Nursing Pharmacology Chapter 29: Diabetes
Diabetes mellitus is the most important disease involving endocrine pancreas.
The severe form may be associated with ketosis if untreated.
Usually juvenile in onset, but occasionally adult onset.
Insulin nearly absent
Plasma glucagon elevated
Pancreatic B cell is not responsive to insulinogenic stimuli.
Exogenous insulin required to:
Reverse catabolic state
Infectious etiology possibly associated with a genetic predisposition.
Toxic environmental factor possibly also associated with a genetic predisposition.
Autoimmune response against pancreatic B cell antigens
Pancreatic B cell functional damage:
Destructive cytotoxins and antibodies from sensitized immunocytes
Autoimmune component suggested given that pancreatic B cell damage is reduced when immunosuppressive drugs e.g. cyclosporine/azathioprine, are administered early in Type I diabetes.
Pancreatic tissue transplanted from a nondiabetic monozygotic twins into the diabetic twin is rapidly destroyed in absence of immunosuppression.
Immune system mediation of pancreatic beta cell obstruction (Type I diabetes)
Associated with other autoimmune endocrinopathies:
Most patients have antibodies against insulin and other beta cell antigen.
Slow loss of insulin reserve
Islet cell tumor on a development (normal glucose; normal glucose tolerance; normal insulin response to glucose load)
Decreased glucose tolerance (fasting blood glucose: normal; last prediabetic phase)
Fasting hyperglycemia (no ketosis, even with poorly control diabetes)-- looks like NIDDM
Insulin-dependent stage -- ketoacidosis occurs, especially following stress (in this point life-long insulin therapy is required or pancreatic transplant)
Humoral and cell-mediated processes (cell-mediated mechanisms more important)
Islet cell antibodies: -- antibodies against:
Glutamic acid decarboxylase (two forms)
Ganglioside ganglioside antigens
Immune cell involvement:
Activated cytotoxic T lymphocytes (CD8+)
Releases cytokines (interleukin 1, tumor necrosis factor alpha, a.k.a., TNF-α.
By the time overt diabetes clinically presents, most insulin-producing cells have been destroyed.