Diabetes mellitus and TKIS treatment in chronic myeloid leukemia

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterised by a pathognomonic chromosomal translocation t(9;22)(q34;q11.2) which results in the oncogenic BCR-ABL1 fusion gene, encoding for a mutant, continuously activated tyrosine kinase. Specific Tyrosin Kinase Inhibitors (TKIs) therapy, having this translocation as a target, dramatically improved life expectancy of CML patients. First (imatinib) and second generation TKIs (dasatinib and nilotinib) act on different molecular targets, leading to varying side effects; several studies have revealed that nilotinib induces hyperglycemia in a subset of non diabetic and diabetic CML patients, whereas imatinib and dasatinib usually do not. Aims: To evaluate the glico-metabolic assessment of CML patients treated with TKIs. Methods: A total of 90 unselected CML patients treated with TKIs and referred to our Hospital were included. Blood samples for fasting glycemia, insulin, c-peptide and other clinical variables as anthropometric parameters were collected for each patient. We studied Beta-cell function assessed by HOMA-IR and HOMA-beta with the aim to determine insulin-resistance and insulin-secretion, respectively. The diagnosis of diabetes was performed using criteria (updated 2010) from the American Diabetes Association (ADA). Results: In our population, DM was diagnosed in 12 patients (13.5%), whereas impaired fasting glucose (IFG) was reported in 22 patients (24.4%). Among the three TKIs, we have not found a significant difference in hyperglycemia and DM presence, although they were both higher in the nilotinib treated group. The same group showed higher basal insulin and c-peptide levels and higher HOMA-IR (p<0.05) than the others, without a significant difference in HOMA-beta. In all groups, diabetic patients showed higher HOMA-IR (p<0.05), BMI (p<0.01), weight (p<0.01), age (p<0.05) and triglycerids levels (p<0.01) than non DM, while HDL cholesterol levels were lower (p<0.05). Summary and Conclusions: Our data confirm the few reports in literature that show higher prevalence of IFG and DM in CML patients. The underlying mechanism is not clear but in our population, diabetic patients showed higher insulin-resistance and BMI, whereas insulin secretion was not reduced.