Microscopic acanthosis nigricans in type 2 diabetes.

Background: Acanthosis nigricans (AN) has been associated with insulin resistance. Individuals with type 2 diabetes are insulin-resistant and, therefore, could be expected to manifest AN. However, the prevalence and predictors of AN are unknown in this population. Objective: An outpatient population with Type 2 diabetes (DM) was compared with matched controls (C) for microscopic and clinical AN along with measurement of body habitus, insulin, glucose, and androgen levels. Methods: Twenty-four individuals with DM (12M, 12F) from a tertiary care center were compared with 24 C (12M, 12F). Fasting glucose, insulin, sex hormone binding globulin, androstenedione, dihydroepiandrosterone sulfate, and testosterone were measured. Height, weight, waist/hip measures, and a clinical survey for acanthosis were recorded. A 2-mm skin biopsy from midaxilla of the nondominant arm was taken for pathological review. Results: C and DM were matched for age and body mass index (BMI). Prevalence of microscopic AN in C was 12% (3/24) and in DM was 21% (5/24; NS). In C, AN was predicted by waist, waist/hip ratio, and fasting insulin measures, while none of the variables examined was predicative of AN in DM. Conclusions: Microscopic acanthosis nigricans was found in similar numbers of people with DM when compared with C. Fasting insulin levels most strongly predicted the presence of AN in C, while no significant predictors of AN were found in the population with DM.

This study examined the prevalence of both basal and glucose-stimulated hyperinsulinemia and acanthosis nigricans (AN) as well as the relationship between insulin and androgen levels in hyperandrogenic women. Sixty-two women who had an elevation of 1 or more plasma androgen levels were studied. The results in these women, grouped for analysis on the basis of obesity and ovulatory status, were compared to those in 36 control women of similar ages and weights. The anovulatory hyperandrogenic women had the clinical and biochemical features of the polycystic ovary syndrome (PCO). Oral glucose tolerance tests were performed with measurement of glucose, insulin, sex hormone-binding globulin (SHBG), and total and non-SHBG-bound sex steroid levels. AN was present in 29% of the hyperandrogenic women, the majority of them obese. Fifty percent of obese PCO women had AN, but they did not otherwise differ from PCO women lacking this dermatological change. Only women with PCO had significant hyperinsulinemia independent of obesity, and obese PCO women with AN had the highest serum insulin levels. Plasma glucose values during the oral glucose tolerance test were significantly increased in obese PCO women independent of the presence of AN, and 20% of these women had frank impairment of glucose tolerance. Ovulatory hyperandrogenic women had normal insulin levels and glucose tolerance. Obese and nonobese women had different relationships between sex steroid and insulin levels; obese women had significant correlations between insulin and non-SHBG testosterone levels (r = 0.30; P less than 0.05), whereas nonobese women had significant correlations between insulin and FSH (r = 0.40; P less than 0.01), dehydroepiandrosterone sulfate (r = 0.33; P less than 0.05), and SHBG (r = 0.37; P less than 0.05) levels, suggesting that the mechanisms underlying the association between sex steroid and insulin levels are complex. These findings suggest that 1) only women with PCO have hyperinsulinemia independent of obesity; hyperinsulinemia is not a feature of hyperandrogenic states in general; 2) AN is a common finding in obese hyperandrogenic women, particularly those with PCO; 3) only obese PCO women are at risk for impairment of glucose tolerance, independent of the presence of AN, suggesting that the negative impact of PCO and obesity on insulin action is additive; and 4) PCO women with AN can be considered as a subgroup of PCO and do not appear to have a distinct endocrine disorder.

