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Increase in type 2 diabetes in children and adolescents in Western Australia.

OBJECTIVES: To document diagnosis rates of type 2 diabetes mellitus in children and adolescents in Western Australia over the past 12 years, the clinical characteristics of these patients and any comorbidities. DESIGN: Review of a prospectively recorded diabetes database. SETTING: Tertiary paediatric referral centre (the only such centre in WA). PATIENTS: All children and adolescents aged < 17 years diagnosed with type 2 diabetes between 1990 and 2002 and managed by Princess Margaret Hospital Diabetes Unit. MAIN OUTCOME MEASURES: Anthropometric and demographic data; glycohaemoglobin (HbA(1c)) level; blood pressure; lipid levels; presence of acanthosis nigricans. RESULTS: 43 patients (15 males and 28 females) were diagnosed with type 2 diabetes. Age (SD) at diagnosis was 13.6 (1.8) years. The rate of diagnosis has been progressively increasing (average annual increase in the unadjusted overall rates of type 2 diabetes was 27%). Twenty-three patients (53%) were of Indigenous origin and 18 (42%) resided in rural areas. The mean (SD) HbA(1c) level at diagnosis was 10.0% (3.2%). Seventy-two per cent of patients had acanthosis nigricans, 59% had hypertension, and 24% had hyperlipidaemia. CONCLUSIONS: There has been an increase in the diagnosis rate of type 2 diabetes in children and adolescents in WA. Comorbidities are frequent.

Acanthosis Nigricans↗

Alstrom syndrome in two siblings.

Alstrom syndrome is a very rare autosomal recessive inherited disorder. Only 50 cases have been reported since the syndrome was first described in 1959. This syndrome is characterized by obesity, impaired glucose tolerance with insulin resistance, retinal degeneration, neurosensory deafness, acanthosis nigricans, hepatic dysfunction, and some endocrine disorders. The index case of this report was a 12-year-old girl who became blind at the age of 6 years as the result of progressively impaired vision. At the age of 12, diabetes mellitus was diagnosed and acanthosis nigricans presented in the neck, axilla, and groin regions. Her 10-year-old brother had similar symptoms. Electroretinography and audiometry disclosed generalized pigmentary epithelial change, decreased to absent cone and rod responses, and moderate sensorineural hearing loss in both siblings. Biochemistry and oral glucose tolerance tests showed diabetes mellitus, dyslipidemia, and hepatic dysfunction in the index case. Elevations of insulin, C-peptide, and leptin concentrations were found in both siblings. Insulin resistance was also demonstrated in both siblings using the modified insulin suppression test with constant infusion of somatostatin and exogenous insulin.

Acanthosis Nigricans↗

[Correlation between menstruation disorders and insulin resistance].

UNLABELLED: The association between menstrual cylce abnormalities and insulin resistance in parallel to further clinical and biochemical findings was evaluated. MATERIAL AND METHODS: An observational, retrospective and transversal study was performed through a review of clinical charts of female patients (18-35 years old) who had undergone pelvic ultrasound seen at our service of Reproductive Biology in the Hospital Juárez de México form January 1996 to May 2002 with the following: abnormal menses (n = 22), eumenorrhea as controls (n = 28); without uterine or ovarian tumors, endocrine dysfunction or contraceptives. We assessed body mass index (BMI), waist hip ratio (WHR), ferriman, acanthosis nigricans, lipid profile and hormonal quantification. We used the HOMA procedure (18) for diagnosis of insulin resistance (glucose nmol/L (18 x insulin mIU/mL (22.5 = > 5.2. RESULTS: The abnormal menstrual patterns found were opsomenorrhea (n = 34), opsoamenorrhea (n = 17), amenorrhea (n = 23), proiomenorrhea (n = 3) and eumenorrheic controls (n = 28). There were no differences in age and BMI. The frequency of insulin resistance found was: controls (35.7%), opsomenorrhea (41.17%), opsoamenorrhea (41.17%), amenorrhea (78.26%) and proiomenorrhea (0%); the group with amenorrhea was statistically significant (P < 0.002). Those patients with obesity found in our groups exhibited a highest percentage of insulin resistance (Pearson: 0.37). WHR bigger 0.85 prevailed among patients with insulin resistance (P = 0.039). The finding of polycystic ovary was prevalent among opsoamenorrhea and opsomenorrhea patients with insulin resistance. Hyperandrogenemia and polycystic ovaries showed a higher percentage in amenorrheic and opsomenorrheic females with insulin resistance (P = < 0.05). COMMENTS: The amenorrhea symptom had a significant correlation with insulin resistance and it was also associated to obesity, acanthosis and polycystic ovaries.

Acanthosis Nigricans↗

An overview of dermatological conditions commonly associated with the obese patient.

Obesity is a chronic disease that may lead to skin problems, including acanthosis nigricans, skin tags, hyperandrogenism, striae distensae, plantar hyperkeratosis, and candidal intertrigo. Although some conditions (eg, skin tags and striae distensae) may simply be annoying or present cosmetic issues, conditions such as acanthosis nigricans and hyperandrogenism may be indicative of systemic diseases. Obesity also may contribute to poor healing of acute and chronic wounds that develop in this population. Some of the most common obesity-related skin disorders and factors affecting wound healing are described with suggestions on how to address these issues. With the continuing increase in the incidence of obesity, investigation into the specific care needs of this population is needed. In clinical practice, measures to reduce friction and shear and improve devices to move the obese patient would enhance care provision. Studies of the incidence of dermatological problems and the best treatments for these conditions are warranted.

Acanthosis Nigricans↗

[Hyperinsulinism syndromes caused by insulin resistance].

Resistance to insulin consists in a decrease in insulin's biologic action and is manifested mainly by hyperinsulinism. Clinical investigation of insulin resistance states relies on specialized tests, performed both in vitro and in vivo. The hyperinsulinemic-euglycemic clamp is the reference method for quantifying insulin resistance and can differentiate decreased insulin sensitivity and decreased maximal capacity for glucose uptake. Glucose flux measurements, using glucose labelled with stable isotopes, distinguish hepatic and peripheral factors involved in insulin resistance. In vitro studies include investigations for antibodies against insulin and insulin receptors, studies of insulin receptors and their tyrosine kinase activity, and studies of postreceptor cell metabolism. These investigations are especially useful in genetic syndromes of extreme insulin resistance, whose pathophysiology is largely unelucidated, including: insulin resistance syndromes with acanthosis nigricans, obesity-acanthosis nigricans-hyperandrogenism syndrome, lipoatrophic diabetes, leprechaunism, and other syndromes. But insulin resistance also plays a major role in non-insulin-dependent diabetes mellitus, insulin-dependent diabetes mellitus, and various pathological or even physiological endocrine alterations.

Acanthosis Nigricans↗

[Gastrointestinal carcinoma with skin diseases from the standpoint of surgery].

We encountered 21 patients with gastrointestinal carcinoma accompanied with skin diseases such as acanthosis nigricans, dermatomyositis, pemphigoid, erythrodermia, ichthyosis vulgaris, herpes zoster, Leser-Trélat's sign, Recklinghausen's disease and Gardner's syndrome. We have discussed such cases from the standpoint of surgery. There were 16 cases (76%) with gastric carcinoma, which were almost in the far advanced stage. Carcinomas of the other patients were seen in the esophagus, liver, pancreas, small intestine and rectum. Although skin lesions appeared before the onset of gastrointestinal symptoms in almost all cases, detection of carcinomas was very difficult until the symptoms emerged. In 6 of 21 patients (29%), carcinomas were detected by only skin manifestation, and they proved to be gastric cancer in all cases. Although the relationship of gastrointestinal carcinoma and skin diseases was unclear, we presented a 70-year-old woman with acanthosis nigricans accompanied with gastric cancer, whose skin manifestation was reduced by the therapy for gastric cancer. Therefore, some of these skin manifestation may be a symptom of the biological characteristics of the gastrointestinal carcinoma.

Acanthosis Nigricans↗

Hyperinsulinemia and hyperandrogenemia: in vivo androgen response to insulin infusion.

The plasma androgen responses to multiple-dose insulin infusions were determined in six normal females, four normal males, five obese females, and in three females with severe insulin resistance, hirsutism, and acanthosis nigricans. During the insulin infusions, the plasma glucose concentrations were maintained at 85 +/- 1 mg/dL by variable infusions of dextrose. Plasma androstenedione was augmented by 27-39% at physiologic insulin concentrations in the normal subjects and the obese group, and by 25% at hyperinsulinemic levels in the insulin-resistant group with acanthosis nigricans. The increased androstenedione concentrations achieved in the normal females and obese females were similar to the hyperandrogenemic levels seen in the acanthotic subjects in the basal state. Plasma cortisol also increased in all groups from 19% in normal females to 135% in obese females during the insulin infusions, but these changes did not reach statistical significance. These studies suggest that hyperinsulinemia may play a pathogenic role in the hyperandrogenemia of polycystic ovarian disease.

