Influence of plasma glucagon levels on glycemic control in children with type 1 diabetes

Objective: The aim of this study was to investigate the association between plasma glucose (PG), HbA1c and plasma glucagons levels in children with type 1 diabetes to determine the influence of plasma glucagon on their glycemic control. Methods: The study was conducted in 60 Japanese children, aged 13.3 ± 4.6 years, with type 1 diabetes for at least 3 years of diabetes. Most of the subjects had absent pancreatic β‐cell function. We compared the glucagon levels among patient groups stratified according to the 2‐hour postprandial levels (<50, 50–99, 100–199, 200–299, and ≥300 mg/dL), and the HbA1c levels (<7.0, 7.0–7.9, 8.0–8.9, and ≥9%). Results: The mean 2‐hour postprandial PG, HbA1c and plasma glucagon levels were 174 ± 97 mg/dL, 7.7 ± 1.3% and 84.0 ± 32.6 pg/mL, respectively. The glucagon levels were highly correlated with the PG levels (r = 0.553, P < 0.0001) and mildly correlated with the HbA1c levels (r = 0.301, P = 0.0192). Patients with high PG levels had significantly higher levels of glucagon as compared with those with lower PG levels (139.4 ± 47.2, 78.4 ± 17.3, 82.4 ± 21.0, 98.3 ± 29.2 and 93.8 ± 18.3 pg/mL, P = 0.0009). On the other hand, there were no significant differences in plasma glucagon levels among patient groups stratified according to HbA1c levels (P = 0.1566), however, patients with HbA1c levels ≥ 9% had significantly higher levels of glucagon than those with HbA1c levels < 7% (113.3 ± 53.4 vs 80.8 ± 18.4 pg/mL, P = 0.0291). Conclusion: These results suggest that patients with high PG are likely to have high concentrations of plasma glucagon, which may aggravate glycemic control progressively, leading to elevation of HbA1c levels.     

Impact of exercise on overnight glycemic control in children with type 1 diabetes mellitus

OBJECTIVE: To examine the effect of exercise on overnight hypoglycemia in children with type 1 diabetes mellitus (T1DM). STUDY DESIGN: At 5 clinical sites, 50 subjects with T1DM (age 11 to 17 years) were studied in a clinical research center on 2 separate days. One day included an afternoon exercise session on a treadmill. On both days, frequently sampled blood glucose levels were measured at the DirecNet central laboratory. Insulin doses were similar on both days. RESULTS: During exercise, plasma glucose levels fell in almost all subjects; 11 (22%) developed hypoglycemia. Mean glucose level from 10 pm to 6 am was lower on the exercise day than on the sedentary day (131 vs 154 mg/dL; P=.003). Hypoglycemia developed overnight more often on the exercise nights than on the sedentary nights (P=.009), occurring on the exercise night only in 13 (26%), on the sedentary night only in 3 (6%), on both nights in 11 (22%), and on neither night in 23 (46%). Hypoglycemia was unusual on the sedentary night if the pre-bedtime snack glucose level was>130 mg/dL. CONCLUSIONS: These findings indicate that overnight hypoglycemia after exercise is common in children with T1DM and support the importance of modifying diabetes management after afternoon exercise to reduce the risk of hypoglycemia.     

应用胰岛素泵治疗儿童及青少年1型糖尿病对糖代谢的影响

为观察应用胰岛素泵治疗儿童及青少年1型糖尿病(T1DM)对糖代谢的影响 ,随访10例胰岛素泵治疗的T1DM患儿 ,分别观察胰岛素泵治疗前、后6个月的糖化血红蛋白值(HbA1c)、胰岛素用量、严重低血糖及酮症酸中毒发生次数的变化情况。结果显示 ,胰岛素泵治疗6个月后HbA1c 显著下降 ,治疗前为8.97 %±1.69 %,治疗后为7.51 %±1.17 % (t=2.52 ,P<0.05) ;胰岛素用量无显著下降 ;未发生严重低血糖和酮症酸中毒。表明胰岛素泵治疗可有效控制血糖 ,明显降低HbA1c,减少低血糖及酮症酸中毒的发生 ,是儿童及青少年T1DM常规治疗的较好选择。     

Frequency of SMBG correlates with HbA1c and acute complications in children and adolescents with type 1 diabetes

