causing minimal side effects. [ABSTRACT FROM AUTHOR]

Crouzon Syndrome (CS) with Acanthosis Nigricans is a disorder characterised by the premature joining of certain bones of the skull {Craniosynostosis (CSO)} during development and a skin condition called Acanthosis Nigricans. Two cases of CSO with abnormal facies were referred to the present tertiary genetic centre. The first case was a one-year-three-month-old female with CSO, normal Intelligence Quotient (IQ) and normal limbs, clinically diagnosed as CS. The second case was a two-year-two-month-old male child with CSO, choanal atresia, hydrocephalus, normal limbs, post-surgical follow-up and suspected as a syndromic CSO. Both cases showed the presence of diffuse Acanthosis Nigricans and the final diagnosis was CS with Acanthosis Nigricans. This condition is distinct from classical CS due to its dermatological features, hydrocephalus, choanal atresia and impaired glucose values. CS with Acanthosis Nigricans (CAN) showed a specific mutation in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene, while Classical CS, in contrast, has a mutation in the FGFR 2 gene. Both of these cases were confirmed by molecular testing as CAN. This is a very rare condition in our population because of its peculiar clinical associations. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 10-year-old girl with gray-brown patches in the axillary and inguinal folds. The girl had been unsuccessfully treated with topical cream and oral medication for a presumed tinea infection. Further examination revealed gray-brown macules and patches in the affected areas, as well as perifollicular pigment deposits. Biopsies confirmed the diagnosis of lichen planus pigmentosus inversus (LPPI). LPPI is a rare variant of lichen planus characterized by asymptomatic or mildly itchy pigmented lesions in skin folds. Treatment options include topical corticosteroids or calcineurin inhibitors. [Extracted from the article]

This article discusses a rare variant of lichen planus called lichen planus pigmentosus inversus (LPPI). LPPI is characterized by hyperchromic macules in non-sun exposed areas, typically occurring bilaterally in the axillae and groin of Caucasian patients. However, the article presents a case of LPPI with unilateral distribution in an Indian woman. The article describes the clinical features, dermoscopic evaluation, and line-field confocal optical coherence tomography (LC-OCT) findings of the case. The histopathological examination confirmed the diagnosis of LPPI. The article also discusses the differential diagnosis, etiology, and the potential use of LC-OCT as a diagnostic tool for LPPI. [Extracted from the article]

Acne keloidalis nuchae (AKN) is a condition that involves chronic inflammation of the hair follicles on the occipital scalp and posterior neck that often progresses to keloid-like plaques. AKN has most commonly been reported to affect postpubertal males of African descent. The cause of AKN has not been definitively described; however, it is likely an inflammatory response to trauma or infection of the scalp. AKN is associated with chronic scalp folliculitis, hidradenitis suppurativa, folliculitis decalvans, acne mechanica, keratosis follicularis spinulosa decalvans, cutis verticis gyrata, metabolic syndrome, acanthosis nigricans, and hypothyroidism. Treatment for AKN begins with topicals, antibiotics, and intralesional steroid injections. Refractory cases are treated with laser and surgery. Isotretinoin, cryotherapy, phototherapy, electrosection, and radiotherapy have also been effective in treating AKN but are less commonly used. In this review, we describe the existing understanding of AKN with a focus on comorbid conditions and available treatment options. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the prevalence of prediabetes (PD), undiagnosed type 2 diabetes (T2D), metabolic syndrome (MetS), and insulin resistance (IR) as well as related risk factors in Mexican population from Guanajuato, Mexico. Materials and methods. We performed a cross-sectional study in the Mexican population from León, Guanajuato, Mexico. A clinical and metabolic evaluation was performed with an oral glucose test (OGTT); PD, undiagnosed T2D, MetS, and IR were identified according to international guidelines. Results. Of the 1 470 participants included, 32.9% had PD, 8.4% undiagnosed T2D, 48.1% MetS, and 55.7% IR. Main risk factors associated with T2D and PD were central obesity, overweight, acanthosis nigricans, family history of T2D and age. Conclusions. The prevalence of glucose abnormalities, MetS, and IR are high in the Mexican population, and this is related to the high frequency of multiple risk factors in our population. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on the psychological and quality of life of young obese patients with acanthosis nigricans (AN) and explore the mechanism. Methods: Clinical data of 52 young AN patients who underwent LSG surgery at Shanghai Tenth People's Hospital from January 2020 to December 2022 were retrospectively collected, and 50 healthy individuals were selected as the control group (CON). The Beck self-rating depression scale ⁃Ⅱ was used to evaluate the psychological status, and the Chinese version of SF-36 was used to evaluate the quality of life of the subjects. The anthropometries parameters, glucose metabolic indicators, lipid metabolism indicators, and C-reactive protein (CRP) levels of AN patients were evaluated and calculated before and 12 months after surgery, and compared before and after surgery. Correlation analysis was performed between depression and related metabolic indicators. Results: The scores of each dimension of quality of life assessment in the AN group before surgery were significantly lower than those in the CON group (P < 0.05), and the incidence of depression (63.5%) was significantly higher than that in the CON group (P < 0.001), with a significantly higher severity of depression than the CON group (P < 0.001). The levels of fasting insulin, insulin resistance, blood lipids and CRP of the AN group before surgery were significantly higher than those of the CON group (P < 0.05). Twelve months after surgery, as the weight of AN patients decreased, blood lipids and CRP levels significantly decreased, and their hyperinsulinemia and insulin resistance significantly improved. Meanwhile, the mental health score in the SF-36 scale of AN patients significantly increased, and the depression score and severity also significantly improved. Depression scores in patients were positively correlated with body mass index, insulin resistance, and CRP. Conclusion: Depression in AN patients is closely related to increased insulin resistance and inflammatory factors. LSG effectively improves depression and quality of life in AN patients by reducing weight, improving insulin resistance, and inflammation. [ABSTRACT FROM AUTHOR]

