title: Severe hypoglycemia and cardiovascular disease incidence in type 1 diabetes: the EURODIAB Prospective Complications Study.
abstract: OBJECTIVE
  Frequent episodes of severe hypoglycemia may increase the risk of cardiovascular disease (CVD) in people with diabetes. Our aim was to study the relationship between severe hypoglycemic episodes and CVD incidence in subjects with type 1 diabetes, and further, to assess if markers of inflammation/endothelial injury were enhanced in individuals who experienced hypoglycemic episodes.
  
  
  METHODS
  The prospective study included 2,181 type 1 diabetic patients from the EURODIAB Prospective Complications Study. At baseline, frequency of self-reported severe hypoglycemia, defined as episodes serious enough to require the help of another person, was assessed based on responses to a patient questionnaire. Both fatal/nonfatal CVD was assessed 7.3 years after baseline examination. At the follow-up visit, data on both severe and nonsevere hypoglycemic episodes in the previous year were collected through a questionnaire and markers of inflammation/stress response/endothelial injury measured by enzyme-linked immunosorbent assays in the 531 subjects of the nested case-control study, including 363 case subjects with one or more complications of diabetes and 168 control subjects with no evidence of any complication.
  
  
  RESULTS
  During the follow-up period, 176 patients had incident CVD. Logistic regression analysis showed that severe hypoglycemia at the baseline examination was not associated with incidence of CVD (adjusted odds ratios [95% CI]: one to two episodes, 0.87 [0.55-1.37]; three or more episodes, 1.09 [0.68-1.75]). Furthermore, follow-up serum levels of markers of endothelial damage/inflammation were not cross-sectionally associated with the frequency of hypoglycemic episodes.
  
  
  CONCLUSIONS
  Taken together our data do not support the hypothesis that in type 1 diabetes, severe hypoglycemia increases the risk of CVD.
authors.affiliation: Department of Internal Medicine, University of Turin, Turin, Italy. gabriella.gruden@unito.it
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gruden
authors.forename: Federica
authors.initials: F
authors.lastname: Barutta
authors.forename: Nish
authors.initials: N
authors.lastname: Chaturvedi
authors.forename: Casper
authors.initials: C
authors.lastname: Schalkwijk
authors.forename: Coen D
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Witte
authors.forename: John H
authors.initials: JH
authors.lastname: Fuller
authors.forename: Paolo Cavallo
authors.initials: PC
authors.lastname: Perin
authors.forename: Graziella
authors.initials: G
authors.lastname: Bruno
mesh_terms: D000293:Adolescent; D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000150:complications* / Q000453:epidemiology; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk