c-peptide and Acanthosis-Nigricans

Concomitant confluent and reticulated papillomatosis (CRP) and acanthosis nigricans (AN) is rare. We present a case of concomitant CRP and obesity-associated AN in a 12-year-old obese Japanese girl. Curiously, oral minocycline therapy, which has been shown to be effective for CRP, was effective against both CRP and AN. Possible mechanisms by which minocycline could have improved skin lesions of CRP and obesity-associated AN are discussed. In addition, reports of concomitant CRP and obesity-associated AN are reviewed. CRP and obesity-associated AN share common clinicopathological features and some reports have described concomitant CRP and obesity-associated AN. Together with the observation that skin lesions of CRP and obesity-associated AN in the present case responded to oral minocycline therapy, these facts suggest a tight relationship or a common pathogenetic pathway between these pathologies.

Topics: Acanthosis Nigricans; Alkaline Phosphatase; Anti-Bacterial Agents; Biopsy; Blood Glucose; C-Peptide; Child; Female; Humans; Insulin Resistance; Minocycline; Obesity; Papilloma; Rare Diseases; Skin; Skin Neoplasms; Syndrome; Treatment Outcome

Fibroblast growth factor receptor 3 (FGFR3) gene mutations in the germline are well-known causes of skeletal syndromes. Somatic FGFR3 mutations have been found in malignant neoplasms and more recently in several cutaneous elements. We present a 14-year-old girl with mild hypochondroplasia who developed acanthosis nigricans. The report of a K650Q mutation in the FGFR3 gene in a similar case prompted us to conduct a point mutation analysis. The K650Q mutation was confirmed, but in contrast to the previous case, we additionally report findings of hyperinsulinemia. In the recent literature, an increasing number of different cutaneous elements have been found to harbor mutations of FGFR3, suggesting that FGFR3 plays a role in the pathogenesis of these elements. We review the present literature, describing studies in which FGFR3 mutations have been investigated in skin lesions: primarily seborrheic keratoses and epidermal nevi, but also other benign skin tumors and a single case of a squamous cell carcinoma. In addition, an overview of the FGFR3 point mutations in relation to each cutaneous element is given. Based on the current knowledge, it seems likely that these cutaneous lesions have a common genetic background. Our case shows that FGFR3 mutation analysis should be considered in case of the coexistence of acanthosis nigricans and a skeletal dysplasia. Testing for hyperinsulinemia is essential, also if a gene mutation is confirmed.

Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; C-Peptide; Dwarfism; Female; Gonadotropin-Releasing Hormone; Human Growth Hormone; Humans; Hyperinsulinism; Keratosis, Seborrheic; Metformin; Point Mutation; Receptor, Fibroblast Growth Factor, Type 3

Maturity-onset diabetes of the young (MODY) is often misdiagnosed as type 1/type 2 diabetes. We aimed to define patient characteristics to guide the decision to test for MODY in youth with diabetes.. Of 4750 patients enrolled in the Diabetes Registry at Texas Children's Hospital between July 2016 and July 2019, we selected ("Study Cohort", n = 350) those with: (1) diabetes diagnosis <25 years, (2) family history of diabetes in three consecutive generations, and (3) absent islet autoantibodies except for GAD65. We retrospectively studied their clinical and biochemical characteristics and available MODY testing results. Cluster analysis was then performed to identify the cluster with highest rate of MODY diagnosis.. Patients in the Study Cohort were 3.5 times more likely to have been diagnosed with MODY than in the overall Diabetes Registry (4.6% vs. 1.3%, p < 0.001). The cluster (n = 16) with the highest rate of clinician-diagnosed MODY (25%, n = 4/16) had the lowest age (10.9 ± 2.5 year), BMI-z score (0.5 ± 0.9), C-peptide level (1.5 ± 1.2 ng/ml) and acanthosis nigricans frequency (12.5%) at diabetes diagnosis (all p < 0.05). In this cluster, three out of five patients who underwent MODY genetic testing had a pathogenic variant.. Using a stepwise approach, we identified that younger age, lower BMI, lower C-peptide, and absence of acanthosis nigricans increase likelihood of MODY in racially/ethnically diverse children with diabetes who have a multigenerational family history of diabetes and negative islet autoantibodies, and can be used by clinicians to select patients for MODY testing.

