Intravenous glucagon in a deliberate insulin overdose in an adolescent with type 1 diabetes mellitus

Massive insulin overdose may be associated with unpredictable and prolonged hypoglycemia. Concerns surrounding the potential provocation of insulin release from beta cells have previously prevented the use of intravenous glucagon as an adjunct to infusion of dextrose in this situation. We describe the case of a 15‐yr‐old boy with type 1 diabetes mellitus (T1DM) who presented with profound hypoglycemia following an overdose of an unknown quantity of premixed insulin. Owing to an increasing dextrose requirement and a dependence on hourly intramuscular glucagon injections, a continuous intravenous infusion of glucagon was commenced which successfully avoided the requirement for central venous access or concentrated dextrose infusion. Nausea was managed with anti‐emetics. Intramuscular and subcutaneous glucagon is effective in the management of refractory and severe hypoglycemia in youth with both T1DM and hyperinsulinism. Concerns regarding the precipitation of rebound hypoglycemia with the use of intravenous glucagon do not relate to those with T1DM. This treatment option may be a useful adjunct in the management of insulin overdose in youth with T1DM and may avoid the requirement for invasive central venous access placement.     

Impaired overnight counterregulatory hormone responses to spontaneous hypoglycemia in children with type 1 diabetes

Abstract:  To assess the changes in counterregulatory hormones overnight after an afternoon of structured exercise or sedentary activity in children with type 1 diabetes mellitus (T1DM), the Diabetes Research in Children Network (DirecNet) studied 50 children (10 to <18 yr) with T1DM in five clinical research centers on two separate days (with and without an afternoon exercise session) using a crossover design. Glucose, epinephrine, norepinephrine, cortisol, growth hormone (GH), and glucagon concentrations were measured hourly overnight. Nocturnal hypoglycemia [plasma glucose concentrations ≤70 mg/dL (3.9 mmol/L)] occurred more frequently on the nights following exercise (56 vs. 36%; p = 0.008). Mean hourly concentrations of most hormones did not differ between sedentary or exercise nights or between nights with or without hypoglycemia. Spontaneous nocturnal hypoglycemia only stimulated small increases in plasma epinephrine and GH concentrations and failed to cause a rise in norepinephrine, cortisol, or glucagon levels in comparison with values during the hour before or after hypoglycemia or other times during those same nights. Counterregulatory hormone responses to spontaneous nocturnal hypoglycemia were markedly decreased regardless of whether there was antecedent afternoon exercise in children with T1DM. Sleep-induced impairments in counterregulatory hormone responses likely contribute to the increased risk of hypoglycemia during the entire overnight period in youth with T1DM.     

The effectiveness of glucose,sucrose, and fructose in treating hypoglycemia in children with type 1 diabetes

Husband AC, Crawford S, McCoy LA, Pacaud D. The effectiveness of glucose, sucrose, and fructose in treating hypoglycemia in children with type 1 diabetes. Objective: There is a lack of evidence regarding the most effective treatment option for managing naturally occurring hypoglycemia in children with type 1 diabetes. The objectives of this study were (i) to determine if sucrose and fructose are equally effective as glucose in the treatment of spontaneous hypoglycemia in children with type 1 diabetes; and (ii) to determine prestudy and poststudy hypoglycemia treatment preferences. Methods: Thirty‐three subjects [aged 5.4–15.5 yr and average duration of type 1 diabetes of 3.1 yr (SD = 2.3)] participated in a randomized, crossover design. The main outcome was the effectiveness of treatment as defined by a blood glucose meter reading that was ≥ 4.0 mmol/L 15 min after treatment. Each subject treated five hypoglycemic events with each treatment type: glucose (BD Glucose Tablets?), sucrose (Skittles?), and fructose (Fruit to Go?). Results: There was a significant difference between the effectiveness of the three treatments [Wilk's Lambda F(2,28) = 8.64, p = 0.001]. No significant difference between treatment with glucose and treatment with sucrose was noted, but the treatment effectiveness for fructose was significantly lower than sucrose [F (1,29) = 16.09, p < 0.001] and glucose [F (1,29) = 15.64, p < 0.001]. The preferred treatment choices before the study were as follows: 36% glucose, 18% sucrose, and 33% fructose sources. Poststudy, 52% of children preferred the same treatment, which was effective (glucose or sucrose), followed by 35% who changed their preference to an effective treatment. Conclusion: Skittles? are as effective in treating hypoglycemia as more expensive BD Glucose Tablets? in children with type 1 diabetes.     