Acanthosis Nigricans↗

Tripe palms: a cutaneous marker of internal malignancy.

Tripe palms is a distinctive paraneoplastic cutaneous sign which is frequently associated with internal malignancy, specially carcinomas of the lung and stomach. We describe a patient with ovary carcinoma who showed a curious rugose thickening of the palms with accentuation of the normal dermatoglyphic ridges. The lesions were a specially prominent on the fingertips. The patient also showed classical acanthosis nigricans in the axillae and groin. The soles were spared. Histopathologic findings in palmar lesions consisted of an undulant epidermis, with hyperkeratosis, acanthosis, and papillomatosis. Excision of the ovary carcinoma was followed by complete regression of the cutaneous lesions. We review the literature about tripe palms and discuss the relationship between this striking cutaneous manifestation and internal malignancy.

Acanthosis Nigricans↗

[HAIR-AN syndrome].

Many clinical observations have suggested that there is a strong relationship between hyperinsulinemia and hyperandrogenism. HAIR-AN syndrome is defined as a constellation of hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN). Two major mechanisms could account for this syndrome: (i) hyperinsulinemia induced by insulin resistance causes hyperandrogenism, and (ii) hyperandrogenism causes insulin resistance and hyperinsulinemia. Acanthosis nigricans is considered to be an epiphenomenon caused by hyperinsulinemia. The causes of HAIR-AN syndrome include syndromes of extreme insulin resistance due to mutations in the insulin receptor gene, lipoatrophic diabetes, obesity, some endocrinopathies, and genetic and acquired ovarian hyperandrogenism.

Acanthosis Nigricans↗

Long-term survival in typical thanatophoric dysplasia type 1.

Thanatophoric dysplasia (TD), a severe skeletal dysplasia, is virtually always lethal neonatally, although a few previous reports have documented survival up to 4.75 years. We present a patient with survival beyond age 9 years and summarize his growth, development and medical history. The common Arg248Cys mutation in the extracellular region of fibroblast growth factor receptor 3 (FGFR3) was identified, eliminating the possibility that his long-term survival is attributable to an atypical mutation. This patient (and at least one other TD long-term survivor) have a rare skin disorder, acanthosis nigricans, which also occurs in Crouzon syndrome when caused by a FGFR3 mutation. Therefore, any molecular model of the origin of acanthosis nigricans secondary to FGFR3 mutations must account for the association of diverse mutations and these cutaneous effects.

Acanthosis Nigricans↗

Esophageal morphology from Linxian, China. Squamous histologic findings in 754 patients.

BACKGROUND: Linxian, China, has one of the highest rates of esophageal cancer in the world. Other authors have described high prevalences of histologic esophagitis, atrophy, and dysplasia in Linxian and have suggested that these findings may represent precancerous lesions in this population. In 1987, a new endoscopic survey allowed the authors to make an independent study of esophageal histology in Linxian. METHODS: There were 1567 satisfactory squamous esophageal biopsies available from 754 patients. These biopsies were classified as normal, atrophy, acanthosis, esophagitis, squamous dysplasia, or squamous cancer. RESULTS: Classified by their worst diagnosis, 56.5% of the 754 patients had normal mucosa, 0.0% atrophy, 11.5% acanthosis, 4.6% esophagitis, 22.7% squamous dysplasia, and 4.6% squamous cancer. CONCLUSIONS: The results show a different distribution of esophageal squamous diagnoses than has been reported previously from this population. The authors believe that the major reason for this discrepancy was differences in histologic criteria. In this survey, seemingly small differences in criteria could cause large differences in apparent disease prevalence; this was especially true for esophagitis. By the criteria used in this study, histologic esophagitis and atrophy are uncommon findings in Linxian, raising questions about their significance as precursor lesions of esophageal cancer in this population.

Biopsy↗

Heterogeneity for congenital generalized lipodystrophy in seventeen patients from Oman.

