title: Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients: a real clinical problem?
abstract: BACKGROUND
  Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML-chronic phase patients treated with imatinib, dasatinib or nilotinib.
  
  
  METHODS
  The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS. Anthropometric and metabolic parameters were assessed, and DM/IFG and MS were diagnosed based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively.
  
  
  RESULTS
  The nilotinib group had significantly higher levels of fasting plasma glucose, insulin, C-peptide, insulin resistance, and total and LDL cholesterol than the imatinib and dasatinib groups. DM/IFG were identified in 25% of the imatinib- and dasatinib-treated patients, and 33% of those in the nilotinib cohort (p = 0.39 vs imatinib and p = 0.69 vs dasatinib). A diagnosis of MS was made in 42.4% of the imatinib-treated patients, 37.5% of the dasatinib-treated patients, and 36.1% of the nilotinib-treated patients (p = 0.46 vs imatinib and p = 0.34 vs dasatinib).
  
  
  CONCLUSIONS
  Treatment with nilotinib does not seem to induce DM/IFG or the MS to a significantly higher extent than imatinib or dasatinib, though it causes a worse glycometabolic profile. These findings suggest the need for a close monitoring of glucose and lipid metabolism and a multidisciplinary approach in patients treated with nilotinib.
authors.affiliation: Oncohematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy.|Oncohematology Unit of The Elderly, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Iurlo
authors.affiliation: Endocrinology and Diabetes Unit, Department of Medical Sciences, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Orsi
authors.affiliation: Oncohematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Cattaneo
authors.affiliation: Endocrinology and Diabetes Unit, Department of Medical Sciences, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Resi
authors.affiliation: Oncohematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bucelli
authors.affiliation: Oncohematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Orofino
authors.affiliation: Oncohematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy.
authors.forename: Mariarita
authors.initials: M
authors.lastname: Sciumè
authors.affiliation: Oncology-Hematology Department, Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Elena
authors.affiliation: Endocrinology and Diabetes Unit, Department of Medical Sciences, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Grancini
authors.affiliation: Epidemiology Unit, Department of Preventive Medicine, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Consonni
authors.affiliation: Oncology-Hematology Department, Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Ester Maria
authors.initials: EM
authors.lastname: Orlandi
authors.affiliation: Oncohematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000886:Anthropometry; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D015331:Cohort Studies; D000069439:Dasatinib / Q000627:therapeutic use; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D005947:Glucose; D000069439:Dasatinib
keywords: dasatinib; diabetes mellitus; imatinib; metabolic syndrome; nilotinib