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Type A Vs Type B Insulin Resistance

Treatment Of Type B Insulin Resistance: A Novel Approach To Reduce Insulin Receptor Autoantibodies

Treatment Of Type B Insulin Resistance: A Novel Approach To Reduce Insulin Receptor Autoantibodies

Go to: Abstract Background: Type B insulin resistance belongs to a class of diseases caused by an autoantibody to a cell surface receptor. Blockade of insulin action results in hyperglycemia, hypercatabolism, severe acanthosis nigricans, and hyperandrogenism in women. This rare autoimmune disorder has been treated with various forms of immunosuppression with mixed success. Methods: We describe 14 patients with type B insulin resistance referred to the National Institutes of Health, adding to an existing cohort of 24 patients. This report focuses on seven patients who were treated with an intensive combination protocol of rituximab, cyclophosphamide, and pulse corticosteroids aimed at control of pathogenic autoantibody production. Hematological, metabolic, and endocrine parameters, including fasting glucose, glycated hemoglobin, insulin dose, lipids, and testosterone, were monitored before and after treatment. Results: All seven treated patients achieved remission, defined as amelioration of hyperglycemia, discontinuation of insulin therapy, and resolution of hyperandrogenism. Glycated hemoglobin has normalized in all seven treated patients. Remission was achieved on average in 8 months from initiation of treatment. The medication regimen was well tolerated, with no serious adverse events. Conclusions: In seven patients with type B insulin resistance, standardized treatment with rituximab, cyclophosphamide, and pulse steroids results in remission of the disease. Future studies will determine whether this treatment protocol can be applied to other autoantibody/cell surface receptor disease states. Continue reading >>

Insulin-resistance Syndrome Type A

Insulin-resistance Syndrome Type A

Disease definition Type A insulin-resistance syndrome belongs to the group of extreme insulin-resistance syndromes (which includes leprechaunism, the lipodystrophies, Rabson-Mendenhall syndrome and type B insulin resistance syndrome; see these terms) and is characterized by the triad of hyperinsulinemia, acanthosis nigricans (skin lesions associated with insulin resistance), and signs of hyperandrogenism in females without lipodystrophy and who are not overweight. ORPHA:2297 Synonym(s): - Prevalence: Unknown Inheritance: Autosomal dominant or Autosomal recessive Age of onset: Childhood ICD-10: E13 UMLS: C0342278 C0342336 MeSH: - MedDRA: - Summary Epidemiology It is a rare disorder of unknown prevalence. Clinical description It is generally diagnosed in young women with marked signs of hyperandrogenism, but insulin resistance and acanthosis nigricans may be observed in men and in childhood. Acromegaloid facies or muscular cramps are sometimes associated. Hyperinsulinemia, a biological marker for insulin resistance, is often associated with glucose tolerance defects over the course of the disease, and diabetes progressively sets in. Hyperandrogenism (associated with polycystic ovarian syndrome (see this term) or ovarian hyperthecoses) leads to fertility problems. Etiology In some cases, the syndrome is caused by heterozygous mutations in the insulin receptor gene (INSR; 19p13.3-p13.2), affecting the region encoding the tyrosine kinase domain. Cases associated with homozygous mutations affecting the insulin-binding domain of the receptor have also been reported. However, only 15 to 20% of female patients with hyperandrogenism, insulin resistance and acanthosis nigricans present mutations in the insulin receptor gene. When such mutations are not found, the disease is of unk Continue reading >>

Association Of Type B Insulin Resistance And Type 1 Diabetes Resulting In Ketoacidosis

Association Of Type B Insulin Resistance And Type 1 Diabetes Resulting In Ketoacidosis

