Beata Mianowska

Insulin sensitivity in Type 1 diabetic children and adolescents.

Aim  To estimate insulin sensitivity in Type 1 diabetic children and adolescents, and assess the relationship between insulin sensitivity and clinical markers of adiposity and parameters of the metabolic syndrome.

Efficacy of Metabolic and Psychological Screening for Mood Disorders Among Children With Type 1 Diabetes

OBJECTIVE To compare the diagnostic accuracy and time expenditure of screening models based on glycated hemoglobin (HbA1c) level and psychometric measures for mood disorder (MD) among children with type 1 diabetes. RESEARCH DESIGN AND METHODS With semistructured clinical interviews (Schedule for Affective Disorders and Schizophrenia for Children–Present and Lifetime version, 120 min/patient) as a reference for diagnosing MD, including major depressive disorder (MDD), we tested 163 subjects, aged 8 to 18 years, with type 1 diabetes. We evaluated four screening approaches: 1) Children’s Depression Inventory (CDI) at 30 min/patient, 2) HbA1c level, 3) HbA1c level plus CDI, and 4) HbA1c level plus Childrens Depression Rating Scale (CDRS) at 40 min/patient. These tests were conducted with all participants, and the total time expenditure for all four approaches was calculated as the total time needed to implement successfully the screening for MD or MDD in the center. RESULTS HbA1c performed on par with individual psychometric tests in diagnosing MD or MDD. The HbA1c plus CDRS model was the best screening procedure for both MD and MDD, with diagnostic thresholds for HbA1c established at 8.7% and 9.0%, respectively. Cutoff points for CDRS assessed after filtering by HbA1c were 26 (MD) and 30 (MDD) points. Center-wide application of this procedure would result in an 83% reduction of the examination time necessary for the psychiatrist for MD screening and a 91% reduction for MDD screening, as compared with standard screening with CDI. CONCLUSIONS Use of HbA1c level followed by CDRS is a time-efficient procedure to screen for MD in children with type 1 diabetes.

Immunogenicity of different brands of human insulin and rapid-acting insulin analogs in insulin-naïve children with type 1 diabetes.

Mianowska B, Szadkowska A, Pietrzak I, Zmysłowska A, Wegner O, Tomczonek J, Bodalski J, Młynarski W. Immunogenicity of different brands of human insulin and rapid‐acting insulin analogs in insulin‐naïve children with type 1 diabetes.

Effect of Insulin Dilution on Lowering Glycemic Variability in Pump-Treated Young Children with Inadequately Controlled Type 1 Diabetes.

BACKGROUND We investigated whether in young children with inadequately controlled type 1 diabetes and technical problems with continuous subcutaneous infusion of insulin at 100 units/mL the switch to insulin diluted to 10 units/mL (U10) can limit technical problems and improve glycemic control. SUBJECTS AND METHODS Diluted U10 insulin was started in three children 3.8, 3.2, and 1.3 years old with a hemoglobin A1c (HbA1c) level (mean±SD) of 8.1±0.17% (65±1.7 mmol/mol) and insulin dose of 8.80±2.93 units/day. Patients were evaluated with continuous glucose monitoring (iPro™2; Medtronic Minimed, Northridge, CA) and a quality of life questionnaire (PedsQL™; www.pedsql.org/ ) and surveyed for pump-related problems at baseline and after 3 and 9 months of U10 insulin therapy. RESULTS Continuous glucose monitoring records showed that glycemic variability assessed by SD and M100 decreased significantly (P=0.0085 and P=0.0482, respectively). HbA1c levels dropped to 7.3±1.00% (56±11.0 mmol/mol) after 3 months and to 6.7±0.55% (50±6.1 mmol/mol) after 9 months (P=0.12). Technical difficulties were minimized. CONCLUSIONS These results suggest that the use of U10 insulin decreases glycemic variability and improves hampered pump therapy in young children with inadequately controlled type 1 diabetes.