Mini-dose glucagon rescue for mild hypoglycaemia in children with type 1 diabetes: the Brisbane experience

OBJECTIVES: To evaluate the use of small doses of glucagon using an insulin syringe in mild or impending hypoglycaemia in children with type 1 diabetes. METHODS: Data were collected from patients attending the Paediatric Diabetes Clinic at the Queensland Diabetes Centre at the Mater Hospital, Brisbane in 2002-2004 following the institution of a new protocol for home management of mild or impending hypoglycaemia associated with inability or refusal to take oral carbohydrate. The protocol recommended the use of subcutaneous injections of glucagon using insulin syringes at a dose of two 'units' (20 microg) in children 2 years of age or younger, and for older children one unit per year of age up to a maximum of 15 units (150 microg), with an additional doubled dose given if the blood glucose had not increased in 20 min. RESULTS: Over a 2-year period, 25 children were treated with mini-dose glucagon on a total of 38 occasions. Additional doses were required for recurring hypoglycaemia on 20 (53%) occasions. The child could be managed at home on 32 (84%) of these 38 occasions, with only 6 (16%) children needing hospital treatment. CONCLUSIONS: Our study confirmed that small doses of glucagon given subcutaneously with an insulin syringe is a simple, practical and effective home treatment of mild or impending hypoglycaemia due to gastroenteritis or food refusal in children with type 1 diabetes.     

Variables associated with severe hypoglycemia in children and adolescents with type 1 diabetes: a population‐based study

Blasetti A, Di Giulio C, Tocco AM, Verrotti A, Tumini S, Chiarelli F, Altobelli E. Variables associated with severe hypoglycemia in children and adolescents with type 1 diabetes: a population‐based study. Objective: Hypoglycemia remains a central problem in the management of type 1 diabetes mellitus (T1DM) and limits the achievement of good or normal glycemic control. The Diabetes Control and Complication Trial showed that intensive treatment of T1DM increased the risk of severe hypoglycemia (SH) when compared to conventional therapy. The aim of our study was to determine the incidence of SH and associated variables in a population of children and adolescents with T1DM. Research design and methods: We performed a 7.5‐yr prospective study enrolling 195 patients aged 13.9 ± 6.6 yr. The study was carried out by referring to the T1DM population‐based register in the Abruzzo region of Italy. The incidence of SH, defined as blood glucose levels <50 mg/dL (<2.77 mmol/L) associated with altered states of consciousness (including confusional state, seizures, and coma) was recorded. Glycated hemoglobin (HbA1c) percentage, insulin dose, insulin regimen, time since diagnosis, and age at onset were also recorded. Results: One hundred and thirty‐three severe hypoglycemic events occurred during the study period; the overall incidence was 9.4 episodes per 100 patient‐years. Significant predictors of hypoglycemia were diabetes duration >10 yr (p = 0.01), basal/bolus insulin ratio (ratio of daily basal insulin units to daily bolus insulin units) >0.8 (p = 0.01). No relationship was found between hypoglycemic episodes and HbA1c levels, daily insulin requirements, or insulin regimen. Conclusions: In these patients, a relatively low incidence of SH was recorded, without pronounced association with lower HbA1c or multiple daily injection insulin therapy. SH seems to be mainly related to management of diabetes. We believe that the main path to SH prevention is through patient and family education in the management of T1DM.     

不同病程的1型糖尿病患儿血清细胞因子的变化

目的　了解不同病程的 1型糖尿患儿血清细胞因子的变化。方法　第 1组为新诊断 1型糖尿病患儿 2 6例。第 2组为病程 >3年、长期治疗不伴其他疾病的 1型糖尿病 2 0例。第 3组 :因身材矮小但无慢性疾病的患儿为正常对照组 30例。以放射免疫分析法 (RIA)或酶联免疫吸附法 (ELISA)法检测血清白细胞介素(IL) 1β、2、4、12 ,肿瘤坏死因子 α(TNF α) ,干扰素 γ(IFN γ)水平 ,计算Th1、Th2来源细胞因子比值。 结果　第1组IL 1β较第 3组显著增高 ,第 2组IL 1β水平下降 ;第 1、2组IL 4水平低于第 3组 ,第 1、2组间IL 4比较无显著性差异。第 1、2组IL 2 /IL 4、IFN γ/IL 4较第 3组升高 ;第 1、2组比较无显著差异。第 1组IL 2明显低于第 3组 ,第 2组IL 2明显增高。IL 12、IFN γ和TNF α水平于各组间均无显著差异。结论　 1.IL 1β、IL 2水平与病程有关。 2 .IFN γ/IL 4、IL 12 /IL 4未随病程延长而改变 ,以Th1来源的细胞因子占优势 ,提示糖尿病患儿免疫系统本身存在Th1优势的倾向     

