Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Combination chemotherapy with cytosine arabinoside, cyclophosphamide and L-asparaginase (Asnase) was given to 22 children with acute lymphocytic leukaemia (ALL) with a white-cell count greater than 30 X 10(9)/1, and other features suggestive of poor prognosis. Complete remission was induced in all patients--in 19 after 2 courses of chemotherapy and in the remainder after a third course. During induction, neutropenia occurred in 18 and severe infection in 3. Anaphylaxis to Asnase occurred in 8 patients after the second course and one other had transient Asnase-induced diabetes. All patients received central-nervous-system prophylaxis after achieving remission, during which they were also treated with weekly vincristine and a 2-week course of prednisolone. Continuation therapy consisted of short cycles of intermittent chemotherapy and BCG inoculation or long cycles of intermittent chemotherapy +/- BCG. Life-table analysis shows 46% complete remission rate at 28 months, with 6 patients all in complete remission followed up between 28 and 41 months. There were minimal complications of continuation therapy, and BCG inoculation was well tolerated.
 ...
PMID:Treatment of childhood lymphocytic leukaemia with high white-cell counts. 72 50

A case of a 11-year girl with the acute lymphoblastic leukemia is presented. Patient was treated with L-asparaginase and developed a transient but lasting several weeks diabetes mellitus with ketoacidosis as a sequelae of this therapy.
 ...
PMID:[Transient diabetes mellitus with ketoacidosis in a child during the treatment of acute lymphoblastic leukemia with L-asparaginase]. 140 32

A 51-year-old black woman with diabetes mellitus developed severe hepatotoxicity after receiving high-dose L-asparaginase (Elspar) for acute lymphatic leukemia. Patients with diabetes should be given this drug cautiously. Glutaminase-free L-asparaginase from Vibrio succinogenes has been reported to be less hepatotoxic in mice; it might be a safer product for this group of patients.
 ...
PMID:Severe hepatotoxicity from Escherichia coli L-asparaginase. 330 69

Ten children with acute lymphocytic leukemia developed transient diabetes mellitus during treatment with L-asparaginase and prednisone. Serum glucose, plasma insulin, and plasma glucagon levels were measured when the patients were hyperglycemic. Six of the children were restudied several months later when there were no clinical or laboratory signs of glucose intolerance. Hyperglycemia induced by L-asparaginase and prednisone was associated with depression of plasma insulin and, despite the inhibiting action of L-asparaginase on protein synthesis, a corresponding elevation of plasma glucagon. Thus patients with diabetes mellitus induced by L-asparaginase and prednisone have relative hyperglucagonemia similar to other patients with diabetes mellitus.
 ...
PMID:Relative hyperglucagonemia in L-asparaginase-and prednisone-induced glucose intolerance in management of acute lymphocytic leukemia. 634 Sep 6

Oral glucose tolerance tests were performed in 47 children with acute lymphoblastic leukemia (ALL), treated according to 2 consecutive protocols. Glucose and insulin values were assessed before and after L-asparaginase (L-asp). 30 children (group A) received L-asp as a single-agent consolidation course, after achieving remission with vincristine (VCR) and prednisone (PDN). Normal insulin and glucose levels were found in all patients before L-asp; 4 children (13%) had a transient impaired glucose tolerance (IGT) after completing L-asp therapy. 17 children (group B) were given L-asp during induction therapy with VCR and PDN, and all achieved complete remission. 5 patients (23%) had IGT, without hypoinsulinemia, before L-asp administration. IGT normalized in 4 patients after L-asp, the other children developed a diabetes mellitus. Only 1 patient, with a normal IGT test before L-asp therapy, showed a transient IGT after L-asp. In patients with ALL, the presence of IGT before treatment may be related to leukemia. The concomitant use of steroids does not influence the incidence of IGT in our series. Our data reveal normal insulinemia in patients with IGT. Thus, the leukemic process itself may play a much more significant role in inducing abnormalities in carbohydrate metabolism.
 ...
PMID:Glucose metabolism in children with acute lymphoblastic leukemia treated according to two different L-asparaginase schedules. 644 22

We determined retrospectively the frequency and risk of hyperglycemia in 421 children with leukemia who had received L-asparaginase and prednisone as part of their remission induction therapy. Forty-one patients (9.7%) developed this complication, 39 within one week after the first dose of L-asparaginase. Hyperglycemia resolved in all patients and in 32 before the end of the four-week induction period. Age, obesity, and Down syndrome each had a significant bearing on the frequency of hyperglycemia. Children 10 years of age or older were more likely to develop the complication than were younger children. When more than one factor was present in a child, the risk of hyperglycemia increased significantly. A family history of diabetes mellitus also appeared related to an increased risk of hyperglycemia. Childhood leukemia patients with any of the risk factors identified here should be closely monitored for glucosuria while receiving prednisone and L-asparaginase for remission induction.
 ...
PMID:Risk factors for hyperglycemia in children with leukemia receiving L-asparaginase and prednisone. 645 71

