Diabetes mellitus
Type 1

Topic Completed: 1 August 2012

Minor changes: 13 July 2020

Copyright: 2002-2020,, Inc.

PubMed Search: IDDM[TI] OR insulin dependent diabetes mellitus[TI] pancreas[TI]

Deepali Jain, M.D.
Page views in 2019: 1,404
Page views in 2020 to date: 587
Cite this page: Jain D. Type 1. website. Accessed August 7th, 2020.
Definition / general
  • Presumed autoimmune cause for islet cell destruction but precise etiology unclear (Wikipedia: Diabetes Mellitus Type 1 [Accessed 8 December 2017])
  • Usually Northern European descent
  • 70% concordance in identical twins, HLA-D linked
  • Genetic predisposition may affect immune responsiveness to a beta cell autoantigen or method of presentation to T cells

Viruses and IDDM:
  • Viruses may damage beta cells, exposing antigens which trigger an autoimmune response
  • May be due to molecular mimicry (immune response develops against shared amino acid sequences): GAD and Coxsackie B4 virus share a six amino acid sequence
  • Retrovirus may serve as a superantigen

Autoimmune aspects:
  • Islet cell autoantibodies present in 70%; also CD8+ T cell infiltrate in islets
  • Antigens are glutamic acid decarboxylase (GAD), islet autoantigen 2, insulin associated antibody, gangliosides
  • GAD antibodies precede clinical symptoms, present in most newly diagnosed patients and 80% of first degree relatives
  • GAD antibody also causes stiff man syndrome, whose patients often have a history of IDDM
  • Many IDDM patients also have antithyroid peroxidase, antiparietal cell and antiadrenocortical antibodies
  • Some NIDDM patients have autoantibodies but no other features of IDDM
  • Usually chronic (years)
  • Clinical disease when 90% of islet cells are destroyed
Clinical features
  • Onset at age < 20 years, normal weight (unlike most NIDDM)
  • Characterized by PPP (polyuria, polydipsia, polyphagia) and ketoacidosis (DKA)
  • Polyphagia combined with weight loss is specific for IDDM; type 2 patients rarely have either
  • Severe fasting hypoglycemia is due to cessation of glycogen storage in fat and muscle
  • Glycosemia causes glycosuria with depletion of water and electrolytes
  • Also: low / absent plasma insulin, high plasma glucagon, unstable glucose tolerance (very sensitive to changes in insulin, diet, exercise, infection, stress), presence of free fatty acids (due to breakdown of adipose stores), which produces ketone bodies (acetoacetic acid and beta hydroxybutyric acid)
  • May get hyperosmotic nonketotic coma - dehydration due to hyperglycemic diuresis with failure to drink enough fluids to compensate, often in an elderly person with diabetes and stroke / infection
  • "Dead in bed syndrome": sudden death in young people with type 1 diabetes, cause unknown (Hum Pathol 2010;41:392)
Case reports
  • Immunosuppressive therapy is effective in children with new onset disease
Microscopic (histologic) description
  • Early insulinitis with marked islet atrophy and fibrosis and severe beta cell depletion (Islets 2011;3:131)
Microscopic (histologic) images

Images hosted on other servers:

Normal islets


2 year old girl with recent onset diabetes

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