Effect of the Tyrosine Kinase Inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) On Blood Glucose Levels in Diabetic and Non-Diabetic Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4265-4265
Author(s):  
Nicole M. Agostino ◽  
Vernon M Chinchilli ◽  
Anita Koszyk-Szewczyk ◽  
Rebecca Gingrich ◽  
Jeff Sivik ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels

Abstract Abstract 4265 Background Tyrosine kinase is a key enzyme utilized in many intracellular messaging pathways. Understanding of the role of particular tyrosine kinases in various malignancies has allowed for the design of compounds, the tyrosine kinase inhibitors (TKIs), which can specifically target these enzymes and hence, interfere with downstream signaling. TKIs have proven to be very successful in the treatment of a wide variety of malignant diseases including chronic myeloid leukemia, Philadelphia chromosome positive acute lymphoblastic leukemia, renal cell carcinoma and gastrointenstinal stromal tumors. Given the widespread nature of tyrosine kinase as a target and the promiscuous nature of the various inhibitors, it would not be surprising that these drugs would have effects beyond the expected result of targeting merely the tyrosine kinase of interest. Scattered reports have suggested that these agents appear to affect blood glucose levels. Results We studied the blood glucose levels retrospectively in diabetic (19) and non-diabetic (82) patients treated with dasatinib (8), imatinib (39), sorafenib (23) and sunitinib (30). All 4 drugs resulted in statistically significant decreased blood glucose levels in both diabetic and non-diabetic patients that resolved with cessation of treatment. Mean decreases blood glucose values for both non-diabetic and diabetic patients for dasatinib were – 53 mg/dl, imatinib – 9 mg/dl, sorafenib – 12 mg/dl and sunitinib -14 mg/dl. While diabetic and non-diabetic patients had the same decreases in blood glucose, on average, blood glucose values overall were 40 mg/dl lower in non-diabetic patients than in diabetic patients on dasatanib and imatinib. Non-diabetics had an overall mean blood glucose value of 24 mg/dl lower than diabetic patients on sorafenib, and 15 mg/dl lower than diabetic patients on sunitinib. Diabetic patients required some modifications of their medications including cessation of insulin or other hypoglycemic agents. One diabetic patient developed symptomatic hypoglycemia on sunitinib. Discussion The mechanism for the hypoglycemic effect of these drugs is unclear, but of the 4 agents tested, c-kit is a common target. C-kit has been shown to play a role in pancreatic β-cell survival in mouse models, so it is unclear why an inhibitor of the c-kit tyrosine kinase would improve blood glucose levels. It is important for clinicians to keep the potentially hypoglycemic effects of these agents in mind in their patients since symptomatic hypoglycemia can occur and modification of hypoglycemic agents may be required. These results also suggest that inhibition of a tyrosine kinase, be it c-kit or some other undefined target, may improve diabetes mellitus and deserves further study as a potentially therapeutic option. Disclosures: No relevant conflicts of interest to declare.

Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice

2010 ◽  
Vol 17 (3) ◽  
pp. 197-202 ◽  
Author(s):  
Nicole M Agostino ◽  
Vernon M Chinchilli ◽  
Christopher J Lynch ◽  
Anita Koszyk-Szewczyk ◽  
Rebecca Gingrich ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Blood Glucose ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Glucose Levels ◽  
Blood Glucose Levels

Erythropoietin Treatment Is Associated with Decreased Blood Glucose Levels: A Preliminary Study in Hematologic Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4793-4793
Author(s):  
Howard S Oster ◽  
Moran Gvili ◽  
Odelia Katz ◽  
Michael Hoffman ◽  
Drorit Neumann ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Repeated Measures ◽  
Mixed Model ◽  
Conflicts Of Interest ◽  
Cell Lineage ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Organ Systems ◽  
Average Glucose

Abstract Abstract 4793 Introduction: Erythropoietin (EPO) is the major hormone which enhances proliferation and maturation of the red cell lineage, and its recombinant form (rHuEPO) is used extensively to treat various types of anemia. rHuEPO has also been found to exert effects in other organ systems, and our previous work has demonstrated an immunomodulatory role for EPO. Recently, we have also found that mice exposed to high levels of EPO (either rHuEPO injections or transgenic mice overexpressing human EPO), have significantly lower levels of blood glucose than those of their respective controls (Katz et al., J Endocrinol 2010;205:87-95). The current retrospective study was designed to determine whether rHuEPO treatment in hematologic patients, is associated with decreased blood glucose levels. Methods: Patients receiving rHuEPO were examined, comparing glucose levels (morning blood tests, assumed to be fasting) while on rHuEPO treatment to those off treatment. All patients served as their own controls. To test the association between rHuEPO treatment and blood glucose levels, we employed a mixed-model repeated-measures analysis of variance (ANOVA). Results: The charts of 19 patients were reviewed to determine the starting date of rHuEPO and the levels of blood glucose in relation to rHuEPO treatment. Mean age: 77 (range: 54–93). Thirteen patients had myelodysplastic syndrome, and six had multiple myeloma. Two patients had diabetes mellitus. Average glucose levels (mean±95%CI) without rHuEPO treatment were 116.07±4.98. Glucose measurements were available for a median of 9.23 (interquartile range: 7.90–16.80) months after the initiation of rHuEPO treatment. The average glucose level over that period of time was 101.77±4.86 (p<0.0001). The two diabetic patients also demonstrated a trend towards reduced serum blood glucose and lower HbA1C while being treated with rHuEPO. Conclusions: Treatment of hematologic patients with rHuEPO is associated with significantly lower blood glucose levels, and might serve in the future to improve glucose control in anemic patients with hyperglycemia. Further studies with both diabetic and non-diabetic patients are currently underway to clarify this association. Disclosures: No relevant conflicts of interest to declare.

MicroRNAs Mediate Resistance to Tyrosine Kinase Inhibitors in Philadelphia-Positive B-ALL by Down-Regulating Key Tumor Suppressors

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2553-2553
Author(s):  
Jonathan H. Schatz ◽  
Konstantinos Mavrakis ◽  
Andrew L Wolfe ◽  
Hans-Guido Wendel
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Conflicts Of Interest ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Clinical Problem ◽  
Oncogenic Signaling ◽  
Down Regulation ◽  
Tki Resistance

Abstract Abstract 2553 The Philadelphia (Ph) chromosome (t(9;22)(q34;q11)) is the most common recurrent cytogenetic abnormality in adult B-cell acute lymphoblastic leukemia (B-ALL). Resulting expression of the BCR-ABL fusion gene product, a constitutively active tyrosine kinase, leads to an extremely poor prognosis when the disease is treated with chemotherapy alone. In recent years targeted therapy with tyrosine kinase inhibitors (TKIs) in combination with chemotherapy has improved outcomes. Therapeutic resistance remains a major clinical problem, however, with less than half of patients surviving three years from initial therapy in most series even with up-front TKI-chemotherapy regimens. TKI resistance in B-ALL may result from acquired mutations of the BRC-ABL protein or from BCR-ABL-independent causes, including feedback activation of BCL6 or activation of other oncogenic signaling pathways through poorly understood mechanisms. In this study, we screened a whole-genome library of microRNAs for ability to produce resistance to TKI therapy in murine pro-B cells transformed with BCR-ABL. Several initial candidates from the screen were individually confirmed to confer TKI resistance, including miR 148/152 and 19, known oncomirs in T-ALL. Computational analysis of the gene targets of validated miRs shows significant overlap at several tumor-suppressor pathways, including down-regulation of PTEN, a known mechanism of TKI resistance in Ph+ B-ALL cell lines. In sum, we have identified a novel mechanism of TKI resistance in Ph+ B-ALL mediated by miRs and leading to down-regulation of specific tumor suppressive intermediates. These findings will allow development of new therapeutic combinations to improve outcomes for B-ALL patients. Disclosures: No relevant conflicts of interest to declare.

Comparative Analysis of Tyrosine Kinase Inhibitors-Related Pulmonary Hypertension in the Patients Treated By Imatinib, Dasatinib and Nilotinib

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1583-1583
Author(s):  
Mariko Minami ◽  
Toshihiro Miyamoto ◽  
Takeshi Arita ◽  
Tomohiko Kamimura ◽  
Junichiro Yuda ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Dependent Manner ◽  
Pulmonary Hemodynamics ◽  
Significant Difference ◽  
Dasatinib Treatment

Abstract Introduction: Tyrosine kinase inhibitors (TKIs) have dramatically improved outcome of patients with chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) with lesser incidence of serious adverse events. Recently, cases with fatal pulmonary hypertension (PH) have been sporadically documented in association with dasatinib treatment. French group reported incidence of PH diagnosed by cardiac catheterization as 0.45% (13 of 2900 patients) in the symptomatic patients treated with dasatinib. In contrast, a Korean group prospectively evaluated PH by non-invasive echocardiography in CML patients treated with dasatinib, and demonstrated 8 of 66 patients (12.1%) exhibited a significant increase in right ventricular systolic pressure, indicating subclinical PH might be more common event in dasatinib-treated patients. In this study, we prospectively examined the patients treated with three TKIs by echocardiography to clarify incidence of clinical and subclinical PH as well as factors associated with PH. Patients and Methods: Total of 108 patients (99 with CML, 9 with Ph+ ALL) receiving TKIs in our institutions were enrolled to this study. Forty-one patients have been on treatment with dasatinib (38%), 37 with imatinib (34%) and 30 with nilotinib (28%). Patients underwent echocardiography to evaluate values of tricuspid regurgitation pressure gradient (TRPG), which relates to severity of PH. Patients with higher values of TRPG than the upper limit (30mmHg) was suspected of PH by European Society of Cardiology criteria. Results: Among 108 patients, median age was 63 years old, and median duration of TKIs treatment was 26.5 months. Median daily dosage was 100 mg for dasatinib, 300 mg for imatinib, 600 mg for nilotinib groups, respectively (Table 1). In imatinib group, patients' age was significantly higher, and duration of treatment was also longer than those of the 2nd generation TKIs. Echocardiography revealed mean values of TRPG as 23.2, 23.2 and 23.1 mmHg in dasatinib, imatinib and nilotinib groups, respectively. There was no significant difference in TRPG values among 3 groups (p=0.99). We also found no relationship between TRPG values and duration of TKIs treatment in each group. Interestingly, we detected a significant inverse correlation between daily dosage of imatinib and TRPG values (p=0.012, Figure 1), while such relationship was not observed in dasatinib and nilotinib groups (p=0.68 and p=0.49). TRPG values higher than 30 mmHg were documented in 13 of 108 patients (12.0%); 5 of 41 (12.2%) in dasatinib group, 4 of 37 (10.8%) in imatinib group, and 4 of 30 (13.3%) in nilotinib group (p=0.95). Discussion: PH is characterized by proliferation of pulmonary vascular smooth muscle cells (SMCs). Recent reports showed that imatinib suppresses abnormal proliferation of SMCs through inhibiting platelet-derived growth factor receptors (PDGFR), resulting in improvement of PH in animal models. Clinical studies in symptomatic PH patients reported that imatinib considerably improved pulmonary hemodynamics. Of note, in our study, dosage of imatinib was significantly correlated with lower values of TRPG, suggesting imatinib possibly decreases TRPG values in a dose-dependent manner. This finding strongly supports the reports indicating imatinib as a therapeutic agent of PH. In contrast, in vitro studies have shown that dasatinib has stronger potential to inhibit PDGFR compared to imatinib; nevertheless, onsets of PH have been reported in dasanitib-treated patients, but not with imatinib nor nilotinib. Our study demonstrated the incidence of TRPG elevation as 12.0% in dasatinib group, which was consistent with Korean report (12.1%). However, there was no significant difference in TRPG values among 3 groups, indicating no apparent evidence which dasatinib treatment might be specifically associated with occurrence of PH. These results suggested that subclinical PH might be more common than expected. Careful follow-ups with echocardiography are necessary for the patients under any TKI treatments. Table 1. Patient characteristics Dasatinib group (n=41) Imatinib group (n=37) Nilotinib group (n=30) p Median age 55(17-77) 68(22-92) 62.5(24-85) 0.0004 Median dosage (mg/day) 100(18-100) 300(100-600) 600(300-800) Mean months from start of TKI 68.5(2-287) 104.8(2-228) 61.3(3-153) 0.007 Mean TRPG(mmHg) 23.2(9-40) 23.2(8-46) 23.1(7-35) 0.995 Disclosures No relevant conflicts of interest to declare.

Effects of exercise on blood glucose levels in type 2 diabetic patients – Literature review

2018 ◽  
Author(s):  
Apolinary Ginszt ◽  
◽  
Michał Ginszt ◽  
Piotr Majcher ◽  
Zbigniew Tarkowski ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Literature Review ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Type 2 Diabetic

Nutritional Interventions and Considerations for the Development of Low Calorie or Sugar Free Foods

2020 ◽  
Vol 16 (4) ◽  
pp. 301-312 ◽  
Author(s):  
Jyoti Singh ◽  
Prasad Rasane ◽  
Sawinder Kaur ◽  
Vikas Kumar ◽  
Kajal Dhawan ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Blood Glucose ◽  
Human Population ◽  
Artificial Sweeteners ◽  
Diabetic Patients ◽  
Nutritional Interventions ◽  
Low Calorie ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Diet Plan

Diabetes is a globally prevalent chronic metabolic disease characterized by blood glucose levels higher than the normal levels. Sugar, a common constituent of diet, is also a major factor often responsible for elevating the glucose level in diabetic patients. However, diabetic patients are more prone to eat sweets amongst the human population. Therefore, we find a popular consumption of zero or low-calorie sweeteners, both natural and artificial. But, the uses of these sweeteners have proved to be controversial. Thus, the purpose of this review was to critically analyze and highlight the considerations needed for the development of sugar-free or low-calorie products for diabetic patients. For this purpose, various measures are taken such as avoiding sugary foods, using natural nectar, artificial sweeteners, etc. It cannot be ignored that many health hazards are associated with the overconsumption of artificial sweeteners only. These sweeteners are high-risk compounds and a properly balanced consideration needs to be given while making a diet plan for diabetic patients.

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