title: Insulin therapy and hypoglycaemia: the size of the problem.
abstract: METHODS
  Hypoglycaemia is a fact of life for people with diabetes mellitus. Mild, asymptomatic episodes occur once or twice a week in insulin-treated diabetic subjects. Asymptomatic hypoglycaemia, including nocturnal hypoglycaemia, occurs in about 25% of diabetic subjects treated with insulin therapy. Mild hypoglycaemia, if recurrent, induces unawareness of hypoglycaemia and impairs glucose counterregulation, which in turn predisposes to severe hypoglycaemia. Even brief hypoglycaemia can cause profound dysfunction of the brain. Prolonged, severe hypoglycaemia can cause permanent neurological sequels. In addition, it is possible that hypoglycaemia may accelerate the vascular complications of diabetes by increasing platelet aggregation and/or fibrinogen formation. Finally, hypoglycaemia may be fatal. Hypoglycaemia induced by insulin as treatment of type 1 diabetes mellitus (T1 DM) is not the consequence of diabetes, but invariably of the non-physiological replacement of insulin.
  
  
  RESULTS
  A number of studies have demonstrated that by moving from non-physiological to more physiological models of insulin therapy, most of the hypoglycaemia problems may be overcome, the percentage of glycated hemoglobin (A1c) decreased, and the quality of life improved. Interestingly, in T1 DM with hypoglycaemia unawareness, prevention of hypoglycaemia reverses not only unawareness but also improves glucose counterregulation, primarily the responses of adrenaline.
  
  
  CONCLUSIONS
  In order to best prevent hypoglycaemia, insulin should preferably be given as continuous subcutaneous infusion via a minipump (the 'golden standard') or multiple daily insulin administrations with insulin analogues (basal insulin glargine, meal insulin rapid-acting insulin analogues) in T1 DM.
authors.affiliation: Section of Internal Medicine, University of Perugia, Italy. cgfanelli@interfree.it
authors.forename: Carmine G
authors.initials: CG
authors.lastname: Fanelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Porcellati
authors.forename: Simone
authors.initials: S
authors.lastname: Pampanelli
authors.forename: Geremia B
authors.initials: GB
authors.lastname: Bolli
mesh_terms: D001364:Awareness; D001921:Brain / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007328:Insulin / Q000009:adverse effects*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin