Lipoatrophy in children, adolescents and adults with insulin pump treatment: Is there a beneficial effect of insulin glulisine?

AIM: To investigate whether zinc-free insulin is an effective treatment option for lipoatrophy. METHODS: Controlled, randomized, open-label parallel study in young people with type 1 diabetes, pump treatment and lipoatrophy at injection sites. Participants underwent dermatological examination and evaluation of affected areas using ultrasound and magnetic resonance imaging (MRI). After randomization, half of themswitched to insulin glulisine (intervention group) for 6 months. The control group continued their treatment with zinc-containing insulin and switched to insulin glulisine 6 months later. Both groups were followed-up until month 12. Primary endpoint was the increase of the relative thickness of the subcutaneous fat layer of the most atrophic site at 6 months as documented by MRI. RESULTS: Fourteen participants were included into the study. While relative thickness of subcutaneous fat tissue was comparable between intervention (-60% [-98.8 - -17.6], n = 7) and control group (-50% [-72.7 - -1.0], P = .511; median (range), n = 7)at baseline, it improved in the intervention (-14.3% [-85.7-83.3] vs -31.3% (-66.7-0), P = .031), but not in the control group (P = .125) after 6 months. At 12 months, relative fat thickness (P = .003), number (P = .015) and size of most atrophic sites (P = .001) were improved in the intervention group. Number (P = .018) and size of most atrophic sites (P = .008) were also reduced in the control group between 6 and 12 months. CONCLUSIONS: Although the present pilot study is based on a small sample, the data give first hint that the use of the zinc-free insulin glulisine may be beneficial in people with diabetes, pump and lipoatrophy.

Sensor augmented pump therapy from onset of type 1 diabetes: late follow-up results of the Pediatric Onset Study.

AIM: To evaluate the metabolic control and ß-cell function 1 yr after the end of the European multicentre randomized Pediatric Onset Study. METHODS: Of 154 study patients, 131 were re-examined 24 months after type 1 diabetes onset (49.6% boys, age at onset 8.9 ± 4.3 yrs). Of which, 62 patients belonged to the primary group of the main study applying a sensor-augmented pump system during the first yr and 69 patients to the control group performing conventional insulin pump therapy with self-monitoring blood glucose. HbA1c, fasting blood glucose, and C-peptide were centrally measured (Clinical Trail Registration Number: ISRCTN05450731). RESULTS: At 24 months, i.e., 1 yr after the end of the interventional study, 52.4% of the patients used the sensor-augmented pump system, 46.0% conventional pump, and 1.6% multiple daily injections. HbA1c was 7.6 ± 1.3% in the primary and 7.7 ± 1.2% in the control group (p = 0.493). Frequent sensor use during the first yr was associated with statistically insignificant lowering of the HbA1c at 24 months (p = 0.236) as compared with irregular or no sensor use (7.4 ± 1.0% vs. 7.7 ± 1.3%). Although fasting C-peptide was not clearly different between the primary and control group (0.13 ± 0.17 vs. 0.09 ± 0.10 nmol/L, p = 0.121), patients with frequent sensor use had significantly less C-peptide loss within 24 months (C-peptide reduction 0.02 ± 0.18 vs. 0.07 ± 0.11 nmol/L, p = 0.046). There was no difference between the groups regarding daily insulin requirements. CONCLUSION: Sensor-augmented pump therapy from onset of diabetes may lead to better long-term glycemic control and help to preserve endogenous ß-cell function, if patients comply with frequent use of continuous glucose monitoring.

Benefit of supplementary fat plus protein counting as compared with conventional carbohydrate counting for insulin bolus calculation in children with pump therapy.

OBJECTIVE: To investigate carbohydrate (CARB) and supplementary fat/protein (CFP) counting using normal and dual-wave bolus in pump therapy of children and young people with type 1 diabetes (T1D). STUDY DESIGN AND METHODS: A randomized clinical trial was conducted in 42 patients (age 6-21 yr) with T1D for at least 1 yr (5.2 ± 3.1 yr, mean ± SD) and pump therapy for at least 3 months (3.3 ± 1.8 yr). Standardized test meals (pizza-salami; 50% carbohydrate, 34% fat, 16% protein; corresponding to 33% of age-adjusted daily energy requirement) were given at lunch time on four different days with normal and dual-wave bolus using CARB and CFP counting in a randomized sequence. Sensor-augmented pumps were used for continuous glucose monitoring of 6-h postprandial glucose profiles. Intra-individual comparisons of glucose parameters [area under the curve (AUC) mg/dL × 6 h; average glucose, AV mg/dL] were performed. RESULTS: Using CFP counting, 6-h postprandial glucose AUC (805 ± 261) and AV (137.8 ± 46.2) were significantly lower than AUC (926 ± 285) and AV (160.5 ± 51.9) by CARB counting (p < 0.001, each). CFP counting led to significantly lower postprandial glucose parameters independently from the kind of bolus (normal bolus: ΔAUC 169, p < 0.001; ΔAV 30.6, p < 0.001/dual-wave bolus: ΔAUC 73, p = 0.045, ΔAV 14.8, p = 0.033). Postprandial hypoglycemia episodes (<70 mg/dL) occurred more frequently in CFP than in CARB counting (35.7% vs. 9.5%, p < 0.001). No severe hypoglycemia was reported. CONCLUSION: In patients with long-term T1D, meal-related insulin dosing based on carbohydrate plus fat/protein counting reduces the postprandial glucose levels (ClinicalTrials.gov NCT01400659).

GADA positivity at onset of type 1 diabetes is a risk factor for the development of autoimmune thyroiditis.

AIM: To evaluate whether the presence of diabetes-specific autoantibodies may predict the development of autoimmune thyroiditis (AIT) in children with type 1 diabetes (T1D). METHODS: Glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase IA2 antibodies (IA2A), and insulin autoantibodies (IAA) were determined at T1D onset in 341 children and adolescents. Thyroid antibodies (anti-TG, anti-TPO), thyroid stimulating hormone (TSH), T(3) and T(4) were measured in 335 patients at T1D onset and thereafter annually with a follow-up time of 1-15 yr. In case of thyroid antibody positivity and/or TSH elevation, thyroid gland sonography was performed. Treatment with l-thyroxine was started if persistent elevation of TSH and/or thyroid volume was present. RESULTS: The majority of patients (92.1%) had at least one T1D antibody (71.6% GADA, 73.0% IA2A, and 44.9% IAA). GADA positive patients were older than those without GADA (p < 0.001). Thyroid autoimmunity was found in 15 of 335 patients (4.5%) at T1D onset with female preponderance (p = 0.013). At the end of follow-up, 70 patients (20.9%) had developed thyroid autoantibodies [cumulative incidence (CI) 0.36 ± 0.06 at 10 yr of T1D]. In 30 patients (9.0%), AIT was diagnosed up to 9.4 yr after T1D onset (CI 0.24 ± 0.06 at 10 yr). AIT incidence was not influenced by IAA or IA2A positivity. In multivariate analysis, GADA positive patients were estimated to have a 3.5-fold increased risk of AIT (CI 0.31 ± 0.11 at 10 yr) compared to those without GADA (p = 0.024). CONCLUSION: Based on the present results, a special focus should be given to GADA positive patients concerning screening for AIT as they are at increased risk to develop autoimmune thyroiditis.

Secondary malignant neoplasms after intensive treatment of relapsed acute lymphoblastic leukaemia in childhood.

PURPOSE: To investigate the cumulative incidence of and the risk factors for developing second malignant neoplasms (SMN) in children and adolescents following treatment for relapse of acute lymphocytic leukaemia (ALL). METHODS: Patients (1376) up to 18 years of age with first relapse of non-B-cell ALL were treated and achieved a 2nd complete remission (CR). The treatment followed trial protocol in five consecutive multicentre trials of the ALL-REZ BFM Study Group between March 1983 and December 2001. The incidence of SMN was analysed, correlated with clinical and therapeutic parameters, and compared to the age-specific incidence rates of cancers as cited in German cancer registries. RESULTS: Out of the 1376 patients 21 were diagnosed with SMN including non-lymphoblastic leukaemia/myelodysplastic syndrome (n=6), osteo-/Ewing's-/fibroblastic sarcoma (n=4), B-cell ALL/lymphoma (n=2), thyroid carcinoma (n=2), basal cell carcinoma, adeno carcinoma, squamous cell carcinoma, meningioma, malignant histiocytosis, glioblastoma and anaplastic astrocytoma (n=1 each). The overall cumulative risk of SMN at 15 years (median follow-up of 13.1 years) was 1.26%+/-0.38% (SE). SMN was found to be significantly associated with stem cell transplantation (SCT), and high cumulative doses of cranial irradiation, etoposide and cyclophosphamide. In multivariate analysis etoposide (VP16) and cyclophophamide (CY) were found to be independently associated with SMN (p=0.047 and 0.002). Compared to the incidence of neoplasm in the age-matched population, there was a 10-fold increase of neoplasia. CONCLUSIONS: Despite repeated exposure to intense frontline and relapse treatment (including multiagent chemotherapy, cranial irradiation and stem cell transplantation in some patients) the cumulative incidence of SMN was unexpectedly low, though significantly higher than in the general age-matched population. The association of SMN to SCT seemed to be a secondary effect at least partially mediated by exposure to high doses of VP16 and CY given for conditioning therapy.

Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Münster Group 87.

PURPOSE: Approximately 20% of children with acute lymphoblastic leukemia (ALL) suffer a relapse, and their prognosis is unfavorable. Between 1987 and 1990, the multicenter trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 87 was conducted to establish a uniform treatment for these children in Germany and Austria. PATIENTS AND METHODS: Of 207 registered patients, 183 patients were stratified into three groups according to the protocol: A, early bone marrow (BM) relapse (n = 56); B, late BM relapse (n = 101); C, isolated extramedullary relapse (n = 26). Treatment consisted of risk-adapted alternating short-course multiagent systemic and intrathecal chemotherapy, cranial irradiation, if indicated, and conventional maintenance therapy. Additionally, 24 patients with an exceptionally poor prognosis (early BM or any relapse of T-cell ALL) were treated with individual regimens. In 35 patients, stem-cell transplantation was performed. RESULTS: The probability of event-free survival (EFS) and overall survival of all registered patients at 15 years was 0.30 +/- 0.03 and 0.37 +/- 0.03, respectively, with significant differences between the strategic groups (A, 0.18 +/- 0.05 and 0.20 +/- 0.05; B, 0.44 +/- 0.05 and 0.52 +/- 0.05; C, 0.35 +/- 0.09 and 0.42 +/- 0.10). Despite risk-adapted treatment, an early time point of relapse and T-lineage immunophenotype were significant predictors of inferior EFS in uni- and multivariate analyses. CONCLUSION: With the ALL-REZ BFM 87 protocol, more than one-third of patients may be regarded as cured from recurrent ALL with second complete remissions lasting more than 10 years. Immunophenotype and time point of relapse are important prognostic factors that allow us to adapt more precisely treatment intensity to individual prognosis in future trials.

Birth weight and parental BMI predict overweight in children from mothers with gestational diabetes.

