Repeated episodes of hypoglycemia as a potential aggravating factor for preclinical atherosclerosis in subjects with T1D

  1. Ignacio Conget, MD, PhD (iconget{at},2
  1. 1Endocrinology and Diabetes Unit, Hospital Clínic, Barcelona, Spain
  2. 2CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Barcelona, Spain
  3. 3Radiology Unit, Hospital Clínic, Barcelona, Spain
  4. 4Hemostasia Unit, Hospital Clínic, Barcelona, Spain
  5. 5Hormonal Unit, Hospital Clínic, Barcelona, Spain
  6. 6Cardiology Unit, Hospital Clínic, Barcelona, Spain


Objective- To evaluate through early preclinical atherosclerosis assessment whether repeated episodes of hypoglycemia represent an aggravating factor for macrovascular disease in type 1 diabetes (T1D).

Research Design and Methods- After sample-size calculation, a case-control study of 25 patients with T1D and repeated severe/non-severe hypoglycemia (H-Group) compared with 20 age/sex-matched T1D controls (C-Group) was designed. Assessment of preclinical atherosclerosis consisted of flow-mediated brachial dilatation (FMD) and carotid/femoral intima-media thickness (IMT) studies. To consider hypoglycemia awareness two different questionnaires and symptomatic response to an acute induction to hypoglycemia were performed. Evaluation of glycemic profile was obtained from continuous glucose monitoring. Endothelial function/inflammation markers were measured in euglycemia/hypoglycemia. A multivariate linear regression analysis was performed to test whether repeated hypoglycemia was independently associated with atherosclerosis.

Results- H- Group subjects displayed hypoglycemia unawareness and presented higher percentage of continuous glucose values and AUC<70mg/dl compared to C-Group (14.2±8.9 vs. 6.3±7.1%;p<0.02 and 2.4±1.8 vs. 0.6±1.0mg/dl/day,p<0.01). The percentage of maximal FMD was lower in H-Group than in C-Group (6.52±2.92 vs. 8.62±3.13%;p<0.05). A significantly higher IMT was observed at both carotid/femoral sites in H-Group (carotid, 0.53±0.09 vs. 0.47±0.08mm;p<0.05 and femoral, 0.51±0.17 vs. 0.39±0.09mm;p<0.05). Baseline inflammation/endothelial function markers were higher in the H-Group (leukocytes 7.0±1.8 vs. 5.6±1.4×103/ml; VWillebrand factor 119±29 vs. 93±26%; fibrinogen 2.82±0.64 vs. 2.29±0.44g/L; sICAM-1 408±224 vs. 296±95ng/ml;p<0.05 for all).

Conclusions- In addition to the induction of hypoglycemia unawareness and an increased risk for severe hypoglycemia, repeated hypoglycemia could be related to and considered an aggravating factor for preclinical atherosclerosis in T1D. The precise mechanisms explaining this association remains to be clarified.

  • Received July 16, 2010.
  • Accepted September 28, 2010.

This Article

  1. Diabetes Care
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