Type B insulin resistance (IR) is a rare autoimmune disease characterized by the presence of autoantibodies directed against the insulin receptor, resulting in a marked IR inducing hyperglycemia (1,2). We describe here what we believe to be a case of type 1 diabetes and ketoacidosis associated with type B IR syndrome. A 55-year-old Caucasian European man with mild obesity (BMI 32.4 kg/m2) was diagnosed as having type 2 diabetes. Insulin therapy was introduced after 3 years of oral antidiabetic therapy when weight loss suggested lack of insulin secretion. Four years after diagnosis, he developed a severe metabolic ketoacidosis. Continuous insulin infusion was promptly introduced, but ketones disappeared only after 6 days. Insulin requirement was exceptionally high (up to 5 units/kg/day for a 21.5 kg/m2 BMI) despite the use of a continuous subcutaneous insulin infusion associated with metformin. Clinically, there was neither acanthosis nigricans nor lipodystrophy. Antiglutamic acid decarboxylase 65 (anti-GAD) antibodies were positive on two dosages (3,335 and 3,418 cpm). Triglycerides level was 1.35 mM. Serum IGF-1 was 193 ng/mL (normal range, 55–186 ng/mL) and serum adiponectin was 7.4 μg/mL (normal range, 2.5–6 μg/mL). Soluble nuclear antigen–specific antibodies, antineutrophilic cytoplasmic antibodies, antinuclear antibody, anticardiolipin antibodies, serum assay for tumoral tracers, HIV, and viral hepatitis serologies were negative. Pelvic thoracoabdominal computed tomography was normal. Breath test, serologies, and research in feces of Helicobacter pylori were negative. Anti-insulin receptor autoantibodies, evaluated by their ability to compete with insulin for binding to its receptor in Chinese hamster ovary cells overexpressing the insulin receptor (3), wer Continue reading >>

Insulin Resistance: Definition And Clinical Spectrum

Insulin Resistance: Definition And Clinical Spectrum

INTRODUCTION Insulin resistance can be broadly defined as a subnormal biological response to normal insulin concentrations. By this definition, it may pertain to many biological actions of insulin in many tissues of the body. Typically, however, in clinical practice, insulin resistance refers to a state in which a given concentration of insulin is associated with a subnormal glucose response [1]. The term first came into use several years after the introduction of insulin therapy in 1922 to describe occasional diabetic patients who required increasingly large doses of insulin to control hyperglycemia. Most of these patients developed insulin resistance secondary to antibodies directed against the therapeutic insulin, which at that time was both impure and derived from non-human species [2]. Antiinsulin antibodies are rare in patients treated with recombinant human insulin, and the spectrum of clinical disorders in which insulin resistance plays a major role has changed markedly. Insulin resistance, rather than being a rare complication of the treatment of diabetes, is now recognized as a component of several disorders, including the following (table 1): Extreme insulin-resistance syndromes, such as the type B syndrome with autoantibodies against the insulin receptor [3], and rare inherited disorders, such as Leprechaunism with insulin-receptor mutations [4] and the lipodystrophic states [5]. Impaired glucose tolerance and type 2 diabetes mellitus. Obesity, stress, infection, uremia, acromegaly, glucocorticoid excess, and pregnancy, which cause secondary insulin resistance. Common disorders such as the metabolic syndrome, hypertension, hyperlipidemia, coronary artery disease, the polycystic ovary syndrome (PCOS), and ovarian hyperthecosis, in which the mechanism of the a Continue reading >>

Insulin-resistance Syndrome Type B

Insulin-resistance Syndrome Type B

Disease definition Type B insulin-resistance syndrome belongs to the group of extreme insulin-resistance syndromes (which includes leprechaunism, the lipodystrophies, Rabson-Mendenhall syndrome, and type A insulin resistance syndrome; see these terms) and occurs in the context of immune dysfunction. ORPHA:2298 Synonym(s): - Prevalence: Unknown Inheritance: Not applicable Age of onset: Adult ICD-10: E13 OMIM: - UMLS: C0342337 MeSH: - MedDRA: - Summary Epidemiology It is a rare disorder that affects middle-aged adults, predominantly females. Clinical description It may occur in the context of a well-characterized autoimmune disease (systemic lupus erythematosus; see this term), or suggest an immune disease (such as an elevated sedimentation rate, proteinuria, high levels of antinuclear antibodies or decreased levels of certain complement factors). The onset of the disease is usually marked with a rapidly progressive nonketotic and severely insulin-resistant diabetes, along with acanthosis nigricans (the typical skin lesion associated with insulin resistance) and hirsutism. Paradoxal hypoglycemia is sometimes observed and may be extremely severe. Etiology The syndrome is associated with the presence of serum auto-antibodies against the insulin receptor. Diagnostic methods The diagnosis is based on the clinical picture, results of laboratory tests, and on detection of anti-insulin receptor auto-antibodies in the serum. Management and treatment Treatment of the underlying autoimmune disease consists of non-specific immunosuppressors associated with very high doses of insulin to try to control the hyperglycemia. Prognosis Prognosis depends on the underlying autoimmune disease, but it is unfavorable in cases with hypoglycemia (leading to death in 50% of cases). Expert reviewer Continue reading >>

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