title: Early signs of atherosclerosis are associated with insulin resistance in non-obese adolescent and young adults with type 1 diabetes.
abstract: BACKGROUND
  Patients with type 1 diabetes have a substantial risk of developing cardiovascular complications early in life. We aimed to explore the role of insulin sensitivity (Si) as an early factor of atherosclerosis in young type 1 diabetes vs. non-diabetic subjects.
  
  
  METHODS
  Forty adolescent and young adult individuals (20 type 1 diabetics and 20 non-diabetics), age 14-20 years, without characteristics of the metabolic syndrome, participated in this cross-sectional study. After an overnight fast, Si was measured by hyperinsulinemic euglycemic clamp (40 mU/m2) and calculated by glucose infusion rate (GIR). Carotid intima-media thickness (cIMT) was measured in the common carotid artery with high-resolution ultrasonography. Risk factors of atherosclerosis (Body mass index [BMI], waist circumference, systolic blood pressure [sBP], triglycerides, low HDL-cholesterol and HbA1c) were also investigated.
  
  
  RESULTS
  cIMT was increased (0.52 ± 0.1 vs. 0.47 ± 0.1 mm, P < 0.01), whereas GIR was decreased (5.0 ± 2.1 vs. 7.1 ± 2.2 mg/kg/min, P < 0.01) in type 1 diabetics vs. non-diabetics. The differences in cIMT were negatively associated with Si (r = -0.4, P < 0.01) and positively associated with waist circumference (r = 0.34, P = 0.03), with no such associations between BMI (r = 0.15, P = 0.32), sBP (r = 0.09, P = 0.58), triglycerides (r = 0.07, P = 0.66), HDL-cholesterol (r = 0.10, P = 0.55) and HbA1c (r = 0.24, P = 0.13). In a multivariate regression model, between cIMT (dependent) and group (explanatory), only adjustment for Si affected the significance (ß = 0.08, P = 0.11) vs. (ß = 0.07, P < 0.01) for the whole model. No interaction between cIMT, groups and Si was observed.
  
  
  CONCLUSIONS
  cIMT is increased and associated with insulin resistance in adolescent, non-obese type 1 diabetic subjects. Although, no conclusions toward a causal relationship can be drawn from current findings, insulin resistance emerges as an important factor reflecting early signs of atherosclerosis in this small cohort.
authors.affiliation: Karolinska Institutet, Department of Clinical Science and Education, Sachs' Childrens' Hospital, Södersjukhuset AB, Stockholm, SE-118 83, Sweden. bjorn.rathsman@sodersjukhuset.se
authors.forename: Björn
authors.initials: B
authors.lastname: Rathsman
authors.forename: Stefan
authors.initials: S
authors.lastname: Rosfors
authors.forename: Ake
authors.initials: A
authors.lastname: Sjöholm
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D015992:Body Mass Index; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000473:pathology*; D059168:Carotid Intima-Media Thickness; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D042241:Early Diagnosis; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D055105:Waist Circumference; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008055:Lipids; C517652:hemoglobin A1c protein, human