OBJECTIVE: To investigate the growth of children from pregnancies with gestational diabetes mellitus (GDM) and its association with antenatal maternal, fetal, and recent anthropometric parameters of mother and father. RESEARCH DESIGN AND METHODS: In 324 pregnancies of Caucasian women with GDM, BMI before pregnancy, maternal glycemic values, and measurements of the fetal abdominal circumference were recorded. The weight and height of infants were measured at birth and at follow-up at 5.4 years (range 2.5-8.5). In addition, somatic data from routine examinations at 6, 12, and 24 months and the BMI of parents at follow-up were obtained. BMI standard deviation scores (SDSs) were calculated based on age-correspondent data. RESULTS: At all time points, BMI was significantly above average (+0.82 SDS at birth; +0.56 at 6, +0.35 at 12, and +0.32 at 24 months; and +0.66 at follow-up; P < 0.001). BMI at birth was related to BMI at follow-up (r = 0.27, P < 0.001). The rate of overweight at follow-up was 37% in children with birth BMI > or =90th percentile and 25% in those with normal BMI at birth (P < 0.05). Abdominal circumference of third trimester and postprandial glucose values were related to BMI at follow-up (r = 0.22 and r = 0.18, P < 0.01). Recent maternal, paternal, and birth BMI were independent predictors of BMI at follow-up (r = 0.42, P < 0.001). Sixty-nine percent of children of parents with BMI > or =30 kg/m(2) were overweight at follow-up compared with 20% of those with parental BMI <30 kg/m(2) (P < 0.001). CONCLUSIONS: Children of mothers with GDM have a high rate of overweight that is associated both with intrauterine growth and parental obesity.

Immunophenotypic cell lineage and in vitro cellular drug resistance in childhood relapsed acute lymphoblastic leukaemia.

At relapse, T-cell acute lymphoblastic leukaemia (ALL) has a worse patient outcome than B-cell precursor (BCP-) ALL. To investigate this further, we compared in vitro cellular drug resistance profiles of T-cell and BCP-ALL samples obtained at relapse. We investigated 237 paediatric relapsed ALL cases, including 151 samples taken at first relapse, of which 30 were T-cell ALL. In vitro drug resistance was measured using the 4-day methyl-thiazol-tetrazolium (MTT) assay and cellular immunophenotype was determined at central reference laboratories. Similar results were found for first relapsed ALL samples and for the total group: T-cell ALL samples were more resistant to 4-HOO-ifosfamide (1.4-fold, P = 0.019) and cisplatin (3.7-fold, P = 0.005). The samples were more sensitive to thiopurines such as mercaptopurine (2.1-fold, P = 0.007) and thioguanine (1.7-fold, P = 0.003). Resistance/sensitivity to 16 other drugs did not differ significantly. These results do not explain the relatively poor prognosis of T-cell ALL at relapse, but do suggest that the more intensive use of thiopurines in relapsed T-cell ALL may be beneficial.

Lipoatrophy in children with type 1 diabetes: an increasing incidence?

The objectives were to evaluate the current prevalence of lipoatrophy at insulin injection sites in young patients with type 1 diabetes. Standardized examination of insulin injection sites in all 678 patients with type 1 diabetes treated in 2013 in our outpatient clinic were conducted. In case of lipoatrophy photo documentation and standardized interview with parents and patients were performed. We identified a total of 16 patients (43.8% male) with lipoatrophy (overall prevalence 2.4%). The current mean age (±SD) of the affected patients was 14.4 ± 3.9 years, age and diabetes duration at onset of lipoatrophy were 11.5 ± 3.8 years and 5.4 ± 3.6 years, respectively. All patients were using analogs at the onset of lipoatrophy. In all, 14 of 16 patients (87.5%) were on insulin pump compared with 52% without lipoatrophy (P = .0018). The use of steel needle and Teflon catheter was equal between the pump patients. Concomitant autoimmune diseases were present in 37.5% of the patients (thyroiditis: n = 3, thyroiditis and celiac disease: n = 2, celiac disease: n = 1) compared with 15.0% in those without lipoatrophy (P = .0128). Lipoatrophy was present in young patients treated with modern insulins and pumps; however, the prevalence was relatively low as expected with the use of modern insulins. Our data may support the hypothesis that a constant mechanical element such as a subcutaneous catheter may trigger the development of lipoatrophy, particularly in those patients with more than 1 autoimmune disease.

Clonal stability of initial leukemia in a child with central nervous system relapse 7.4 years after bone marrow relapse of common acute lymphoblastic leukemic.

Second central nervous system (CNS) relapses represent about 7.3% of subsequent recurrences of childhood acute lymphoblastic leukemia (ALL). In most children these subsequent CNS relapses occur during the first 18 months after diagnosis of the first relapse (mean 1.42 +/- 0.73 years). We present a patient who suffered a second ALL relapse in the CNS more than seven years after diagnosis of his first relapse. The leukemic clone was completely stable over more than ten years as shown by minimal residual disease techniques. Possible reasons for the recurrence of the leukemic clone after this very long period of dormancy (e.g. role of the disease site, immune system dysfunction) are discussed.

Age-specific levels of diabetes-related GAD and IA-2 antibodies in healthy children and adults.

Glutamic acid decarboxylase (GAD) and tyrosine phosphatase IA-2 antibody levels were measured in 375 healthy children and adults and in 187 children with newly diagnosed type 1 diabetes mellitus (DM). GAD antibody levels were determined by radioimmunoassay, and IA-2 antibody levels by immunoprecipitation. Healthy children had higher GAD antibody levels than adults (p < 0.001). The 98th percentile was 1.60 U/ml in children and 1.16 U/ml in adults. IA-2 antibody levels did not differ between these two cohorts. Children with DM had higher GAD and IA-2 antibody levels than healthy children (p <0.001). Based on receiver operating characteristics (ROC) analysis, elevated levels of these antibodies showed high specificity rates (+/- SE) of 0.968 +/- 0.14 to 1.00 +/- 0.00. The sensitivity ranged between 0.439 +/- 0.037 (both antibodies elevated) and 0.850 +/- 0.027 (at least one antibody elevated). These data emphasize the importance of establishing age-specific reference values for DM-related antibodies in the background population before applying them for screening and intervention studies.

Prevalence of 20S proteasome, anti-nuclear and thyroid antibodies in young patients at onset of type 1 diabetes mellitus and the risk of autoimmune thyroiditis.

Patients with type 1 diabetes mellitus (DM1) are at high risk to develop further autoimmune disorders, which are mostly characterized by the presence of organ-specific antibodies in serum and a subclinical disease course. Diabetes-related (glutamic acid decarboxylase, tyrosine phosphatase, IA-2) and thyroid-specific (thyroperoxidase, thyroglobulin) as well as antibodies to 20S proteasome, and anti-nuclear antibodies, were measured at DM1 onset in 147 children and adolescents. Patients were followed prospectively for the development of autoimmune thyroiditis (TSH elevation and/or sonographic thyroid gland enlargement in the presence of thyroid antibodies) up to 12 years, median observation time 4.4 years. Eight of 147 (5.4%) patients developed autoimmune thyroiditis. The cumulative incidence (+/-SE) at 5 years was 0.08+/-0.03. The prevalence of thyroid antibodies was 16.7%, of DM-related 88.4%, 20S proteasome 21.9%, and anti-nuclear antibodies 20.0%. There was a positive correlation between thyroid and anti-nuclear antibodies (p <0.001). Clinical course of DM1 and remission duration were not influenced by the presence of autoantibodies. However, in contrast to patients without antibodies, those with positive antibodies had significantly (p <0.001) elevated cumulative incidence of autoimmune thyroiditis at 5 years: thyroperoxidase 0.40+/-0.13, thyroglobulin 0.38+/-0.15, and anti-nuclear antibodies 0.29+/-0.12, respectively. These data underline that autoimmunity in patients with DM1 is not only restricted to beta-cell antigens at the onset of disease. In particular, patients with positive thyroid and anti-nuclear antibodies are at high risk to develop autoimmune thyroiditis during the first 5 years of DM1.

Treatment of type 1 diabetes in children and adolescents using modern insulin pumps.