Acanthosis nigricans (AN) is among the most common dermatologic manifestations of obesity and hyperinsulinism. In this study, we aimed to find the clinical and laboratory differences in obese children with AN and without AN (non-AN). In total, 160 obese children were included in the study. The duration of obesity, body mass index (BMI), BMI z-scores, birth weight, parental BMI, lipid profile, fasting and post-meal (PM) glucose and insulin levels were compared in 67 obese with AN and 93 obese without AN. Age was similar in both groups. AN group had higher male to female ratio (42/25 in AN, 43/50 in non-AN; P = 0.03), higher BMI (30.3 +/- 6.1 in AN, 26.4 +/- 3.6 in non-AN; P < 0.001) and weight for height (162.6 +/- 28.8 in AN, 144.6 +/- 15.8 in non-AN; P < 0.001) than non-AN group. There were no significant differences between the groups in birth weight, parental BMI and blood pressure. AN group had higher fasting (19.9 +/- 16.2 mU/L in AN, 10.4 +/- 7.6 mU/L in non-AN; P < 0.001) and PM insulin (88.6 +/- 87.3 mU/L in AN, 51.1 +/- 42.0 mU/L in non-AN; P = 0.01) and homeostasis model assessment for insulin resistance (HOMA-IR) (4.0 +/- 2.5 in AN, 2.2 +/- 1.8 in non-AN; P < 0.001) than non-AN group. However, fasting and PM glucose, triglyceride, low-density lipoprotein-, high-density lipoprotein- and total cholesterol levels were similar in both groups. BMI was correlated with HOMA-IR in both groups (r = 0.40 for AN, r = 0.28 for non-AN). PM glucose and PM insulin were correlated in both groups (r = 0.56 for AN, r = 0.39 for non-AN). However, fasting glucose and fasting insulin were correlated in only non-AN (r = 0.25), but not in AN group. Obese children with AN show higher insulin levels and HOMA-IR. AN is an important predictor of the insulin resistance in childhood obesity. Insulin secretory dynamics seem to be disrupted in fasting state initially, which is reflected as the loss of fasting insulin-glucose correlation in AN group.

Aim. To estimate (1) the prevalence of insulin resistance (IR) by fasting glucose: insulin ratio (G:I) (G:I ≤ 4.5) in overweight-obese polycystic ovary syndrome (PCOS) women, (2) to compare the clinical and biochemical parameters between insulin-resistant and insulin-sensitive groups.Materials and Methods. Eighty-one overweight-obese PCOS women (body mass index (BMI) ≥ 23 kg/m2) were studied. PCOS was diagnosed as per the Rotterdam 2003 criteria. BMI, abdominal circumference (AC), hirsutism (Ferriman Gallway score ≥6), presence of acne and acanthosis nigricans (AN) were noted in each case. Serum testosterone, sex hormone binding globulin (SHBG), fasting plasma glucose and insulin levels were measured.Results. 23.5% women were found to have IR. There were no differences in age, frequency of hirsutism, acne, serum testosterone and fasting glucose levels between insulin-resistant and insulin-sensitive women. However, there were significant differences in BMI, AC, frequency of AN, SHBG levels, fasting insulin levels and FAI between the two groups.Conclusion. PCOS women with IR are more obese; they have more upper body adiposity and AN. They are more hyperandrogenic. Simple clinical parameters will help to suspect IR in PCOS women.

Prevalence of Elevated Alanine Aminotransferase Among US Adolescents and Associated Factors: NHANES 1999–2004

Insulin Resistance and Adolescent Girls with Polycystic Ovary Syndrome

Abdominal fat distribution and insulin resistance in Indian women with polycystic ovarian syndrome

Objective: To find the correlation of the clinical and biochemical parameters in Indian adult women with PCOS with and without AN. Materials and Methods: 98 adult women (20-35years) with PCOS as per Rotterdam 2003 criteria were studied. Clinical parameters recorded - Body mass index (BMI), abdominal circumference (AC), blood pressure (BP), hirsutism score (modified Ferriman- Gallwey score m FG ≥ 6), presence of acne and acanthosis (AN). Transabdominal ultrasonography (USG) was done in each case. Hormonal parameters studied - Serum total testosterone (TT) level, sex hormone binding globulin (SHBG) level. Free androgen index (FAI) was calculated. Metabolic parameters studied – fasting plasma glucose (FG) and insulin (FI) levels. Glucose: insulin (G:I) ratio and HOMA (homeostasis model assessment) were calculated. Studied women were divided into two groups Group A: With acanthosis nigricans - 30 cases. Group B: Without acanthosis nigricans- 68 cases. Observations: Statistically significant differences between the means of groups with and without AN were found in the following variables - BMI (p value=0.0001); AC (p value=0.0001); SBP (p value=0.0001); DBP (p value= 0.01); FG (p value=0.12); SHBG (p value=0.0001); FAI (p value=0.0009); GI ratio (p value=0.0003) and HOMA (p value=0.0001). Bivariate positive Correlation with AN was observed between AC, BMI, SBP, DBP, Testosterone, FAI, and HOMA. Bivariate negative correlation with AN was observed with FG, SHBG and GI ratio. In terms of correlation coefficients, AN has the highest correlation with AC, followed by BMI and SHBG.