Facial acanthosis nigricans (FAN) is an increasingly discussed anatomical variation of acanthosis nigricans (AN). Its presentation as brown to black pigmentation with ill-defined blurred margins with varying degree of textural changes commonly over forehead, temporal, and malar regions of the face predominantly in dark-skinned individuals with a male predilection can be confused with other common facial melanoses. Its pathogenesis, clinical features, and management are in many ways similar to in the commonly described areas like neck and major flexural areas. Understanding of FAN has gained momentum in the past decade with studies highlighting its association with various metabolic abnormalities particularly insulin resistance and obesity. It is now being considered to be a cutaneous marker of metabolic syndrome. While there is uniformity in its clinical description, there appears to be scope for further in depth biochemical and histopathological studies to link the pigmentation, altered texture and microscopic changes in individuals presenting with FAN and hyperinsulinemia with or without other features of metabolic syndrome. It awaits a consensus on grading its severity and correlating it with histological features as patients often hesitate to be subjected to a biopsy of the face. This is a review of current literature pertaining to FAN. Newer clinical, dermoscopic, histopathological, and biochemical insights will help to understand this relatively new entity. [ABSTRACT FROM AUTHOR]

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We present the case of a young male patient (height, 158.1 cm [+3.3 standard deviation (SD)]; weight, 63.7 kg [body mass index, 25.5]) with diabetes mellitus and severe insulin resistance associated with a heterozygous pathogenic insulin receptor substrate 1 (IRS1) frameshift mutation. The patient also had severe acanthosis nigricans. Notably, the patient's father was undergoing treatment with high doses of insulin for diabetes mellitus, and had been experiencing angina pectoris. Laboratory data showed a fasting plasma glucose level of 88 mg/dL, hemoglobin A1C (HbA1c) of 7.4%, fasting insulin level of 43.1 µg/mL, and a homeostasis model assessment-insulin resistance (HOMA-IR) score of 9.36, indicating hyperinsulinism. Oral glucose tolerance test revealed a diabetic pattern and insulin hypersecretion. In addition, the patient had hyperlipidemia. Genetic studies revealed a heterozygous frameshift variant of IRS1 [NM_005544.3:c.1791dupG:p.(His598Alafs*13)] in the patient and his father, which can impair the binding and activation of phosphoinositide 3 (PI-3) kinase and defectively mediate the translocation of glucose transporter type 4 (GLUT4) in adipose tissues, possibly leading to glucose intolerance. Therefore, this variant may be disease causing. After confirming IRS1 mutation, metformin was administered, and physical exercise and dietary management were initiated; metformin was well tolerated, and optimal glycemic control was maintained. [ABSTRACT FROM AUTHOR]

Introduction: Facial pigmentation is a common presentation of patients attending dermatology out patient department (OPD) and is of great concern to patients. Facial pigmentation may be multifactorial and is only rarely diagnosed accurately by a detailed history and clinical examination. Pigmentary disorders cause psychological distress and negatively impact the quality of life of an individual. Aims and Objectives: (1) To study different dermoscopic patterns in facial melanosis. (2) To estimate the frequency of different dermoscopic patterns. Materials and Methods: Patients with facial hyperpigmentation attending the dermatology OPD were recruited after taking their written consent. A detailed history was taken to collect demographic data. Clinical examination and dermoscopy were done in all patients. Biopsy was done as and when required. Descriptive statistics has been used to describe the quantitative data. Qualitative data were presented as frequency and percentage for clinical and dermoscopic patterns. Results: The study included 100 patients with 15 different facial melanoses. The most common age group affected was 21-40 years in 53 (53%) cases. The female-to-male ratio was 1.63:1. Melasma was reported as the most common cause of facial melanosis constituting 49 (49%) of the total cases. Out of the total melasma cases, epidermal melasma constituted 22 (45%) cases, dermal melasma constituted four (4%) cases and mixed melasma constituted 23 (47%) cases. Other cases included were lichen planus pigmentosus (14; 14%), facial acanthosis nigricans (14; 14%), periorbital hyperpigmentation (7; 7%), post-inflammatory hyperpigmentation (4; 4%), exogenous ochronosis (2; 2%), lentigines (2; 2%), frictional melanosis (2;2%), and one case each of Becker's nevus, nevus of Ota, olanzapine-induced hyperpigmentation, Riehl's melanosis, macular amyloidosis, and tanning. Conclusions: Melasma was reported as the most common cause of facial melanosis. The most common dermoscopic feature was accentuated pseudopigment network. The study is beneficial in understanding the different clinical and dermoscopic patterns of facial melanosis, thus helping the physician to effectively manage the conditions and reduce the need of biopsy. Limitations: (1) A small sample size. (2) Histopathological correlation was not done in all cases. [ABSTRACT FROM AUTHOR]

Introduction: Acanthosis Nigricans (AN) is an acquired disorder of keratinization. It presents as hyperpigmentation, velvety texture of skin that can involve any part of the body including the face. Different topical, systemic therapies, or physical therapies including laser have been explored. However, there are not many randomized controlled studies for the majority of therapy alternatives besides lifestyle modifications and weight reduction. Objectives: The aim of this study was to compare the effectiveness of 15% trichloroacetic acid (TCA) and 35% glycolic acid (GA) peel for AN. Materials and Methods: Forty participants were included and randomized into two groups. In groups A and B, peeling with 15% TCA and 35% GA was done, respectively. The effectiveness of each peel was assessed using changes in the Acanthosis Nigricans Area and Severity Index Score (ANASI) and Physician Assessment Score. Statistical analysis included Wilcoxon-Mann-Whitney test, Friedman test, and generalized estimating equations. Results: The overall change in ANASI over time was compared in the two groups using the generalized estimating equations method. A significant difference was observed in the trend of ANASI over time between the two groups (P < 0.001). TCA peel group showed more change in ANASI as compared with GA peel group. Conclusion: In our research, 15% TCA has a better efficacy when compared with 35% GA peel after three sessions of chemical peeling. We therefore recommend the use of 15% TCA peel in AN as a safe and effective treatment option. However, more comprehensive randomized control studies are required for supporting data. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acanthosis nigricans is a common hyperpigmentation disorder with a profound aesthetic impact. The primary concern of most patients is the cosmetic improvement, that is way there is a continuous search for the most effective cosmetic therapeutic option. METHODS: 40 acanthosis nigricans patients were included, lesions are split into equal halves; right side treated with TCA 15% peel and left side was treated with microneedling followed by TCA 15% peel, both sides were treated monthly for three months. Response to treatment was assessed by acanthosis nigricans grade improvement along with the percentage of improvement in texture and pigmentation individually. RESULTS: There was statistically signiffcant improvement in acanthosis nigricans grade after treatment in both sides. The combination side showed more improvement in terms of texture and pigmentation. CONCLUSION: Both TCA 15% alone or combined with microneedling were effective in improving acanthosis nigricans with superior results in combination modality. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the frequency of different Skin Manifestations in people with type II Diabetes Mellitus who visit a tertiary care unit in Karachi, Pakistan. METHODOLOGY: This cross-sectional study was conducted at Liaquat College of Medical & Dentistry & Darul-Sehat Hospital Karachi from July to Nov 2023. A total of 200 patients with Type II Diabetes Mellitus, attending endocrine & dermatology OPD, were enrolled in this study by using consecutive, non -probability sampling techniques. Demographic parameters were noted. Data was analyzed by SPSS version 20. RESULTS: Two hundred type II Diabetes Mellitus patients (125 Females and 75 Males) were enrolled in the current study. The mean Age of the patients was 49.62± 10 years, and the mean duration of diabetes was between 6.74± 5.55 years. 115 out of 200 (57.5%) patients showed some skin manifestations. The skin manifestations observed were: Infections (bacterial/fungal) (17.38%), Ulcer & gangrene of foot (6.08%), Pruritis (13.33%), Diabetic dermopathy (10.42%), Foot swelling (7.81), Thick and scaly skin (8.68%), Pigmentation including shin spots (7.81%), Cellulitis (6.07%), Acanthosis nigricans (5.2%), Yellow nails (5.2%), Skin tags(3.46%), Psoriasis (3.46%). CONCLUSION: Participants having Diabetes Mellitus type II are found to have a high frequency of skin manifestations (57.5%). The ratio for females was higher than for males. The majority of participants had only one skin manifestation. A noteworthy association was found between higher HbA1c levels (8.1 to 14%) & the presence of cutaneous manifestations. [ABSTRACT FROM AUTHOR]