Topics: Acanthosis Nigricans; Adolescent; Autoantibodies; C-Peptide; Child; Diabetes Mellitus, Type 2; Humans; Retrospective Studies

Islet immunity and beta cell reserve status were utilized to classify persons with ketoacidosis as the initial manifestation of diabetes. The clinical features of the various diabetes classes were also characterized.. Prospective cross sectional study.. Nelson Mandela Academic Hospital, Mthatha, Eastern Cape Province, South Africa.. Indigenous Black South Africans with ketoacidosis as the initial manifestation of diabetes.. Islet immunity and beta cell reserve were respectively assessed using serum anti-glutamic acid decarboxylase 65 (GAD) antibody and serum C-peptide after 1 mg of intravenous glucagon.. Serum anti-GAD 65 antibody > or = 5 units/L and < 5 units/L, respectively defined anti-GAD 65 positive (A+) and negative (A-). Replete (beta+) and deplete (beta-) beta cell reserve were serum C-peptide after glucagon injection of > or = 0.5 ng/mL and < 0.5 ng/mL, respectively. The proportions of patients with A+beta-, A+beta+, A-beta- and A-beta+ and their clinical characteristics were determined.. Of the 38 males and 33 females who participated in the study, patients were categorized in various classes: A-beta+, 46.5% (n=33/ 71); A-beta-, 26.8% (n=19/71); A+beta-, 22.5% (n=16/71); and A+beta+, 4.2% (n=3/71). The ages of the various classes were: 41.8 +/- 13.8 years for A-beta+ (n=33); 36.5 +/- 14.6 years for A-beta- (n=19); and 20.6 +/- 7.1 years for the combination of A+beta- with A+beta+ (n=19) (P<.0001, P<.0001 for the combination of A+beta- and A+beta+ vs A-beta+, P=.001 for the combination of A+beta- and A+beta+ vs A-beta-and P=.2 for A-beta- vs A-beta+. The clinical features of type 2 diabetes were most prevalent in A-beta+ class while the A+beta- and A+beta+ groups had the clinical profile of type 1A diabetes.. Most of the indigenous Black South African patients with ketoacidosis as the initial manifestation of diabetes had islet immunity, beta cell reserve status and clinical profiles of type 2 diabetes.

Topics: Acanthosis Nigricans; Adolescent; Adult; Aged; Autoantibodies; Black People; C-Peptide; Cross-Sectional Studies; Diabetic Ketoacidosis; Female; Glutamate Decarboxylase; Humans; Insulin-Secreting Cells; Islets of Langerhans; Male; Middle Aged; Prospective Studies; Seroepidemiologic Studies; South Africa; Young Adult

The incidence of type 2 diabetes mellitus (DM2) in children has increased worldwide and is commonly associated with overweight. Forty-four children with DM2 were studied by clinical histories, anthropometric measurements, and biochemical analysis. Homeostasis model assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were determined to evaluate insulin resistance. Only five patients presented normal body mass index (BMI); the remainder were overweight, and 76% had acanthosis nigricans. Laboratory results yielded hyperglycemia, elevated glycosylated hemoglobin, insulin and C-peptide. Elevated HOMA-IR and decreased QUICKI values suggest insulin resistance. No significant difference was found between sexes, although overweight in girls had more influence over blood pressure and lipid levels (p <0.05). Time from diagnosis and HOMA-IR yielded relevant values (p = 0.010). Laboratory results, QUICKI, and HOMA-IR values suggested that these patients present DM2 and decreased insulin sensitivity. We recommend prevention of overweight and sedentary life-style.

Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Child; Diabetes Mellitus, Type 2; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Lipids; Male; Mexico; Sex Factors

The strong relation between type 2 diabetes mellitus and obesity with acanthosis nigricans is widely concerned. This study investigated the pancreatic beta-cell function in obese children with acanthosis nigricans, so as to find out the role of insulin secretion and insulin resistance in obese children with acanthosis nigricans.. Thirty-five obese children with acanthosis nigricans (19 males and 16 females with mean age 12.8 +/- 1.5 years) were enrolled in this study. Thirty-eight obese children (21 boys and 17 girls with mean age 11.9 +/- 2.6 years) and 39 normal children (20 boys and 19 girls with mean age 11.2 +/- 2.2 years) were recruited as obese and normal control groups. The levels of serum fasting insulin, C-peptide, proinsulin and true insulin were measured in all the subjects. The ratios of proinsulin/insulin and proinsulin/C-peptide were calculated. Homeostasis model assessment was applied to assess the status of insulin resistance and basic function of pancreatic beta-cell.. The levels of fasting insulin, C-peptide proinsulin, true insulin, the ratios of proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin secretion index of obese children with acanthosis nigricans, obese control children and normal control children were: 18.5 (5.0-60.5) pmol/L, 12.4 (6.1-35.8) pmol/L and 5.1 (2.0-32.8) pmol/L; 3.9 (1.3-14.0) microg/L, 2.4 (1.1-4.0) microg/L and 1.1 (1.0-4.2) microg/L; 28.8 (9.9-64.2) pmol/L, 9.5 (2.2-34.5) pmol/L and 4.2 (2.0-16.0) pmol/L; 33.0 (6.2-66.0) pmol/L, 10.6 (4.8-29.4) pmol/L and 4.5 (1.3-30.1) pmol/L; 1.2 (0.4-8.9), 0.9 (0.2-1.9) and 0.8 (0.4-2.0); 6.9 (2.5-36.6), 4.7 (1.2-12.3) and 3.6 (1.2-9.6); 5.0 (0.8-14.1), 2.6 (1.3-8.1) and 1.2(0.4-6.9); 303.3 (52.2-1,163.8), 213.6 (84.6-572.0) and 51.1 (19.1-561.4). The levels of fasting insulin, C-peptide, proinsulin, true insulin, the ratios of proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin secretion index in obese children with acanthosis nigricans were significantly higher than those in obese children (P < 0.001) and normal children (P < 0.001).. Obese children with acanthosis nigricans had higher insulin resistance and pancreatic beta-cell dysfunction; acanthosis nigricans may be a skin sign of high risk of type 2 diabetes mellitus.

Topics: Acanthosis Nigricans; Adolescent; C-Peptide; Child; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Male; Obesity; Proinsulin

We report two black adolescent subjects who presented with diabetic ketoacidosis, but who lacked autoimmune markers and demonstrated clinical and biochemical characteristics more typical of Type 2 diabetes, including obesity, acanthosis nigricans, positive family history for Type 2 diabetes, and Type 2 diabetic dyslipidaemia. Subsequent to acute presentation, insulin was discontinued in both subjects and excellent glycaemic control was achieved with metformin therapy alone. Four months following acute presentation, both had adequate C-peptide responses to intravenous glucagon. Type 2 diabetes can present as diabetic ketoacidosis in obese adolescent subjects.

Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Metformin; Obesity

To determine prevalence estimates in order to monitor diabetes, particularly type 2 diabetes, in American Indian youth.. To explore the feasibility of developing a case definition using information from primary care records, all youth aged <20 years with an outpatient visit or hospitalization for diabetes were identified from the Billings Area Indian Health Service database in Montana and Wyoming from 1997 to 1999, and the medical records were reviewed. Classification for probable type 1 diabetes was based on age < or =5 years, weight per age < or =15th percentile at diagnosis, or positive results of islet cell antibody test. Classification for probable type 2 diabetes was based on weight per age > or =85th percentile or presence of acanthosis nigricans at diagnosis, elevated C-peptide or insulin, family history for type 2 diabetes, or use of oral hypoglycemic agents with or without insulin or absence of current treatment 1 year after diagnosis.. A total of 52 case subjects with diabetes were identified, 3 of whom had diabetes secondary to other conditions. Of the remaining 49 case subjects, 25 (51%) were categorized as having probable type 2 diabetes, 14 (29%) as having probable type 1 diabetes, and 10 (20%) could not be categorized because of missing or negative information. Prevalence estimates for diabetes of all types, type 1 diabetes, and type 2 diabetes were 2.3, 0.6, and 1.1, respectively, per 1,000 youth aged <20 years.. Our definitions may be useful for surveillance in primary care settings until further studies develop feasible case definitions for monitoring trends in diabetes among youth.