Acanthosis nigricans (AN) is a skin condition characterized by darkening and thickening of skin with formation of irregular folds, usually limited to a few specific areas of the body. Recently, AN has been reported to be linked to hyperinsulinemia and obesity. The aim of the present study was to determine whether or not the presence of AN in obese Japanese children is a reliable cutaneous marker. The authors analyzed the clinical characteristics of 439 obese Japanese children (260 boys, 179 girls; mean age 10.1 years; mean percentage overweight 51.9%), who had visited Tsuruoka City Shonai Hospital in 1990-2000. Eighty-two of the 439 children were examined using an oral glucose tolerance test (OGTT). Of these children, the authors retrospectively studied 16 subjects: eight with AN and eight without AN (age range: 10.8-13.9 years; percentage overweight range: 54.3-97.0%). They were age and percentage obesity-matched males with normal glucose tolerance during OGTT. Females with normal glucose tolerance during OGTT were excluded from the 16 subjects because the number was too small and children with impaired glucose tolerance or type 2 diabetes during OGTT were also excluded because of glucose toxicity. Eighty-two children including the 16 subjects were analyzed at their first visit for the presence or absence of AN on the posterior of the neck, and for characteristics including age, birthweight, body height, bodyweight, percentage overweight, blood pressure, liver function markers serum lipid concentrations, fasting plasma glucose concentrations and insulin concentrations shown by the results of OGTT. (1) Children with AN showed significantly more glucose intolerance including impaired glucose tolerance and type 2 diabetes compared with those children without AN, and fasting plasma insulin concentrations were most significantly correlated with the presence of AN. (2) Insulin resistance based on fasting plasma insulin concentrations was seen in significantly more children with AN than in children without AN, even in age and percentage obesity-matched subjects with normal glucose tolerance during OGTT. Acanthosis nigricans could be a reliable cutaneous marker of insulin resistance in obese Japanese children.

Comparative study of the therapeutic effects of oral pills containing desogestrel, cyproterone acetate and drospirenone, in patients with polycystic ovary syndrome (PCOS)

The prevalence of obesity and of type 2 diabetes mellitus in children have increased in the Chinese population over the past two decades, and thus diabetes prevention has become a major concern of public health agencies. Identification of individuals at risk for diabetes is an essential first step in designing and implementing intervention programs. Insulin resistance is the hallmark of the pathophysiology of type 2 diabetes mellitus. Subjects with hyperinsulinemia and impaired glucose tolerance are well accepted as being at high risk for diabetes. Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinemia has not been systematically evaluated in obese children. In order to further explore the relationship between obese childhood with benign acanthosis nigricans and insulin resistance and type 2 diabetes mellitus, we examined 19 obese children with benign acanthosis nigricans. Nineteen of seventy six obese children (25%) with BMI over 25 enrolled in the Children' Hospital of Zhejiang University School of Medicine fromJune 1st to September 1st in 2003 were studied. Skin biopsies were performed in these 19 obese children with acanthosis nigricans for final diagnosis. Levels of glucose, insulin, and glucose/insulin ratio were measured on fasting blood specimens and anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index were examined. Oral glucose tolerance tests were also performed in these 19 children with benign acanthosis nigricans. Anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index as well as fasting insulin level in acanthosis nigricans group were significantly higher than that of healthy controls (P < 0.01). Fasting glucose to insulin ratio (FGIR) of these 19 obese children with benign acanthosis nigricans was 4.27 +/- 0.53, indicating apparent insulin resistance. One of them was diagnosed as type 2 diabetes mellitus and ten of them showed impaired oral glucose tolerance. Childhood benign acanthosis nigricans is tightly associated with obesity, hyperinsulinemia, insuline resistance and type 2 diabetes mellitus, and may be used as a reliable index of insulin resistance.

The impact that dietary carbohydrates have on children developing type 2 diabetes remains controversial. Furthermore, there are limited pediatric longitudinal studies on changes in body mass index (BMI) and diet related to the development of acanthosis nigricans (AN), a risk factor associated with type 2 diabetes. Two 24 h dietary records were collected for 558 children, 2-8 years of age, at baseline and at a 2-year follow-up. Data on age, sex, BMI, and the presence of AN were also collected at each time point from the Children's Healthy Living Program. Logistic regression was used to determine factors associated with the presence of AN at follow-up. Multinominal regression was used to determine factors associated with changes in AN status. Linear regression was used to measure the associations between changes in dietary intake and in the Burke Score for AN. AN was present in 28 children at baseline and 34 children at follow-up. Adjusting for the presence of AN at baseline, age, sex, study group, baseline BMI, change in BMI z-score, time between assessments, and baseline intake, an increase from baseline for each teaspoon of sugar and serving of carbohydrate-rich food increased the risk for having AN at follow-up by 9% and 8%, respectively (p ≤ 0.05). An increased intake of added sugar (teaspoons) increased the risk of developing AN by 13% (p ≤ 0.01) and an increase in servings of foods rich in starch increased the risk of developing AN by 12% (p ≤ 0.01) compared to children who never had AN. Increasing the intake of fruit was also associated with decreased Burke Scores using multiple regression. However, the intake of energy and macronutrients were not associated with AN. Added sugar and foods rich in starch were independently associated with the occurrence of AN, suggesting the type of carbohydrates consumed is a factor in AN occurrence.