Ziegler R, Heidtmann B, Hilgard D, Hofer S, Rosenbauer J, Holl R; for the DPV‐Wiss‐Initiative. Frequency of SMBG correlates with HbA1c and acute complications in children and adolescents with type 1 diabetes. The aim of this study was to correlate the frequency of self‐monitoring of blood glucose (SMBG) to the quality of metabolic control as measured by hemoglobin A1c (HbA1c), the frequency of hypoglycemia and ketoacidosis, and to see whether the associations between SMBG and these outcomes are influenced by the patient's age or treatment regime. We analyzed data from the DPV‐Wiss‐database of 26 723 children and adolescents aged 0–18 yr with type 1 diabetes recorded during 1995–2006. Variables evaluated were gender, age at visit, diabetes duration, therapy regime, insulin dose, body mass index–standard deviation scores (BMI–SDS), HbA1c, rate of hypoglycemia, and ketoacidosis. In the youngest age group of children under the age of 6 yr, the frequency of SMBG was the highest compared with that in children aged 6–12 yr or children aged > 12 yr: 6.0/d vs. 5.3/d vs. 4.4/d (p < 0.001). Frequency of SMBG differed significantly also in the different groups of treatment (p < 0.001), but only for the continuous subcutaneous insulin infusion (CSII) group the frequency was considerably higher: 5.3/d (CSII) vs. 4.7/d (multiple daily injections) vs. 4.6/d (conventional therapy). Adjusted for age, gender, diabetes duration, year of treatment, insulin regimen, insulin dose, BMI‐SDS, and center difference, SMBG frequency was significantly associated with better metabolic control with a drop of HbA1c of 0.20% for one additional SMBG per day (p < 0.001). Increasing the SMBG frequency above 5/d did not result in further improvement of metabolic control. A higher frequency of SMBG measurements was related to better metabolic control. But only among adolescents aged > 12 yr, metabolic control (HbA1c) improved distinctively with two or more blood glucose measurements.     

Associations between physical activity, sedentary behavior, and glycemic control in a large cohort of adolescents with type 1 diabetes: the Hvidoere Study Group on Childhood Diabetes

Background: The Hvidoere Study Group on Childhood Diabetes has demonstrated persistent differences in metabolic outcomes between pediatric diabetes centers. These differences cannot be accounted for by differences in demographic, medical, or treatment variables. Therefore, we sought to explore whether differences in physical activity or sedentary behavior could explain the variation in metabolic outcomes between centers. Methods: An observational cross‐sectional international study in 21 centers, with demographic and clinical data obtained by questionnaire from participants. Hemoglobin A1c (HbA1c) levels were assayed in one central laboratory. All individuals with diabetes aged 11–18 yr (49.4% female), with duration of diabetes of at least 1 yr, were invited to participate. Individuals completed a self‐reported measure of quality of life (Diabetes Quality of Life ‐ Short Form [DQOL‐SF]), with well‐being and leisure time activity assessed using measures developed by Health Behaviour in School Children WHO Project. Results: Older participants (p < 0.001) and females (p < 0.001) reported less physical activity. Physical activity was associated with positive health perception (p < 0.001) but not with glycemic control, body mass index, frequency of hypoglycemia, or diabetic ketoacidosis. The more time spent on the computer (r = 0.06; p < 0.05) and less time spent doing school homework (r = ?0.09; p < 0.001) were associated with higher HbA1c. Between centers, there were significant differences in reported physical activity (p < 0.001) and sedentary behavior (p < 0.001), but these differences did not account for center differences in metabolic control. Conclusions: Physical activity is strongly associated with psychological well‐being but has weak associations with metabolic control. Leisure time activity is associated with individual differences in HbA1c but not with intercenter differences.     

Basal insulin switch from NPH to glargine in children and adolescents with type 1 diabetes

Background:  Insulin glargine is a long-acting insulin analogue increasingly used instead of neutral protamine Hagedorn (NPH) insulin in young subjects with type 1 diabetes.
Objective:  We evaluated the clinical course of diabetes in children and adolescents who were switched from NPH to insulin glargine.
Methods:  Between August 2003 and November 2004, a total of 76 subjects were switched to glargine in our clinic, treating 340 children with type 1 diabetes. All the subjects had been receiving insulin NPH, and their serum C-peptide levels had been non-detectable for at least 1 yr. Data were collected retrospectively, and 12–18 months after the change, experiences with glargine were inquired using a questionnaire. Seven subjects (9.2%) discontinued glargine before 12 months, and seven refused to participate.
Results:  Data for 62 subjects were analyzed. At the switch (0 months), their mean age was 12.7 yr (range 5.1–17.5), mean duration of diabetes was 6.7 yr (range 1.8–14.3), and mean hemoglobin A1c was (HbA1c) 9.2%. Twelve months later (+12 months), the mean HbA1c remained similar (9.2%), the proportion of long-acting insulin was smaller (47.7 vs. 58.1%; p < 0.001), and the daily insulin dose was lower (0.97 vs. 1.05 IU/kg; p < 0.001). The number of injections was lower at +12 months (17.7% with more than five injections vs. 64.5%; p < 0.001). No differences were seen in weight for height or the number of severe hypoglycemias. Most subjects who continued with glargine for ≥12 months considered glargine better than NPH.
Conclusions:  A switch to insulin glargine retains a similar glycemic control and does not change the number of severe hypoglycemias.     