Twenty-seven male New Zealand White rabbits were injected with a single dose of 10,000 IU E. coli L-asparaginase per kilogram body wt to document the diabetogenic activity of this antitumor agent. Significant weight loss was observed by day 1, and a loss continued until day 9. After day 16, weight steadily increased. Random serum glucose levels increased steadily after the injection of L-asparaginase, reaching a peak value of 344 +/- 32 mg/dl (x- +/- SEM) on day 10. From day 12, levels declined, but they remained significantly higher than basal levels. Serum immunoreactive insulin (IRI) levels had a similar pattern of response. By day 2 the IRI was significantly above baseline. The IRI levels increased daily, reaching a peak level of 1,379 +/- 587 pg/ml (x- +/- SEM). Thereafter the levels fell gradually. However, the IRI levels remained significantly higher than basal levels. Intravenous regular insulin decreased glucose levels in L-asparaginase-treated animals at 3 h by only 7.7 +/- 3.2%, while it decreased them in controls by 34.0 +/- 6.7% (P less than 0.0025). These data demonstrate that, acutely, a single intravenous dose of 10,000 IU E. coli L-asparaginase per kilogram body wt induces a hyperinsulinemic. Insulin-resistant, diabetic syndrome in rabbits.
Diabetes 1980 Jul
PMID:L-Asparaginase-induced diabetes mellitus in rabbits. 699 39

Male New Zealand White Rabbits were injected intravenously with either a single dose of 10,000 IU Escherichia coli L-asparaginase/kg body weight containing 80 mg of D-mannitol/10,000 IU E. coli L-asparaginase or 80 mg D-mannitol kg/body weight alone. Elevated fasting glucose (G) and elevated fasting immunoreactive insulin (IRI) levels were observed in the L-asparaginase treated rabbits at 1 wk. They peaked at 3 wk and declined thereafter. However, fasting G and IRI levels remained significantly elevated at the end of the study (9-15 wk after injection) compared to preinjection levels and levels of the controls. Glucose and IRI levels 0.5 hr post and intravenous glucose load (1 g/kg body weight) also became elevated post L-asparaginase and followed a time course similar to that of the fasting G and IRI levels. These 0.5-hr levels also remained significantly elevated at the end of the study. These data show that a single dose of 10,000 IU/kg body weight produced a hyperinsulinemic diabetes in New Zealand White Rabbits that appears to persist in a mild form for at least 9-15 week.
 ...
PMID:Glucose tolerance an insulin release in L-asparaginase treated rabbits. 700 18

Hyperglycemia may occur as a complication in patients with leukemia during induction therapy with L-asparaginase and steroids. The reported incidence is about 10%. The present report concerns three patients with acute lymphoblastic leukemia (ALL), complicated by hyperglycemia. Their ages were 10, 12, and 9 years, respectively. Past histories were normal, with no diabetes mellitus or other endocrine disorders in their families. Case 1 was an obese boy who developed pancreatitis and diabetic ketoacidosis (DKA) in his remission induction therapy which had included both L-asparaginase and steroids. Cases 2 and 3 both presented with polyuria and elevated postprandial blood sugar. For all patients, insulin was administered to control their blood sugars; the maximal daily dosage of insulin dispensed was 2.1 U/kg, 0.5 U/kg, and 0.7 U/kg, respectively. Increased plasma insulin and C-peptide levels suggestive of insulin resistance were observed in Case 3. The outcome of hyperglycemia in these three patients was good. The symptoms of this complication may vary from mild glucose intolerance to severe, or even fatal, DKA. Thus, periodic determinations of urine glucose and postprandial blood sugar are important for early recognition to prevent further life-threatening consequences.
 ...
PMID:Hyperglycemia induced by chemotherapeutic agents used in acute lymphoblastic leukemia: report of three cases. 828 94

A randomized clinical trial of combination chemotherapy for adult acute lymphoblastic leukemia (ALL) with doxorubicin, vincristine and prednisolone with and without L-asparaginase (AdVP vs L-AdVP) was conducted, involving 58 institutions throughout Japan. After reaching complete remission (CR), patients were treated with the same regimen for more than 2 years. Among 166 evaluable cases of the 198 cases enrolled, CR rates were 63.1% (53/84) with AdVP and 64.6% (53/82) with L-AdVP (P = 0.837). Median survival times and 7-year survival rates were 12.7 months and 21.2% with AdVP, and 16.0 months and 22.3% with L-AdVP (P = 0.955 by generalized Wilcoxon test [GW], P = 0.952 by log-rank test [LR]). Median disease-free survival times and 7-year survival rates were 13.5 months and 23.8% with AdVP and 17.0 months and 30.6% with L-AdVP, showing some increments for L-AdVP but no statistical significance (P = 0.141 by GW, P = 0.300 by LR). Among the cases of extramurally confirmed FAB subtypes, CR rates were 75.9% (63/83) for the L1 subtype and 51.3% (39/76) for the L2 subtype (P = 0.001). As to adverse effects, pancreatitis was complicated more frequently in L-AdVP than in AdVP (P = 0.039). Other side effects such as hyperbilirubinemia, diabetes mellitus, diarrhea and hypofibrinogenemia were observed more frequently with L-AdVP, but with no statistical significance. Thus, addition of a single course of L-asparaginase in the induction phase of combination chemotherapy with doxorubicin, vincristine and prednisolone did not significantly enhance the effect of antileukemic treatment of adult ALL.
 ...
PMID:Nation-wide randomized comparative study of doxorubicin, vincristine and prednisolone combination therapy with and without L-asparaginase for adult acute lymphoblastic leukemia. 830 8


1 2 3 Next >>