A prospective study of severe hypoglycemia and long-term spatial memory in children with type 1 diabetes

In a previous retrospective study, severe hypoglycemia (SH) was associated with decreased long-term spatial memory in children with type 1 diabetes mellitus (T1DM). In this study, we tested the hypothesis that prospectively ascertained SH would also be associated with decreased spatial long-term memory over time. Children with T1DM (n = 42) and sibling controls (n = 25) performed a spatial delayed response (SDR) task with short and long delays and other neuropsychological tests at baseline and after 15 months of monitoring. Extreme glycemic events and other medical complications were recorded prospectively during follow-up. Fourteen T1DM children experienced at least one episode of SH during the follow-up period (range = 1-5). After controlling for long-delay SDR performance at baseline, age, gender, and age of onset, the presence of SH during the prospective period was statistically associated with decreased long-delay SDR performance at follow-up (semipartial r = -0.38, p = 0.017). This relationship was not seen with short-delay SDR or with verbal or object memory, attention, or motor speed. These results, together with previously reported data, support the hypothesis that SH has specific, negative effects on spatial memory skills in T1DM children.     

Bilateral metabolic cataracts in 10-yr-old boy with newly diagnosed type 1 diabetes mellitus

Abstract:  Classic symptoms of diabetes mellitus in childhood prompting parents to seek medical attention include polydipsia, polyuria, polyphagia, weight loss and kussmal breathing. Cataracts with juvenile diabetes usually occur in patients with long-standing, poorly controlled diabetes (1, 2) . We describe a child in whom the acute loss of vision secondary to lenticular opacities was the initial sign of insulin-dependent diabetes mellitus.     

Insulin resistance in children and adolescents with type 1 diabetes mellitus: relation to obesity

BACKGROUND: Insulin resistance is well recognized both in type 1 diabetes mellitus (T1DM) and in obesity. Studies concerning the relation between insulin resistance and overweight in T1DM have not yet been carried out. METHODS: Degree of overweight [standard deviation score-body mass index (SDS-BMI)] and daily insulin doses per weight (ID/kg), per body surface (ID/m2), and per ideal body weight (ID/IW) were recorded in 4124 children aged between 5 and 20 yr with a duration of T1DM of 4-5 yr and an adequate metabolic control [hemoglobin A1c (HbA1c) <8.0%]. SDS-BMI was compared between insulin-resistant (ID/kg > or = 1.0) and insulin-sensitive (ID/kg <1.0) children. The ID/kg, ID/m2, and ID/IW were compared between obese (SDS-BMI >1.9) and non-obese children. Multivariate linear regression analysis was conducted for the dependent variables ID/kg, ID/m2, and ID/IW, including age, gender, SDS-BMI, and HbA1c as independent variables. RESULTS: The 882 insulin-resistant children did not differ significantly (p = 0.447) with respect to SDS-BMI (median +0.38) compared to the 3242 insulin-sensitive children (median SDS-BMI +0.42). The ID/kg was significantly (p = 0.031) lower in the obese children compared to the non-obese children (median 0.80 vs. 0.83), while ID/m2 (median 31.0 vs. 26.2) and ID/IW (median 1.17 vs. 0.85) were significantly (p < 0.001) increased in the obese children. In multivariate linear regression analysis, SDS-BMI was significantly (p < 0.001) associated with an increase in ID/m2 and ID/IW and a decrease in ID/kg. CONCLUSIONS: T1DM children with insulin resistance based on ID/kg are not more overweight than insulin-sensitive children with T1DM. ID/m2 and ID/IW seem to reflect a better tool than ID/kg to describe the influence of overweight on insulin resistance in T1DM.