Continuous subcutaneous insulin infusion vs. multiple daily injections in children with type 1 diabetes: a systematic review and meta-analysis of randomized control trials

Objective:  To investigate potential effects of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) on glycemic control in children with type 1 diabetes mellitus (T1DM).
Study design:  Meta-analysis and systematic review of randomized control studies (RCTs). The electronic databases MEDLINE, Cochrane Library, and EMBASE were searched through October 2007.
Results:  Six RCTs involving 165 participants with T1DM met our predefined inclusion criteria. Combined data from all trials showed that the CSII group compared with the MDI group experienced a significant reduction in the level of glycosylated hemoglobin. The pooled weighted mean difference (WMD) was −0.24% [95% confidence interval (95% CI) −0.41 to −0.07, p < 0.001] with a fixed model and remained significant in the random effect model. This effect was reached by slightly decreasing insulin requirement [three RCTs, n = 74, WMD −0.22 IU/kg/d (95% CI −0.31 to −0.14, p < 0.001)]. No differences in the incidences of ketoacidosis and severe hypoglycemic events were found.
Conclusions:  In short-term insulin therapy, CSII compared with MDI is a more effective form of metabolic control and allows reducing the daily insulin requirement. Yet, no conclusions have been made so far whether this effect holds in later years. These results should be approached with caution because of the methodological limitations of the analyzed studies.     

Application of novel dual wave meal bolus and its impact on glycated hemoglobin A1c level in children with type 1 diabetes

Background: An insulin pump is an advanced technology offering new options of bolus – normal (N), dual wave (D-W) or square wave (S-W) bolus to deliver mealtime insulin.
Objectives: To assess the impact of D-W/S-W boluses on metabolic control (glycated haemoglobin A1c, HbA1c) and to estimate the paediatric patients compliance with implementation of this system in daily practice.
Methods: The cross-sectional study included 499 records of patients aged 0–18 yr. Data from the insulin pump memory provided information on the number of D-W/S-W boluses during a 2-wk period, the insulin requirement (U/kg/d) and the percentage of basal insulin. The HbA1c value (%) and the patient's weight were determined during medical examinations. Mealtime dose of insulin in D-W/S-W bolus was calculated based on the amount of carbohydrate and fat/protein products.
Results: The number of applied D-W/S-W boluses was 16.6 ± 0.77/14 d (ranged 0–95), while 18.8% of patients did not program D-W/S-W boluses. The lowest HbA1c value was found in the group using two and/or more D-W/S-W boluses per day (p = 0.001) compared with the group administrating less than one D-W/S-W bolus/d. Patients with HbA1c level <7.5% had a statistically higher relevant number of D-W/S-W boluses, 19.55 (95% CI: 17.44–21.65) vs. 12.42 (95% CI: 10.22–14.61) (p < 0.001), while there was no correlation between the number of boluses and HbA1c in patients in the remission phase (<0.5 IU/kg/d) (r = 0.012, p = 0.930).
Conclusions: Patients using at least one D-W/S-W bolus per day achieved a recommended level of HbA1c. Paediatric patients with type 1 diabetes mellitus were found to be able to apply D-W/S-W boluses in daily self-treatment process based on food counting.     

Electrogastrography in children and adolescents with type 1 diabetes: weak correlation with metabolic control parameters

AIM: To evaluate gastric myoelectrical activity with respect to duration and metabolic control of type 1 diabetes mellitus (T1DM). METHODS: 172 children and adolescents with T1DM (mean 14.4+/-3.7 y), divided into subgroups depending on diabetes duration (< 5 and > 5 y), and 35 healthy controls (mean 13.93+/-3.59 y) were examined. All subjects underwent electrogastrography (EGG) performed after overnight fasting. In subjects with T1DM, haemoglobin A1c (HbA1c) and blood glucose levels during EGG records were measured. RESULTS: 15.69% of T1DM patients and 91.42% of the controls fulfilled normal EGG criteria (p < 0.001). T1DM subjects had a lower percentage of fasting normogastria (34.56+/-27.35% vs 69.84+/-18.16%, p = 0.0001) and higher bradygastria (51.97+/-30.24% vs 19.11+/-15.01%, p = 0.0001) compared to controls. In diabetic patients, an increase in postprandial normogastria (60.37+/-23.96% vs 76.68+/-12.38, p < 0.05) and a decrease in bradygastria percentage (25.67+/-21.01% vs 9.58+/-7.13%, p < 0.05) was observed. In children with disease < 5 y, diabetes duration correlated with power ratio (r = - 0.27, p = 0.01), postprandial normogastria (r = - 0.24, p = 0.03) and tachygastria (r = 0.25, p = 0.02). Weak correlations between EGG parameters and glucose (preprandial dominant frequency r = - 0.19, p < 0.05; postprandial normogastria r = 0.23, p < 0.01) and HbA1c levels (preprandial bradygastria r = 0.19, postprandial dominant power r = 0.23; p < 0.05) were observed. CONCLUSION: Gastric myoelectrical rhythm derangement is present in a large proportion of young diabetic patients. Bradygastria is the most prominent EGG abnormality. Weak correlation was found between EGG parameters and diabetes metabolic control.