Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans

Alternative Names

  • Insulin Receptor, Defect in, with Insulin-Resistant Diabetes Mellitus and Acanthosis Nigricans
  • Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans, Type A
  • IRAN, Type A
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Diabetes mellitus

OMIM Number

610549

Mode of Inheritance

Autosomal dominant, recessive

Gene Map Locus

19p13.2

Description

Insulin-resistant acanthosis nigricans, type A (IRAN, Type A) is a patch of velvety pigmented skin that arises in correlation with insulin-resistant diabetes mellitus. The clinical features include diabetes mellitus, acanthosis nigricans, and blackish, soft skin patches. Worldwide epidemiologic studies proposed that acanthosis nigricans is an effective marker for insulin resistance amongst obese subjects despite of the geographic location. Children of any ethnic group with a body mass index greater than the 98th percentile have a 62% prevalence of acanthosis nigricans, while the malignant acanthosis nigricans (benign form) has no tendency towards a specific ethnic group. IRAN, Type A affects both males and females equally. Lesions of benign acanthosis nigricans may occur at any age including at birth, though it is more common within adult population. Malignant acanthosis nigricans arises more frequently in elderly people; yet cases were described in children with Wilms tumor, gastric adenocarcinoma, and osteogenic sarcoma.

Molecular Genetics

Insulin-resistant diabetes mellitus with acanthosis nigricans can originate due to mutations in the insulin receptor gene (INSR). The insulin receptor precursor is cleaved post-translationally into two chains (alpha and beta) that are linked covalently following the withdrawal of the precursor signal peptide. Glucose uptake is stimulated through the binding of insulin to the insulin receptor (INSR). INSR gene was found to have two transcript variants encoding various isoforms; it has a tyrosine-protein kinase activity, consists of 1,382 amino acids, and has a molecular weight of 156,319 kDa.

Epidemiology in the Arab World

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Other Reports

Kuwait

[See: Somalia > Bushnaq and Shaltout, 1989].

Somalia

Bushnaq and Shaltout (1989) reported a 9 year old Somali girl with diabetes, who was found to suffer from numerous somatic anomalies and acanthosis nigricans upon physical examination. The patient underwent biochemical and hormonal examinations which demonstrated only glucose metabolism abnormality and upon treatment she was found to be insulin resistant, which made attaining normoglycemia unachievable.

United Arab Emirates

Lestringant et al., (2000) studied the association of Acanthosis nigricans, hyperinsulinemia, and hormonal levels in 92 female subjects with Acanthosis nigricans from the United Arab Emirates (age range 16-65 years). Of these 92 females, 36 subjects were considered to have diabetes mellitus (DM) and 56 were euglycemic. The analysis showed that in cases of family history of DM, HDL-cholesterol (mmol/l) and uric acid (mmol/l) levels were higher. Overall, DM subjects had significantly higher values for hormone levels of TSH, FSH, LH, progesterone, testosterone, cortisol, prolactin, (growth hormone) GH, and ferritin. One year later, Bener et al. (2001) conducted a similar matched case-control study involving 184 female subjects (92 females with A. nigricans and 92 females without A. nigricans); (age range 16-65 years). BMI, family history of DM, fasting, glucose, HDL-cholesterol (mmol/l), triglycerides (mmol/l) and uric acid (mmol/l) levels were statistically significantly higher in obese women in acanthosis and non acanthosis groups. The results revealed that BMI, family history of DM, total cholesterol (mmol/l), triglycerides (mmol/l) and uric acid (mmol/l) levels were statistically significant higher in diabetic women in non-acanthosis. Furthermore, systolic blood pressure, total cholesterol (mmol/l), triglycerides (mmol/l) and uric acid (mmol/l) levels were statistically significantly higher in diabetic women in acanthosis groups. Overall, DM subjects had significantly higher values for hormone levels of TSH, FSH, LH, progesterone, testosterone, cortisol, prolactin, GH, and ferritin.

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