Seventeen children with congenital generalized lipodystrophy or Berardinelli-Seip Congenital Lipodystrophy (BSCL) from 12 consanguineous sibships were observed in Oman. All children had widespread absence of adipose tissue from infancy together with apparent muscle hypertrophy and hepatomegaly. They did not appear to represent a single homogenous entity, and it was possible to subclassify the cases into two distinct groups. In the first group of seven cases, the features were similar to other published cases with acanthosis nigricans, raised insulin levels, and insulin resistance. In this group, there was an association between the degree of acanthosis nigricans and the severity of the disorder. Molecular analysis of these cases showed homozygosity at the BSCL2 locus on chromosome 11q13 in four of the seven cases. In the second group of ten cases, there were striking abnormalities in both skeletal and nonskeletal muscle. Reduced exercise tolerance and percussion myoxedema were observed in skeletal muscle, while infantile hypertrophic pyloric stenosis, prominent veins (phlebomegaly), disturbance of cardiac rhythm, and cardiomyopathy were observed in nonskeletal muscle. There was evidence against homozygosity in some cases for the known loci for BSCL, and this group may represent a new clinical syndrome with lipodystrophy at a different genetic location.

Adolescent↗

Correlation of epithelial proliferation and squamous esophageal histology in 1185 biopsies from Linxian, China.

Epithelial proliferation is an active area of research in gastrointestinal cancer, but only a few studies have examined the relationship of esophageal epithelial proliferation and squamous histologic findings in populations with high rates of squamous esophageal cancer. In order to study this correlation, tritiated thymidine labeling was performed on 1185 esophageal biopsies from 745 residents of Linxian, China, a county with some of the highest esophageal-cancer rates in the world. Total labeling index (TLI = total labeled cells/total cells counted) was used to measure the amount of proliferation, and the proportion of labeled cells found in cell layers 4 to 10 (labeled cell fraction 4 plus, LF4+ = labeled cells in layers 4-10/total labeled cells) was used to measure the vertical distribution of proliferation. Of the biopsies, 979 were histologically normal, 51 showed acanthosis, 35 showed esophagitis, 116 showed squamous dysplasia, and 6 showed invasive squamous cancer. The mean values of both proliferation variables, stratified by histologic diagnosis, showed the following relationships: normal = acanthosis < esophagitis = dysplasia < cancer. The ranges of proliferation values overlapped extensively in all biopsy categories, so that measuring proliferation could not substitute for histologic diagnosis. It remains to be seen whether proliferation values, histologic diagnoses, or some combination of these methods is most predictive of subsequent esophageal cancer.

Adult↗

Dermatoses in 156 obese adults.

BACKGROUND: Skin diseases are mentioned as a frequent finding in the obese patient. However, to our knowledge no study has been done on this subject. OBJECTIVE: To determine the prevalence of skin diseases associated with different obesity grades and if any dermatosis can be considered an obesity marker. MATERIALS AND METHODS: A cross-sectional study of 156 obese patients who were 110% to 293% overweight were included. Complete medical history and dermatological examination were done. RESULTS: In the 126 female and 30 male obese patients, grades I to V, with a body mass index (BMI) of 27-51, cutaneous findings with statistical significance for linear trend were: plantar hyperkeratosis 54 patients p = 0.00001; acanthosis nigricans 46 patients p = 0.00005; striae 67 patients p = 0.03; skin tags 69 patients p = 0.01; keratosis pilaris 33 patients p = 0.007. Patients with plantar hyperkeratosis were distributed in the obesity groups as follows: grade I = 3 patients; grade II = 7 patients; grade III = 8 patients; grade IV = 17 patients; and grade V = 19 patients. Of the 76 diabetic patients, 26 had acanthosis nigricans, 38 had skin tags, and 27 had plantar hyperkeratosis. DISCUSSION: Plantar hyperkeratosis should be considered as a cutaneous stigma of severe obesity. This is probably a result of pressure directly related to the excess weight.

Adolescent↗

Toxicity of diethanolamine. 2. Drinking water and topical application exposures in B6C3F1 mice.

