title: Severe hypoglycemia and coronary artery calcification during the diabetes control and complications trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study.
abstract: OBJECTIVE
  Recently, major attention has been paid to the role of hypoglycemia as a cardiovascular risk factor. While EURODIAB-investigators concluded that severe hypoglycemia is not a cardiovascular risk factor in type 1 diabetes, other investigators found the opposite. The primary purpose of this study was to investigate the role of severe hypoglycemia in atherosclerosis during the DCCT- and EDIC-years with special attention to overall glycemic levels.
  
  
  METHODS
  The effect of severe hypoglycemic rates on coronary artery calcification (CAC) was evaluated for the entire cohort (n = 1205) and glycemic stratified cohorts (HbA1C < 7.5% [58 mmol/mol], HbA1C ≥ 7.5%).
  
  
  RESULTS
  The association between CAC and mean DCCT-hypoglycemia rate was stronger than the association between CAC and mean EDIC-hypoglycemia rate. Although the DCCT-severe hypoglycemia rate without HbA1C-stratification was not significantly associated with a CAC-score ≥ 100 Agatston units (p = 0.093), the interaction between above glycemic ranges and DCCT-hypoglycemic rate was significant (p < 0.05). A sub-analysis of patients belonging to the lower glycemic range (HbA1C < 7.5%), adjusted for baseline age, gender, baseline diabetes duration, baseline neuropathy, baseline albumin excretion rate, systolic blood pressure, LDL-cholesterol, smoking status, body mass index and DCCT-A1C, indicated significant (p = 0.02) associations between DCCT-severe hypoglycemia rate and CAC-score ≥ 100. One unit increase in the natural logarithm transformed DCCT-severe hypoglycemia rate increased the risk of having a CAC ≥ 100 by 30%.
  
  
  CONCLUSIONS
  Our results suggest a cumulative effect of hypoglycemic events on cardiovascular risk. They provide a possible link between above mentioned contradictory reports. Our findings support the relevance of personalizing glycemic goals in diabetes management beyond HbA1C.
authors.affiliation: Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV. Electronic address: faehrmann@marshall.edu.
authors.forename: Elke R
authors.initials: ER
authors.lastname: Fährmann
authors.affiliation: College of Science, Division of Mathematics and Applied Science, Marshall University, Huntington, WV.
authors.forename: Laura
authors.initials: L
authors.lastname: Adkins
authors.affiliation: College of Science, Division of Mathematics and Applied Science, Marshall University, Huntington, WV.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Loader
authors.affiliation: College of Information Technology and Engineering, Marshall University, Huntington, WV.
authors.forename: Hyoil
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.affiliation: Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine (Biostatistics), Marshall University, Huntington, WV.
authors.forename: James
authors.initials: J
authors.lastname: Denvir
authors.affiliation: Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV; VA Medical Center, Huntington, WV.
authors.forename: Henry K
authors.initials: HK
authors.lastname: Driscoll
mesh_terms: D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000453:epidemiology*; D001786:Blood Glucose / Q000378:metabolism; D002114:Calcinosis / Q000453:epidemiology*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology*; D048909:Diabetes Complications / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D019468:Disease Management; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000150:complications*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents
keywords: Cardiovascular disease; Coronary artery calcification; DCCT/EDIC-study; Severe hypoglycemia; Type 1 diabetes