In the last decades, we are experiencing an increasing use of insulin pumps for the treatment of type 1 diabetes in children and adolescents. The most frequent reasons for switching from insulin injection schemes to pump therapy are frequent and/or severe hypoglycaemia, dawn phenomenon, poor glycaemic control, wish for more flexibility in daily life, and needle phobia. In toddlers and preschoolers, pumps are frequently introduced from the onset of type 1 diabetes. Pumps offer the possibility of adjusting basal insulin rates individually on an age-depended manner as well as of optimizing meal-related insulin requirements according to the meal composition by using three different kinds of boluses. Structured and intensive education of patients and their families on basics and specific requirements of insulin pump therapy is essential in order to get them familiar with the devices and their features. There is increasing evidence both from multicentre cross-sectional studies as well as from meta-analyses of randomized clinical trials in paediatric populations showing that patients with pump therapy can achieve a more favourable metabolic control accompanied with less hypoglycaemic events than those with multiple daily injections.

Prevention of hypoglycemia by using low glucose suspend function in sensor-augmented pump therapy.

BACKGROUND: Severe hypoglycemic episodes are a barrier for achieving optimal glycemic control. Sensor-augmented pump (SAP) therapy with insulin in combination with a novel mechanism of automatic insulin shutoff (low glucose suspend [LGS]) can be used to prevent and reduce hypoglycemia. In a prospective study, we investigated the effect of the LGS algorithm on the frequency of hypoglycemia in children and adolescents with type 1 diabetes under real-life conditions. METHODS: Twenty-one patients with type 1 diabetes (10.8±3.8 years old, duration of diabetes 5.9±3.0 years, pump therapy for 3.7±1.7 years, glycated hemoglobin level 7.8±1.1%) from three pediatric centers used the Paradigm(®) Veo(™) system (Medtronic Minimed, Northridge, CA) during two subseqent time periods: SAP without LGS for 2 weeks and then SAP with LGS enabled for 6 weeks. The primary objective was to assess the frequency of hypoglycemic episodes when using the LGS feature with an insulin delivery shutoff of a maximum of 2 h at a sensor glucose level below 70 mg/dL (3.9 mmol/L). RESULTS: In total, 1,298 LGS alerts occurred (853 shorter than 5 min). Forty-two percent of LGS activations (>5 min) lasted less than 30 min, whereas 24% had a duration of 2 h. The number of hypoglycemic excursions (average/day) was reduced during SAP+LGS (<70 mg/L, 1.27±0.75 vs. 0.95±0.49, P=0.010; ≤40 mg/dL, 0.28±0.18 vs. 0.13±0.14, P=0.005) as was the time spent in hypoglycemia (average minutes/day, 101±68 vs. 58±33, P=0.002) without significant difference in the mean glucose level (145±23 vs. 148±19 mg/dL). No episodes of severe hyperglycemia or diabetic ketoacidosis were observed following LGS activation. CONCLUSIONS: The present investigation provides evidence that SAP with LGS reduces the frequency of hypoglycemia without compromising safety.

PTPN22 1858T allele is associated with younger age at onset of type 1 diabetes and is not related to subsequent thyroid autoimmunity.

To evaluate the prevalence of PTPN22 C1858T polymorphism in young type 1 diabetes patients with or without autoimmune thyroiditis. Genotyping was performed in 209 controls and 243 patients diagnosed with diabetes at median age of 8.6 years. Diabetes-related autoimmunity was assessed at diagnosis of the disease, while thyroid-related autoimmunity was determined at diabetes onset and at annual intervals up to 15 years of follow-up. The 1858T allele frequency was 15.2% in patients and 10.5% in controls (odds ratio 1.53, p = 0.037). 1858T positive patients were significantly younger at diagnosis of diabetes than those without this allele (p = 0.003). No association was found between C1858T polymorphism and diabetes-related autoimmunity (p = 0.173) or thyroid autoimmune disease (p = 0.321), respectively. We conclude that PTPN22 1858T allele is an independent risk factor for type 1 diabetes and associated with younger age at the onset of the disease. However, no association with concomitant thyroid autoimmunity was found.