Toxicology studies of diethanolamine were conducted in male and female B6C3F1 mice to characterize and compare effects of exposure in the drinking water with those caused by topical application and to compare responses in mice to those observed in rats. Each study consisted of five dose groups plus controls and the size of each group was 10 animals per sex. Doses of diethanolamine ranged from 630 to 10,000 ppm in the drinking water study (approximately equivalent to daily doses of 100-1700 mg kg-1 in males and 140-1100 mg kg-1 in females) and from 80 to 1250 mg kg-1 in the topical application study. Exposure to diethanolamine caused dose-dependent toxic effects in the liver (hepatocellular cytological alterations and necrosis), kidney (nephropathy and tubular epithelial necrosis in males), heart (cardiac myocyte degeneration) and skin (site of application: ulceration, inflammation, hyperkeratosis, and acanthosis). Cytological alterations in the liver consisted of multiple hepatocyte changes, including enlarged cells that were frequently multinucleated, increased nuclear pleomorphism, increased eosinophilia and disruption of hepatic cords. A no-observed-adverse-effect level (NOAEL) was not achieved for hepatocellular cytological alterations or for acanthosis in the skin.

Administration, Oral↗

Topical iodine preparation as therapy against sulfur mustard-induced skin lesions.

Sulfur mustard (SM) is a powerful vesicant employed as an agent of chemical warfare. This study demonstrates the therapeutic effect of a novel topical iodine preparation as a postexposure treatment against SM-induced lesions in the fur-covered guinea-pig skin model. Iodine treatment 15 min after SM exposure resulted in statistically significant reductions of 48, 50, and 55% in dermal acute inflammation, hemorrhage, and necrosis, respectively, whereas, the epidermal healing markers, hyperkerathosis and acanthosis, were significantly elevated by 72 and 67%, respectively, 2 days after treatment. At the interval of 30 min between SM exposure and iodine treatment, there was a significant degree of healing or recovery, albeit to a lesser extent than that observed in the shorter interval. Although the epidermal healing markers were not elevated, the parameters indicative of active tissue damage, such as subepidermal microblisters, epidermal ulceration, dermal acute inflammation, hemorrhage, and necrosis, were significantly reduced by 35, 67, 43, 39, and 45%, respectively. At the 45-min interval between exposure and treatment, there was also a certain degree of healing or recovery expressed as significant reductions in dermal subacute inflammation, subepidermal microblister formation, and epidermal ulceration, whereas, acanthosis was statistically elevated, indicating an increased healing potential. At the 60-min interval, iodine was less efficacious; nevertheless, a significant reduction in the incidence of subepidermal microblisters and an expansion of the acanthotic area were observed. Gross ulceration was significantly decreased at intervals of 15 and 30 min between exposure and treatment. The local anesthetic, lidocaine, did not alter the therapeutic effect of iodine. SM was not affected chemically by iodine as measured by gas chromatography-mass spectrometry (GC-MS) analysis. These findings suggest that the iodine preparation functions as an antidote against skin lesions induced by SM.

Administration, Topical↗

Ultrastructural study of the skin in Sjögren-Larsson syndrome.

The ichthyosiform skin and the uninvolved skin of a 5-year-old Japanese female with Sjögren-Larsson syndrome were examined by light and electron microscopy to elucidate the keratinization disorder. Light microscopically, the epidermis of the ichthyosiform skin showed acanthosis, papillomatosis and hyperkeratosis. The horny cells had a basket-weave appearance. The granular cell layer was slightly thickened. Slight round cell infiltration and vascular dilatation were seen in the upper dermis. The uninvolved skin was histologically normal. Electron microscopically, in both ichthyosiform and uninvolved skin, abnormal lamellar or membranous inclusions were present in the cytoplasm of horny cells of the epidermis. These inclusions appeared to be derived from some of the lamellar bodies and/or abnormal membranous structures found in the cytoplasm of spinous and granular cells. Mitochondria in the epidermal basal cells were more numerous in the ichthyosiform skin than in the uninvolved skin. These findings indicate that, whether the skin is involved or not, the epidermis of the patient with this disorder may always have a structural abnormality, which may be genetically determined. Local environmental factors may play a role in inducing the acanthosis and papillomatosis of the epidermis.

Child, Preschool↗

Human skin grafts on nude athymic mice: a light microscopic stereological study.

A morphometric procedure is presented, which allows quantitative information to be obtained from the epidermis at the light microscope level. The application of this procedure to human skin grafted to the nude mouse revealed acanthosis of the grafted epidermis compared to the original donor skin. All epidermal layers were thicker, but the increase in the granular layer was especially marked. The ratio of the basement membrane surface to the epithelial surface showed no significant change. A possible explanation for the acanthosis of the graft might be the higher mechanical stress on the nude mouse compared to the original site on the abdomen. This adaptation of the grafted epidermis does not limit the usefulness of this animal model for dermatological research, when it is assessed by objective methods, allowing statistical comparison as described here.

Animals↗