Topics: Acanthosis Nigricans; Adolescent; Adult; Autoantibodies; Body Weight; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Guidelines as Topic; Humans; Indians, North American; Inpatients; Insulin; Islets of Langerhans; Medical Records; Montana; Outpatients; Retrospective Studies; Wyoming

Type 2 diabetes mellitus has never previously been described in UK children, although an increasing incidence in childhood is recognized in international studies. The prevalence of obesity in UK children is increasing and is a recognized risk factor for the development of diabetes. The aim of this study was to identify and characterize children with Type 2 diabetes in the West Midlands and Leicester.. Children were identified by contacting paediatricians responsible for diabetes in five hospitals. Details were collected on demographics, mode of presentation, investigations and treatment on a standard proforma.. Eight girls were identified with Type 2 diabetes, aged 9-16 years and who were of Pakistani, Indian or Arabic origin. They were all overweight (percentage weight for height 141-209%) and had a family history of diabetes in at least two generations. They presented insidiously with hyperglycaemia and glycosuria without ketosis and five were asymptomatic. Islet cell antibodies measured in seven patients were negative. Four had acanthosis nigricans which is a cutaneous marker of insulin resistance and the other four had high plasma levels of insulin and/or C peptide. These patients are distinct from those with maturity-onset diabetes of the young (MODY). All were initially managed with dietary measures, seven have been treated with oral anti-diabetic agents of whom two have subsequently required insulin.. These are the first UK case reports of Type 2 diabetes in children. Paediatricians need to be aware of the risk of Type 2 diabetes developing in childhood in high-risk ethnic groups, particularly in association with obesity and a positive family history.

Topics: Acanthosis Nigricans; Adolescent; Body Mass Index; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Glycosuria; Humans; Hyperglycemia; Hypoglycemic Agents; India; Insulin; Insulin Resistance; Obesity; Pakistan; Saudi Arabia; United Kingdom

Topics: Acanthosis Nigricans; C-Peptide; Female; Humans; Hyperinsulinism; Insulin Resistance; Lupus Erythematosus, Systemic; Middle Aged; Syndrome

Topics: Acanthosis Nigricans; Aged; Aged, 80 and over; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Syndrome

A boy affected by severe obesity (kg 117, Body Mass Index 37 kg/m2) and acanthosis nigricans, was treated with octreotide for 150 days (50 micrograms x three daily subcutaneous administrations). Before treatment the patient showed an exaggerated insulin (IRI) and C-peptide (CPR) response to a standard meal with a lowering in after-meal CPR/IRI molar ratio. During octreotide treatment both IRI and CPR response was reduced but CPR/IRI molar ratio rised after meal indicating an increase in hepatic insulin removal. Body weight and acanthosis nigricans were sharply reduced during treatment and the reduction was still maintained six months after the cessation of therapy. Furthermore, IRI and CPR response, as well as the behaviour of CPR/IRI molar ratio, remained within normal range. In conclusion long-term octreotide treatment has been able to correct hyperinsulinemia and to reduce body weight and acanthosis nigricans.

Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Hormones; Humans; Hyperinsulinism; Insulin; Male; Obesity, Morbid; Octreotide

It has been suggested that recombinant human IGF-I (rhIGF-I) is a potential therapeutic agent in diabetes mellitus. It is known to have glucose-lowering effects in normal individuals, in patients with non-insulin-dependent diabetes (NIDDM) and in extreme insulin-resistant states. IGF-binding proteins (IGFBPs) have the potential to affect the biological activity of rhIGF-I. We have studied the effect of infused rhIGF-I on IGFBP-1 and IGFBP-3 in a patient with Mendenhall's syndrome, a rare insulin-resistant state. During an infusion of 20 mg rhIGF-I, glucose concentrations fell from 44.1 +/- 7.2 to 31.5 +/- 7.2 (S.E.M.) mmol/l (P = 0.001), and insulin and C-peptide levels fell from 920 +/- 62 to 542 +/- 45 mU/l (P = 0.008) and 5466 +/- 633 to 3071 +/- 297 pmol/l (P = 0.02) respectively. Significant lowering of phosphate, magnesium and alkaline phosphatase concentrations was also noted. IGF-I levels rose from 48 +/- 10.2 to 410 +/- 50.1 micrograms/l (P = 0.001), and those of IGF-II fell from 279.8 +/- 8.3 to 104.3 +/- 7.9 micrograms/l (P = 0.001). IGFBP-1 concentrations did not significantly change during the infusion but those of IGFBP-3 increased from 1655 +/- 127 to 2197 +/- 334 micrograms/l (P = 0.002), despite a significant fall in GH concentrations from 10.7 +/- 2.6 to 4.1 +/- 1.1 mU/l (P = 0.007), suggesting that IGFBP-3 regulation is also IGF-I-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; C-Peptide; Carrier Proteins; Diabetes Mellitus; Growth Disorders; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Syndrome