Gender and Age – Dependent effect of type 1 diabetes on obesity and altered body composition in young adults

INTRODUCTION AND OBJECTIVE The aim of the study was to evaluate the influence of age and gender on the prevalence of overweight and obesity, body composition and fatty tissue distribution in young adults with type 1 diabetes. MATERIAL AND METHODS 197 patients with type 1 diabetes aged 20-40 years participated in the study. The control group consisted of 138 healthy adults. Body weight, height, waist and hip circumferences were measured. Analysis of body mass composition was performed using the bioimpedance. Study groups were stratified into cohorts aged <30 and 30+ years. RESULTS Overweight and obesity were diagnosed in 35.5% and 13.2% of diabetic patients and in 26.1% and 7.3% of the control group, respectively (p=0.016). In the whole study group, advanced age (OR=1.10; p<0.001) and diabetes mellitus (OR=2.25; p=0.001) predisposed patients to excess body weight. Women had a lower prevalence of overweight and obesity, but a trend toward excessive body mass was observed in diabetic females (OR=1.18; p=0.181). Diabetic females more often had abdominal obesity than control females (mean difference - 19.2%; p=0.020). Higher total body fat mass was found in the diabetic group (p=0.037). Diabetic females had a higher amount of absolute (p<0.001) and relative body fat mass (p=0.002), fat free mass (p=0.007), relative arm (p=0.007), leg (0<0.001) and trunk (p-=0.006) fat mass than control females. Diabetic males showed only higher relative fat mass of the lower limbs compared to control males (p=0.018). CONCLUSIONS Patients with type 1 diabetes develop overweight and obesity in early adulthood more frequently than the general population and are characterized by higher body fat mass. Gender-related differences in body weight and composition in young type 1 diabetic adults were found.

Bilirubin is an independent factor inversely associated with glycated hemoglobin level in pediatric patients with type 1 diabetes.

Bilirubin is a potent antioxidant, and serum total bilirubin (STB) concentrations correlate negatively with cardiovascular risk. In adult diabetic patients and in healthy adults, a negative correlation between STB and glycated hemoglobin (HbA1c) has been reported. We investigated whether there is such an association in children and adolescents with type 1 diabetes mellitus.

Hypoglycemia and glycemic variability among children with acute lymphoblastic leukemia during maintenance therapy

Symptomatic, chemotherapy-related hypoglycemia is a rare complication associated with the administration of purine analogs. The aim of the study was to evaluate 24 h glucose variability and frequency of hypoglycemia among patients with acute lymphoblastic leukemia (ALL) during maintenance therapy (MT). Eighteen children with ALL underwent continuous glucose monitoring (CGM). The number of episodes of hypoglycemia and glucose variability were analyzed. Serum alanine aminotransferase, asparagine aminotransferase, and γ-glutamyl transferase levels were measured as liver function markers. The mean glucose level in CGM equaled 105 ± 13 mg/dL, with standard deviation (SD) 13.8 ± 6.1 mg/dL, and the mean amplitude of glycemic excursions (MAGE) equaled 44.7 ± 19.9 mg/dL. Eight patients had at least one measurement below 70 mg/dL while four patients had measurements below 50 mg/dL. Children with hypoglycemia in CGM examination had a lower median body mass index standard deviation score (BMI Z-score) (−0.65 [−0.94 to −0.27] vs. −0.14 [−0.29 to 0.35]; p = 0.05) and shorter duration of MT (6.5 [4–15] vs. 22.5 [16.5–28] weeks; p = 0.004). Glucose variability parameters were strongly correlated with BMI Z-score and liver function enzymes. Hypoglycemia, particularly at night-time, may develop as a complication of MT in children with ALL. The risk factors for low glucose level are low BMI Z-score and initiation of MT.

Use of lispro insulin diluted with normal saline to 10 U/ml in an insulin pump: case report.

In very young children with type 1 diabetes mellitus (T1DM), insulin dose is often below 5–10 U/day, which necessitates infusion of volumes lower than 0.05–0.1 ml/day of 100 U/ml insulin. Some children require as little as 0.2–0.3 U of bolus insulin (0.002–0.003 ml of 100 U/ml) to cover 10 g of meal carbohydrates. These factors pose a challenge for precise and stable continuous subcutaneous insulin delivery as well as for occlusion alarm triggering in insulin pumps. As T1DM diagnosis is made at an increasingly younger age, the problem of low dose delivery may concern more and more patients.1 Lispro insulin diluted with a dedicated diluent has been used in neonates or young children on pump therapy.2–4 We present our first experience with 10 U/ml lispro diluted in normal saline used in an insulin pump. A 2.5-year-old boy with a 12-month history of T1DM had been on pump therapy since diagnosis [Paradigm 722®, Quick-set® 6 mm, Medtronic MiniMed, Northridge, CA; aspart (NovoRapid®, Novo Nordisk A/S, Bagsvaerd, Denmark) followed by lispro (Humalog®, Eli Lilly Nederland B.V., Houten, The Netherlands)]. He was a poor eater, and his weight and height were <3rd percentile for age and sex. His glycated hemoglobin A1c (HbA1c) levels were 6.4–6.7%; however, removal of air bubbles from the tubing was necessary several times per week, cannula occlusions were frequent, and technical problems made it difficult to use the infusion sets for more than 2 days. Blood glucose (BG) fluctuations were high (mean ± standard deviation, 173 ± 92.6 mg/dl; 10–17 BG measurements per day). Insulin dose equaled ˜4.0–6.5 U/day (0.41–0.62 U/kg/day), with ˜18–25% given as a basal rate (most 0.05 U/h, selected hours 0.00 U/h). Steel infusion sets were tried without improvement. In addition to dedicated insulin diluents not being readily accessible, the patient’s bilirubin and biliary acids were temporarily elevated, which potentially could make him more vulnerable to preservatives (i.e., metacresol/phenol). Therefore, we decided to try insulin diluted in normal saline. The Local Ethics Committee approved this modification of therapy, and the parents signed informed consent. After detailed instructions were given concerning insulin dilution and pump settings (settings 10 times higher than actual insulin doses), the parents started to use 10 U/ml dilution of lispro in normal saline on an outpatient basis. Infusion sets were changed, and a new 10 U/ml lispro dilution was prepared every 3 days. During the first days of 10 U/ml lispro therapy, technical problems with insulin delivery subsided and BG levels became lower and more predictable (average BG, 138 ± 70.8 mg/dl; 13–14 measurements per day; Figure 1). Throughout the 20-month-long follow-up, tubing/cannula occlusion was suspected only three times. One episode of severe hypoglycemia necessitating glucagon injection occurred (BG 22 mg/dl), manifesting in impaired consciousness for 2–3 min, without seizures. His HbA1c levels equaled 6.3–6.9% during the first 15 months but increased to 7.3–7.5% during the last 5 months of follow-up (when respiratory tract infections recurred). Insulin dose on 10 U/ml lispro equaled from 4.6 to 2.8 U/day (0.37–0.20 U/kg/day), with percentage of basal rate ˜35–55%, depending on infections and appetite. The boy is still an unpredictable, extremely poor eater, which unfavorably affects his glucose control, but he has developed well and has caught up in weight (at 3rd percentile) and height (at 10th percentile). Bilirubin and biliary acids decreased to normal. As technical problems with insulin delivery were definitely minimized, the parents are satisfied with this modification of insulin therapy, and they opposed a switch back to 100 U/ml. Figure 1 Blood glucose levels recorded in the patient’s BG meter during the week of switch from 100 U/ml lispro to 10 U/ml lispro in the insulin pump (the arrow shows the time of the switch). Despite this case report being rather anecdotic, this revealed important clinical implications. We suggest that the 10 U/ml dilution of lispro in an insulin pump may help to overcome technical problems with continuous insulin delivery, and this treatment seemed to be safe in our reported child who required a very low insulin dose. Strict parental cooperation and careful supervision of the child is crucial during such therapy. Insulin pump software allowing setting actual doses for diluted insulin could facilitate its use in young children. Insulin dilution could be considered in the development of “closed-loop” insulin delivery systems for the youngest age group. Further studies and input from insulin manufacturers are needed to draw final conclusions.