How do we reduce the number of cases of missed postpartum diabetes in women with recent gestational diabetes mellitus?

OBJECTIVE: Up to 30% of women with recent gestational diabetes mellitus (GDM) remain glucose intolerant after delivery. However, the rate of postpartum oral glucose tolerance tests (ppOGTTs) is low. Our aim in this study was to develop a model for risk assessment to target women with high risk for postpartum diabetes. RESEARCH DESIGN AND METHODS: In 605 Caucasian women with GDM, antenatal obstetrical and glucose data and the glucose data of the ppOGTTs performed 13 weeks (median) after delivery were prospectively collected. RESULTS: A total of 132 (21.8%) women had an abnormal ppOGTT (2.8% impaired fasting glucose, 13.6% impaired glucose tolerance, and 5.5% diabetes). Independent risk factors were BMI >or=30 kg/m(2) (prevalence of abnormal ppOGTT 36.0 vs. 17.3%), gestational age at diagnosis <24 weeks (32.4 vs. 18.0%), 1-h antenatal value >200 mg/dl (11.1 mmol/l) (35.2 vs. 14.8%), and insulin therapy (30.3 vs. 14.5%). The prevalence of an abnormal ppOGTT was assessed according to the number of risk factors: 0, 9.2% (14 of 153); 1, 13.4% (25 of 186); 2, 28.5% (43 of 151); 3, 45.6% (26 of 57); and 4, 68.4% (13 of 19). Subjects were divided according to a significant increase of prevalence and risk for a ppOGTT: low risk (59.9% of subjects), <2 risk factors, 11.6%, odds ratio 1.3; intermediate risk, 2 risk factors, 28.5%, 4.0; and high risk, >2 risk factors, 51.3%, 10.5. The intermediate/high-risk group included 86.6% of those with diabetes and 67% of all those with abnormal ppOGTTs. CONCLUSIONS: Women with >or=2 risk factors have a high risk for an abnormal ppOGTT, and 86% of postpartum diabetes is diagnosed within this group. Targeting women for ppOGTTs based on a risk assessment using available antenatal risk factors might reduce the number of missed cases of postpartum diabetes.

High-dose compared with intermediate-dose methotrexate in children with a first relapse of acute lymphoblastic leukemia.

High-dose methotrexate (MTX) has been extensively used for treatment of acute lymphoblastic leukemia (ALL). To determine the optimal dose of MTX in childhood relapsed ALL, the ALL Relapse Berlin-Frankfurt-Münster (ALL-REZ BFM) Study Group performed this prospective randomized study. A total of 269 children with a first early/late isolated (n = 156) or combined (n = 68) bone marrow or any isolated extramedullary relapse (n = 45) of precursor B-cell (PBC) ALL (excluding very early marrow relapse within 18 months after initial diagnosis) were registered at the ALL-REZ BFM90 trial and randomized to receive methotrexate infusions at either 1 g/m(2) over 36 hours (intermediate dose, ID) or 5 g/m(2) over 24 hours (high dose, HD) during 6 (or 4) intensive polychemotherapy courses. Intensive induction/consolidation therapy was followed by cranial irradiation, and by conventional-dose maintenance therapy. Fifty-five children received stem-cell transplants. At a median follow-up of 14.1 years, the 10-year event-free survival probability was .36 (+/- .04) for the ID group (n = 141), and .38 (+/- .04) for the HD group (n = 128, P = .919). The 2 groups did not differ in terms of prognostic factors and other therapeutic parameters. In conclusion, methotrexate infusions at 5 g/m(2) per 24 hours, compared with 1 g/m(2) per 36 hours, are not associated with increased disease control in relapsed childhood PBC acute lymphoblastic leukemia.