Beta cell hypersecretion is associated with the syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans. It is unknown whether concomitant alpha cell secretory dysfunction occurs in patients with this syndrome. The authors evaluated the gastroenteropancreatic hormones in four family members with varying degrees of the hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome. Gastroenteropancreatic hormones were measured during oral glucose tolerance test with and without subcutaneous octreotide injection. The study revealed that the administration of subcutaneous octreotide resulted in suppression of beta cell function (insulin and c-peptide) but had no effect or a delayed effect on alpha cell secretion (glucagon). Furthermore, the severity of glucagon abnormalities paralleled that of beta cell hypersecretion and the clinical and phenotypic manifestations of acanthosis nigricans in our four patients. We speculate that this alpha cell aberration could potentially be involved in the altered glucose homeostasis and perhaps the skin manifestations of this syndrome. Therefore, glucagon levels should be evaluated in the hormonal studies in patients with hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome.

Topics: Acanthosis Nigricans; Adolescent; Adult; C-Peptide; Child; Female; Glucagon; Glucose Tolerance Test; Hirsutism; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Islets of Langerhans; Male; Octreotide; Pancreas

To investigate the relative contribution of insulin and sex hormones in determining the abdominal pattern of fat distribution in premenopausal women, five groups of age-matched subjects were examined: Group 1 consisted of 14 normal weight eumenorrheic women (NO); Group 2 of 9 obese eumenorrheic women (OB); Group 3 of 14 normal weight hyperandrogenic women with polycystic ovary syndrome (NO-HA); Group 4 of 10 obese hyperandrogenic women with polycystic ovary syndrome (OB-HA) and, finally, Group 5 of 10 obese hyperandrogenic women with polycystic ovary syndrome and acanthosis nigricans (OB-HA-AN). Both the two normal weight groups and the three obese groups were matched for body mass index values. Sex hormone pattern showed significantly higher LH and testosterone levels in hyperandrogenic women with respect to NO and OB women but obese hyperandrogenic groups (OB-HA and OB-HA-AN) presented significantly lower LH concentrations than NO-HA. Fasting and glucose-stimulated insulin levels were significantly higher in OB than NO, in OB-HA and OB-HA-AN than in OB and NO-HA, and in OB-HA-AN than in OB-HA, without any significant difference between OB and NO-HA. Body fat distribution, expressed by the waist to hip ratio (WHR), showed progressively higher values (p less than 0.01) from NO to OB, NO-HA, OB-HA and, particularly, OB-HA-AN women. Determination coefficients r2 obtained from simple regression analysis showed that the sum of insulin values during the glucose tolerance test and testosterone levels had a more significant power in determining WHR variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Acanthosis Nigricans; Adipose Tissue; Adult; Androgens; Blood Glucose; Body Mass Index; C-Peptide; Fasting; Female; Glucose; Gonadal Steroid Hormones; Gonadotropins; Humans; Insulin; Male; Obesity; Polycystic Ovary Syndrome; Regression Analysis