Fetal hemoglobin and hemoglobin A1c level among pediatric patients with type 1 diabetes

INTRODUCTION Glycated hemoglobin (HbA1c) is used as a cumulative estimate of mean blood glucose levels from the preceding 5-12 weeks. This is the gold standard in assessing glycemic control in patients with diabetes. The ADA criteria for the diagnosis of diabetes, including HbA1c level, contribute to the importance of recognizing any variation pertaining to the HbA1c measurement. HbA1c is often used as a primary endpoint in the interventional studies among patients with diabetes. Thus, knowledge about factors independently to glycemia, affecting HbA1c is clinically useful. AIM OF STUDY Evaluation variability of fetal hemoglobin (HbF) level among Polish children with diabetes and how it may affect the HbA1c level measurement. MATERIAL AND METHODS This was a prospective cohort study. A laboratory HbA1c testing was performed for more than 96% of pediatric diabetic patients in the region. In our study we included all consecutive patients aged 2 to 18 years with type 1 diabetes (T1D) and the disease duration longer than one year (555 patients). All patients had HbA1c and HbF measured at three time-points during minimum one-year period. In the same time, clinical data were recorded. The measurements of HbA1c and HbF were performed by means of cation-exchange high-pressure liquid chromatography (HPLC) on a D-10 Dual A2/F/A1c (Bio-Rad Laboratories, Hercules, CA, USA). Statistical analysis was performed using the Statistica 10.0 package (StatSoft, Tulsa, USA). RESULTS An average age in the observed group was 12.9±3.8 years, diabetes duration 5.6±3.4 years, HbA1c was 7.59±1.33% (59±10.65 mmol/mol). In 78 (14%) patients elevated levels of HbF (>0.8%) were found at each time-point, mean value 1.2±0.45%. Elevated HbF was associated with younger age at examination (p=0.03) and younger age of diagnosis (p=0.01). It was not related to diabetes duration (p=0.21). No correlation between HbA1c and HbF was observed in the study (R=-0.09; p=0.43). CONCLUSIONS Fetal hemoglobin does not affect HbA1c measurement among pediatric patients with type 1 diabetes older that 2 years.

Arterial Stiffness, BMI, Dipping Status and ACE D/I Polymorphism in Type 1 Diabetic Children.

THE AIM of the study was to investigate clinical and genetic determinants of arterial stiffness in children and adolescents with type 1 diabetes mellitus. MATERIAL AND METHODS 122 patients (mean age: 16.0±2.35 years), with an average diabetes duration of 5.0 years and without evidence of arterial hypertension were recruited. Ambulatory arterial stiffness index (AASI) was assessed with 24-h automatic blood pressure monitoring. Body weight, height, HbA1c and plasma lipids were measured. Angiotensin I converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism was analysed. RESULTS Mean AASI equalled 0.22±0.20 and showed significant, positive correlation with age and BMI-SDS. No association was found between AASI and gender, diabetes duration, daily insulin dose, HbA1c and blood lipids concentration. AASI was higher in non-dippers compared to dippers (0.26±0.18 vs. 0.19±0.18, respectively; p=0.04). In a multivariate model AASI was significantly associated with II homozygosity of ACE gene (p=0.007). CONCLUSIONS In type 1 diabetic children and adolescents AASI is correlated with age and BMI-SDS. Non-dipping status and I-allele were associated with higher arterial stiffness.