Prevalence of acanthosis nigricans and its association with hyperinsulinemia in New Mexico adolescents.

This study was designed to explore the association of insulin resistance and acanthosis nigricans (AN) in patients with polycystic ovary syndrome (PCOS). Fifty women, 18-37 years old, were included in the study, and divided into five groups consisting of: (I) 10 women with PCOS, abnormal body mass index (BMI) and AN; (II) 10 women with PCOS and abnormal BMI, but without AN; (III) 10 women with PCOS, normal BMI, and no AN; (IV) 10 women with abnormal BMI, but without PCOS or AN; and (V) 10 healthy women with normal BMI. Measurement of fasting glucose and insulin levels before and after oral glucose challenge was performed. Fasting serum insulin levels were found to be significantly lower in groups III, IV and V than in groups I and II, with no significant difference between groups I and II, or between groups III, IV and V. Total insulin response following administration of glucose did not differ significantly between the groups. These findings support the view that obese PCOS patients with AN do not have significantly higher insulin resistance than obese patients without AN. Insulin resistance is a necessary, but not the only, factor leading to the development of AN in patients with PCOS. Other factors should also be considered in the pathogenesis of this cutaneous reaction.

To establish the prevalence of insulin resistance and impaired glucose tolerance (IGT) and their determinants in a cohort of obese children and adolescents. A retrospective design was used. The study group included 234 patients with a body mass index (BMI) greater than the 95th percentile for age and gender and 22 patients with a BMI between the 85th and 95th percentile for age and gender referred for evaluation to a major tertiary-care center in Israel. Ages ranged from 5 to 22 y. Estimates of insulin resistance (homeostatic model assessment (HOMA-IR)); insulin sensitivity (ratio of fasting glucose (GF) to fasting insulin (IF) (GF/IF), the quantitative insulin sensitivity check index (QUICKI)), and pancreatic beta-cell function (HOMA-derived beta-cell function (HOMA %B)) were derived from fasting measurements. An oral glucose tolerance test (OGTT) was performed in 192 patients to determine the presence of IGT. Insulin resistance was detected in 81.2% of the patients, IGT in 13.5%, and silent diabetes in one adolescent girl. Only two patients with IGT also had impaired fasting glucose (IFG). The prevalence of IGT was higher in adolescents than prepubertal children (14.7 vs 8.6%). GF/IF and QUICKI decreased significantly during puberty (P<0.005), whereas HOMA-IR and HOMA %B did not. Insulin resistance and insulin sensitivity indexes were not associated with ethnicity, presence of acanthosis nigricans or family history of type 2 diabetes. Patients with obesity complications had lower insulin sensitivity indexes than those without (P=0.05). Compared with subjects with normal glucose tolerance (NGT), patients with IGT had significantly higher fasting blood glucose (85.9+/-6.5 vs 89.2+/-10.6 mg/dl, P<0.05), higher 2-h post-OGGT insulin levels (101.2+/-74.0 vs 207.6+/-129.7 microU/ml, P<0.001), a lower QUICKI (0.323+/-0.031 vs 0.309+/-0.022, P<0.05), and higher fasting triglyceride levels (117.4+/-53.1 vs 156.9+/-68.9, P=0.002). However, several of the fasting indexes except QUICKI failed to predict IGT. There was no difference between the group with IGT and the group with NGT in fasting insulin, HOMA-IR, HOMA %B or the male-to-female ratio, age, BMI-SDS, presence of acanthosis nigricans, ethnicity, and family history of type 2 diabetes. Insulin resistance is highly prevalent in obese children and adolescents. The onset of IGT is associated with the development of severe hyperinsulinemia as there are no predictive cutpoint values of insulin resistance or insulin sensitivity indexes for IGT, and neither fasting blood glucose nor insulin levels nor HOMA-IR or HOMA %B are effective screening tools; an OGTT is required in all subjects at high risk. Longitudinal studies are needed to identify the metabolic precursors and the natural history of the development of type 2 diabetes in these patients.