Diabetes mellitus

Diabetes mellitus-general

Topic Completed: 1 August 2012

Minor changes: 22 October 2020

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PubMed Search: Diabetes mellitus[TI] pancreas[TI] free full text[sb]

Deepali Jain, M.D.
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Cite this page: Jain D. Diabetes mellitus-general. website. Accessed October 25th, 2021.
Definition / general
  • Destruction of islets due to drugs (steroids, thiazides, pentamidine), hemochromatosis ("bronze diabetes" due to hemosiderin deposition in pancreas), hereditary ceruloplasmin deficiency (Hum Pathol 1997;28:499), infections (congenital rubella, CMV, coxsackievirus [Arch Pathol Lab Med 1980;104:438], enteroviruses [Diabetologia 2004;47:225]), pancreatitis, surgery, tumors, endocrinopathies (pituitary, adrenal, pregnancy) or idiopathic
Type 1

  • 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)
Type 2 (NIDDM)
  • Also called adult onset, non insulin dependent diabetes mellitus / NIDDM, type 2
  • 80 - 90% of cases of diabetes (Wikipedia: Diabetes Mellitus Type 2 [Accessed 8 December 2017])
  • Usually > 30 years old, obese (80% of cases, abdominal obesity more important than subcutaneous obesity), normal or increased blood insulin, rare diabetic ketoacidosis, no anti-islet antibodies

  • Normal insulin secretion and plasma levels but loss of pulsatile, oscillating pattern of secretion
  • Also loss of rapid first phase of insulin secretion triggered by glucose
  • NO insulinitis is present

  • Mild / moderate insulin deficiency, may be due to beta cell damage
  • Beta cells may be "exhausted" due to chronic hyperglycemia and persistent beta cell stimulation

  • 37 amino acid peptide, normally produced by beta cells, packaged and cosecreted with insulin
  • In NIDDM patients, tends to accumulate outside beta cells and resembles amyloid

Clinical features
  • 90%+ concordance in twins, apparently due to multiple genetic polymorphisms (no HLA association)
  • Due to insulin resistance (associated with obesity and pregnancy) or derangement in beta cell secretion of insulin
  • Associated with amyloid deposits in islets (amyloid associated with basement membrane heparan sulfate proteoglycan, Arch Pathol Lab Med 1992;116:951) and pituitary (Arch Pathol Lab Med 1995;119:1055)
Maturity onset diabetes of the young
Diagrams / tables

Images hosted on other servers:

Single gene mutations
resulting in monogenic
diabetes / MODY

  • High fasting glucose or impaired glucose tolerance (without diabetes, oral glucose loads cause only slight rise in blood glucose due to brisk insulin response; with diabetes, blood glucose rises markedly for a sustained period)
Case reports
Microscopic (histologic) description
  • Type 1: inconsistent reduction in number and size of islets, uneven insulinitis (T lymphocytes)
  • Type 1: early insulinitis with marked islet atrophy and fibrosis and severe beta cell depletion (Islets 2011;3:131)
  • Type 2: subtle reduction in islet cell mass, amyloid replacement of islets due to amylin fibrils (also seen in aging nondiabetics); associated with marked fatty replacement
  • Type 2: amyloid in the islets of Langerhans is the uniform pathologic feature
  • Gestational diabetes: lower total insulin+ area due to smaller islets (Islets 2011;3:231)
  • Infants of diabetic mothers: islet cell hypertrophy / hyperplasia

Histopathology pancreas: type 2 diabetes mellitus

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