title: Impact of flexible insulin therapy on blood glucose variability, oxidative stress and inflammation in type 1 diabetic patients: the VARIAFIT study.
abstract: OBJECTIVE
  HbA1c only partially predicts vascular risk in patients with type 1 diabetes (T1D), and a role for blood glucose variability (BGV) is a matter of debate. For this reason, this study investigated the impact of an educational programme of flexible insulin therapy (FIT) on BGV and oxidative stress.
  
  
  METHODS
  Tests were conducted on 30 adult T1D patients in a prospective, single-centre trial at baseline (M0), and at 3 and 6 months (M3 and M6, respectively) of the FIT programme to determine BGV, as reflected by mean amplitude of glycaemic excursions (MAGE), low blood glucose index (LBGI), lability index (LI), average daily risk range (ADRR), glycaemic lability (scored by two diabetologists), urinary leukotriene E4 (LTE4), 11-dehydro-thromboxane B2 (TXB2) and 8-iso-prostaglandin F2α (PGF2).
  
  
  RESULTS
  HbA1c (7.7 ± 0.9%), ADRR, MAGE, LBGI and LI did not change from M0 to M3 and M6, although ADRR and LBGI significantly improved at M3 and M6 in patients with the highest baseline indices (≥ 40 and ≥ 5, respectively). TXB2 declined at M6 (832 ± 625 vs. 633 ± 972 pg/mg; P=0.048), whereas LTE4 and PGF2 remained stable. ADRR showed the strongest correlation with glycaemic lability scores at all visits (r≥0.84, P<0.0001).
  
  
  CONCLUSIONS
  A FIT educational programme improved BGV only in patients with the highest baseline variability, and led to no changes in HbA1c, while ADRR closely correlated with glycaemic lability score. Our data do not support a relationship between BGV and oxidative stress in T1D patients, although the impact of variability on TXB2 deserves further investigation (ClinicalTrials.gov NCT00973492).
authors.affiliation: Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, BP217X, 38043 Grenoble, France; Laboratory of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, 38043 Grenoble, France; HP2 laboratory INSERM U1042, Joseph Fourier University, Grenoble, France. Electronic address: PYBenhamou@chu-grenoble.fr.
authors.forename: P Y
authors.initials: PY
authors.lastname: Benhamou
authors.affiliation: Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, BP217X, 38043 Grenoble, France; Laboratory of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, 38043 Grenoble, France; HP2 laboratory INSERM U1042, Joseph Fourier University, Grenoble, France.
authors.forename: F
authors.initials: F
authors.lastname: Somers
authors.affiliation: Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, BP217X, 38043 Grenoble, France; Laboratory of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, 38043 Grenoble, France; HP2 laboratory INSERM U1042, Joseph Fourier University, Grenoble, France.
authors.forename: S
authors.initials: S
authors.lastname: Lablanche
authors.affiliation: Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, BP217X, 38043 Grenoble, France; Laboratory of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, 38043 Grenoble, France; HP2 laboratory INSERM U1042, Joseph Fourier University, Grenoble, France.
authors.forename: I
authors.initials: I
authors.lastname: Debaty
authors.affiliation: Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, BP217X, 38043 Grenoble, France; Laboratory of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, 38043 Grenoble, France; HP2 laboratory INSERM U1042, Joseph Fourier University, Grenoble, France.
authors.forename: A L
authors.initials: AL
authors.lastname: Borel
authors.affiliation: Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, BP217X, 38043 Grenoble, France; Laboratory of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, 38043 Grenoble, France; HP2 laboratory INSERM U1042, Joseph Fourier University, Grenoble, France.
authors.forename: L
authors.initials: L
authors.lastname: Nasse
authors.affiliation: Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, BP217X, 38043 Grenoble, France; Laboratory of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, 38043 Grenoble, France; HP2 laboratory INSERM U1042, Joseph Fourier University, Grenoble, France.
authors.forename: F
authors.initials: F
authors.lastname: Stanke-Labesque
authors.affiliation: Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, BP217X, 38043 Grenoble, France; Laboratory of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, 38043 Grenoble, France; HP2 laboratory INSERM U1042, Joseph Fourier University, Grenoble, France.
authors.forename: P
authors.initials: P
authors.lastname: Faure
authors.affiliation: Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, BP217X, 38043 Grenoble, France; Laboratory of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, 38043 Grenoble, France; HP2 laboratory INSERM U1042, Joseph Fourier University, Grenoble, France.
authors.forename: R
authors.initials: R
authors.lastname: Boizel
authors.affiliation: Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, BP217X, 38043 Grenoble, France; Laboratory of Biochemistry, Toxicology and Pharmacology, Grenoble University Hospital, 38043 Grenoble, France; HP2 laboratory INSERM U1042, Joseph Fourier University, Grenoble, France.
authors.forename: S
authors.initials: S
authors.lastname: Halimi
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D006266:Health Education; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011446:Prospective Studies; D013929:Thromboxane B2 / Q000652:urine
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013929:Thromboxane B2; D017999:Leukotriene E4
keywords: Blood glucose variability; Flexible insulin therapy; Leukotriene E4–11-dehydro-thromboxane B2; Therapeutic education; Type 1 diabetes