The article offers information on postadolescent acne in women, focusing on its causes and management. Topics include the continuation or development of acne in women beyond adolescence, potential underlying hormonal abnormalities, and the effectiveness of hormone therapy, including the combined oral contraceptive pill, in managing postadolescent acne.

Acanthosis nigricans (AN) is a skin condition characterized by hyperpigmentation and thickening, often found in individuals with insulin resistance. Despite this well-established association, the potential link between AN and hepatic fibrosis in people with type 2 diabetes (T2D) has yet to be thoroughly explored. We recruited a total of 300 people with T2D, half of whom had AN (n, 150), and the other half without AN (n, 150). We evaluated body composition, biochemistry, and hepatic fat analysis (using the controlled attenuation parameter, CAP), as well as assessments of hepatic stiffness (using the kilopascal, kPa) using Fibroscan. We used multivariable regression analysis to find independent predictors of AN and their relationship to hepatic fibrosis. Furthermore, we developed a prediction equation and AUC for hepatic fibrosis. Upon comparison between AN vs. NAN group, following were significatly higher; weight, BMI, hepatic transaminases, liver span, CAP, and kPa. After adjusting for age, weight, body mass index, diabetes duration, and specific anti-hyperglycaemic drugs (gliclazide, DPP-4 inhibitors, pioglitazone, and Glucagon-like peptide-1 receptor agonists), adjusted OR for AN were, liver span, 1.78 (95% CI: 0.91–3.49, p = 0.09), CAP, 7.55 (95% CI: 0.93–61.1, p = 0.05), and kPa, 2.47 (95% CI: 1.50–4.06, p = 0.001). A ROC analysis of predictive score for hepatic fibrosis showed optimal sensitivity and specificity at a score cut-off of 25.2 (sensitivity 62%, specificity 63%), with an AUC of 0.6452 (95% CI: 0.61235–0.76420). Acanthosis nigricans has the potential to be used as an easy-to-identify clinical marker for risk of hepatic fat and fibrosis in Asian Indians with T2D, allowing for early detection and management strategies. • T2D and AN showed higher values for weight, BMI, CAP, kPa, and liver span. • AN in people with T2D was independently associated with liver span, CAP and kPa. • AN as potential hepatic fibrosis risk marker in T2D Asian Indians. [ABSTRACT FROM AUTHOR]

Background: Women with type 1 diabetes depend on insulin injections throughout their life. However, the recommendation for strict metabolic control of diabetes requires the administration of supra-physiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis. Hyperandrogenism in women with type 1 diabetes may be associated with polycystic ovary syndrome (PCOS). This study was performed to investigate PCOS and its associated clinical symptoms and biochemical alterations in women with type 1 diabetes in the Palestinian Territories. This retrospective cohort study consists of 50 women with type 1 diabetes and 50 apparently healthy non-diabetic controls. Questionnaire interviews were conducted. The diagnosis of PCOS was based on chronic anovulation and biochemical evidence of hyperandrogenism. Serum total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and insulin were measured by ELISA. Results: The mean waist-to-hip ratio and age at menarche were significantly higher in diabetic women than in non-diabetic controls (81.9 ± 7.9 and 13.9 ± 1.6 years vs. 78.8 ± 5.7 and 13.2 ± 1.2 years, and P = 0.045, P = 0.020, respectively). Oligomenorrhea, acanthosis nigricans, seborrhea, and hirsutism were more frequent in diabetics. The levels of total testosterone and insulin were significantly higher in diabetics (0.58 ± 0.11 ng/ml and 15.8 ± 12.4 mlU/ml vs. 0.44 ± 0.11 ng/ml and 10.8 ± 4.5 mlU/ml, P < 0.001 and P = 0.010, respectively). PCOS was present in 11 (22.0%) of diabetic women compared to 3 (6.0%) in non-diabetics (P = 0.044). Diabetic women with PCOS received higher doses of insulin than non-PCOS women (72.7 ± 23.9 vs. 55.0 ± 19.8 UI.cc/ml/day, P = 0.023). PCOS women showed more frequent oligomenorrhea (100% vs. 15.4%, P < 0.001) and higher levels of total testosterone and insulin (0.64 ± 0.09 and 23.1 ± 13.0 vs. 0.53 ± 0.11 and 14.1 ± 11.8, P = 0.023 and P = 0.041, respectively). PCOS cases were significantly more frequent in diabetic women receiving intensive insulin therapy than their counterparts with non-intensive insulin therapy (40.9% vs. 7.1%, P = 0.012). Conclusion: Intensive insulin treatment in type 1 diabetes potentiates the development of PCOS and its related clinical and biochemical features particularly oligomenorrhea, hyperinsulinemia, and hyperandrogenemia. [ABSTRACT FROM AUTHOR]

