What is the pathophysiology of type 1 diabetes mellitus (DM)?

Updated: Jul 08, 2020
  • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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Type 1 diabetes mellitus is characterized by absolute insulin deficiency. In type 1A, a cellular-mediated autoimmune destruction of beta cells of the pancreas occurs. The disease process is initiated by an environmental factor—that is, an infectious or noninfectious agent in genetically susceptible individuals.

Some genes in the histocompatibility leukocyte antigen (HLA) system are thought to be crucial. A stress-induced epinephrine release, which inhibits insulin release (with resultant hyperglycemia), sometimes occurs and may be followed by a transient asymptomatic period known as "the honeymoon." Lasting weeks to months, the honeymoon precedes the onset of overt, permanent diabetes.

Amylin, a beta-cell hormone that is normally cosecreted with insulin in response to meals, is also completely deficient in persons with type 1 diabetes mellitus. Amylin exhibits several glucoregulatory effects that complement those of insulin in postprandial glucose regulation. Idiopathic forms of type 1 diabetes also occur, without evidence of autoimmunity or HLA association; this subset is termed type 1B diabetes.

The underlying pathophysiology of beta cell demise or dysfunction is currently more understood in type 1 diabetes than in type 2 diabetes. The rate of progression in type 1 diabetes is dependent on the age at first detection of antibody, number of antibodies, antibody specificity, and antibody titer. [1, 8] Three distinct stages of type 1 diabetes have been recognized. [1, 8] Both stages 1 and 2 are characterized by autoimmunity and a presymptomatic status; although there is still normoglycemia in stage 1, dysglycemia (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) is present in stage 2. Stage 3 is characterized by new-onset symptomatic hyperglycemia. [1, 8]

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