Acanthosis nigricans (AN) with insulin resistance has been traditionally attributed to insulin receptor abnormalities. To further clarify the postbinding defects of in vivo insulin action in this state, we applied the euglycemic insulin clamp technique, combined with the glucose trace infusion method, to 26 subjects: 12 AN patients (eight normoglycemic and four hyperglycemic), eight obese, and eight lean control subjects. The normoglycemic AN group exhibited fasting hyperinsulinemia (666% of control), 160% elevated hepatic glucose production (HGP), 425% increased posthepatic insulin delivery rate, and only slightly reduced (19%) insulin clearance rates, compared with controls. Except for the latter, all these abnormalities were statistically significant (P less than .05), and could not be accounted for by body overweight. AN patients with diabetes mellitus (AN + DM) exhibited a further decreased insulin responsiveness (30%) and clearance (38%), together with a major increase in HGP (320%). All AN patients showed a significant right-shift in the insulin dose-response curve, indicating a decrease in insulin sensitivity. In conclusion, AN is characterized by increased basal rates of HGP, and peripheral insulin resistance, which can be partially attributed to postbinding defects. In AN + DM, a worsening of these abnormalities may be responsible for unmasking the existence of diabetes.

Topics: Acanthosis Nigricans; Adolescent; Adult; C-Peptide; Dose-Response Relationship, Drug; Feedback; Female; Glucose; Humans; Insulin; Insulin Resistance; Male; Middle Aged

It has long been known that acanthosis nigricans is accompanied by insulin resistance. In certain insulin-resistant states, including obesity, a more sluggish response to the insulin/insulin inhibition feedback normally present in pancreatic beta cells has been documented. Some have claimed a sort of beta-cell insulin resistance "parallel" to that of the peripheral tissues. The present study assesses the efficiency of the insulin/insulin feedback in acanthosis nigricans patients, measuring the inhibition of the production of C-peptide (the indicator of beta cell secretion) induced by the administration of exogenous insulin during glucose clamping. This was done in order to compare the roles of the peripheral tissues and the beta cells in producing the insulin resistance typical of acanthosis nigricans. The study using the glucose-insulin clamp technique was conducted on 4 Acanthosis Nigricans patients with normal glucose tolerance and 4 healthy controls, the drop in C-peptide levels after the administration of exogenous insulin being assessed in the course of both steady states. The results showed that the acanthosis nigricans patients retained a beta cell response to the exogenous insulin through their peripheral tissues presented a reduced sensitivity to insulin as revealed by the glucose-insulin clamp. It therefore seems reasonable to attribute the endocrine metabolic alteration found in Acanthosis Nigricans to a peripheral receptor and/or post receptor alteration rather than central alterations in the beta cells that have yet to be demonstrated. It is concluded that in acanthosis nigricans the peripheral insulin resistance is primarily independent phenomenon and not "parallel" to insulin/insulin feedback.

Topics: Acanthosis Nigricans; Adolescent; Adult; C-Peptide; Depression, Chemical; Feedback; Female; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Islets of Langerhans

A 16-year-old boy with persistent hyperglycaemia (approximately 16 mmol/l in the fasting state) and acanthosis nigricans had insulin resistance and received daily up to 2800 U of short-acting, soluble, highly purified porcine insulin. The number and affinity of insulin receptors were markedly decreased. No significant insulin binding to IgG could be detected. Immunoreactive insulin varied between 1344 and 2400 mU/l. Endogenous insulin secretion and proinsulin levels were grossly elevated in the fasting state (C-peptide 2.2-3.5 pmol/ml; proinsulin approximately 1 pmol/ml). After an oral glucose tolerance test and intravenous arginine infusion, B cell hypersecretion was confirmed. The molar ratio of C-peptide to immunoreactive insulin, normally approximately 7, was about 0.3, clearly indicating that most of the immunoreactive insulin was exogenous. The molar ratio of proinsulin to C-peptide, which is about 0.05 in fasting control subjects, was 0.23-0.45, clearly showing that too high a proportion of proinsulin was being secreted. This may indicate that the constant hyperstimulation of the B cell leads to reduced conversion of proinsulin to insulin. Immunoreactive glucagon levels were within normal limits fasting but were above normal after intravenous arginine infusion. Thus, in this case of diabetes with acanthosis nigricans, the severe insulin resistance, probably caused by a receptor defect, was associated with markedly increased B cell function.

Topics: Acanthosis Nigricans; Adolescent; Arginine; C-Peptide; Diabetes Complications; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin Resistance; Islets of Langerhans; Male; Proinsulin; Receptor, Insulin; Syndrome