Rabson–Mendenhall syndrome (RMS) is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We report the first case of RMS in a Paraguayan patient. The patient is a 6-year-old girl who presented with hypertrichosis, acanthosis nigricans, nephrocalcinosis, and elevated levels of glucose and insulin that served as diagnostic indicators for RMS. Genetic testing by next-generation sequencing (NGS) revealed two pathogenic variants in exons 2 and 19 of the INSR gene: c.332G>T (p.Gly111Val) and c.3485C>T (p.Ala1162Val), in combined heterozygosis. The novel INSR c. 332G>T variant leads to the substitution of glycine to valine at position 111 in the protein, and multiple in silico software programs predicted it as pathogenic. The c.3485C>T variant leads to the substitution of alanine to valine at position 1162 in the protein previously described for insulin resistance and RMS. The management of RMS is particularly challenging in children, and the use of metformin is often limited by its side effects. The patient was managed with nutritional measures due to the early age of onset. This report expands the knowledge of RMS to the Paraguayan population and adds a novel pathogenic variant to the existing literature. [ABSTRACT FROM AUTHOR]

Background: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment. Methods: CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records. Results: Data from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth–37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age. Conclusions: This analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this work was to describe the phenotype of adults presenting with a first episode of diabetic ketoacidosis (DKA) in Cape Town, South Africa, and identify predictors of insulin independence at 12 and 60 months after presentation. Methods: A prospective, descriptive cohort study of all individuals, 18 years or older, presenting for the first time with DKA to four public-sector hospitals of the Groote Schuur Academic Health Complex was performed. Clinical, biochemical and laboratory data including GAD antibody and C-peptide status were collected at baseline. Insulin was systematically weaned and stopped in individuals who achieved normoglycaemia within the months after DKA. Individuals were followed for 12 months and then annually until 5 years after initial presentation with ketoacidosis. Results: Eighty-eight individuals newly diagnosed with diabetes when presenting with DKA were included and followed for 5 years. The mean ± SD age was 35±10 years and the median (IQR) BMI at diagnosis was 28.5 (23.3–33.4) kg/m2. Overall, 46% were insulin independent 12 months after diagnosis and 26% remained insulin independent 5 years after presentation. Forty-one participants (47%) tested negative for anti-GAD and anti-IA-2 antibodies and had C-peptide levels >0.3 nmol/l; in this group, 68% were insulin independent at 12 months and 37% at 5 years after diagnosis. The presence of acanthosis nigricans was strongly associated with insulin independence (OR 27.1 [95% CI 7.2, 102.2]; p<0.001); a positive antibody status was associated with a lower likelihood of insulin independence at 12 months (OR 0.10 [95% CI 0.03, 0.36]; p<0.001). On multivariable analysis only acanthosis (OR 11.5 [95% CI 2.5, 53.2]; p=0.004) was predictive of insulin independence 5 years after diagnosis. Conclusions/interpretation: The predominant phenotype of adults presenting with a first episode of DKA in Cape Town, South Africa, was that of ketosis-prone type 2 diabetes. These individuals presented with obesity, acanthosis nigricans, negative antibodies and normal C-peptide and could potentially be weaned off insulin at follow-up. Classic type 1 diabetes (lower weight, antibody positivity, low or unrecordable C-peptide levels and long-term insulin dependence) was less common. The simple clinical sign of acanthosis nigricans is a strong predictor of insulin independence at 12 months and 5 years after initial presentation. [ABSTRACT FROM AUTHOR]