Rapid appearance and onset of action of insulin aspart in paediatric subjects with type 1 diabetes

The pharmacokinetics of the novel, rapid-acting insulin aspart were compared with those of soluble human insulin following subcutaneous administration in nine children (aged 6–12 years) and nine adolescents (aged 13–17 years) with stable type 1 diabetes. The study had a randomised, double-blind, two-period crossover design. Each patient received a single subcutaneous dose of insulin aspart or human insulin (0.15 IU/kg body weight) 5 min before breakfast and the plasma insulin and glucose concentrations were measured at intervals during the following 5 h. The pharmacokinetic profile of insulin aspart differed significantly from that of human insulin with a higher mean maximum serum insulin (C_{max ins}), 881 ± 321 (SD) pmol/l versus 422 ± 193 pmol/l for human insulin (P < 0.001); and with a shorter median serum insulin t _{max ins}, 40.0 min (interquartile range: 40–50 min) versus 75.0 min (interquartile range: 60–120 min) for human insulin, (P < 0.001). An age-related effect on C_{max ins} and area under the curve (AUC_{0–5h ins}) was observed with higher values in adolescents than in children for both insulin aspart and human insulin. Postprandial glycaemic control was improved with insulin aspart; the baseline-adjusted ΔC_{max glu} being lower for insulin aspart compared with human insulin (increase of 7.6 ± 5.1 versus 9.4 ± 4.4 mmol/l respectively, P < 0.05). The incidence of adverse events was similar for the two insulin types. Conclusion The more rapid onset of action of insulin aspart versus human insulin, previously observed in adults, is confirmed in a paediatric population with type 1 diabetes. Received: 30 June 1999 and in revised form: 20 September 1999 and 23 November 1999 /Accepted: 9 December 1999     

初发1型糖尿病患儿酮症酸中毒的调查

目的调查初发1型糖尿病患儿酮症酸中毒(DKA)的发生情况。方法以224例初发1型糖尿病患儿为研究对象,进行回顾性分析,分为DKA组和未合并DKA组,各112例。DKA组患儿根据年龄分为≥5岁组(65例)和5岁组(47例),并根据酸中毒情况分为轻度(26例)、中度(29例)、重度(57例)3组。分析DKA发生的影响因素以及不同年龄DKA患儿的临床及实验室特点。结果 224例初发1型糖尿病患儿中最常见的症状为多饮(86.2%)、多尿(78.6%)及体重下降(57.1%)。与未合并DKA患儿比较,DKA组5岁、低收入、父母教育程度高中及以下所占的比例均较高,随机血糖、Hb A1C水平较高,pH、HCO_3~-及C肽水平更低,差异均具有统计学意义(P0.05)。≥5岁组与5岁组的轻、中、重度DKA所占比例的差异无统计学意义(P0.05)。与5岁组相比,≥5岁组DKA患儿的症状持续时间较长,随机血糖较低,HbA1C、C肽水平较高,差异具有统计学意义(P0.05)。结论 1型糖尿病患儿DKA发生率高,DKA的发生与年龄、父母文化程度及家庭收入有关。     

初发1型糖尿病儿童辅助性Th1细胞因子紊乱相关因素分析

目的：检测初发1型糖尿病患儿IL-1β、IL-12、IL-18、TNF-α等细胞因子水平,并分析其与感染、起病时间等临床指标相关性。方法：选择初发1型糖尿病患儿33例为病例组,依据外周血白细胞（WBC）水平将33例患儿分为WBC增高组和WBC正常组;另选取健康体检儿童27例为对照组。应用酶联免疫吸附法检测血清IL-1β、IL-12、IL-18、TNF-α等细胞因子水平;同时检测病例组患儿血气pH值、血糖、血乳酸、果糖胺、外周血白细胞及中性粒细胞等各临床指标水平。结果：病例组细胞因子 IL-12水平高于对照组（P＜0.001）。病例组IL-18水平与发病时间呈负相关（r=-0.413,P=0.015）;中性粒细胞与IL-1β水平呈正相关（r=0.413,P=0.023）;外周血WBC与IL-18水平亦呈正相关（r=0.352,P=0.038）。WBC增高组细胞因子IL-1β、IL-12、IL-18水平高于WBC正常组(均P＜0.05)。结论：1型糖尿病患儿存在Th1细胞分泌细胞因子紊乱,感染可进一步提高细胞因子的分泌水平,可能推动了早期糖尿病起病过程。     

Psychological issues in the care of children and adolescents with type 1 diabetes

The present article highlights some of the psychological issues in children and adolescents with type 1 diabetes and provides health professionals with some strategies for addressing them.     

Continuous glucose monitoring system during physical exercise in adolescents with type 1 diabetes

Aim: Continuous glucose monitoring system (CGMS) provides detailed information on glucose fluctuations. The aim was to establish whether CGMS could be used during physical exercise and whether it detects more episodes of hypoglycaemia and hyperglycaemia than frequent blood glucose measurements. Methods: Adolescents with type 1 diabetes (12 girls and 47 boys) participated in three annual sports camps that lasted for 3–4 days and included different types of exercise: soccer, floorball + cross‐country skiing and golf. During the study, blood glucose values, mean 8.7 ± 3.3 per day, were obtained with Hemocue in parallel with the CGMS. Results: Ninety‐eight per cent of the participants used the sensor at all times during the camps. Eighty‐seven per cent of the sensors gave adequate signals for 24 h and 66% for 48 h. Median durations of hypoglycaemia and hyperglycaemia were 1.7 h per day and 3.8 h per day, respectively. The CGMS identified significantly more episodes of hypoglycaemia (p < 0.005) and hyperglycaemia (p < 0.005) during the day and night than frequent blood glucose tests. Conclusion: We demonstrate that, even during days that included episodic strenuous physical exercise, CGMS could provide useful information on glucose fluctuations during day and night, albeit with significant failure rates.     

Echocardiographic load-independent indices of contractility in children and adolescents with type I diabetes: Effect of metabolic control and insulin on left ventricular performance

A case-control study was carried out in a tertiary referral teaching hospital to evaluate left ventricular contractility in children and adolescents with type 1 diabetes and to study factors influencing left ventricular contractility. Thirty-four children and young adults with type 1 diabetes (age 10.8–21.8 years) were randomly selected from approximately 400 patients of the same age range in the outpatient department and compared with 16 nondiabetic controls (age 7.3–21.2 years). The relation of end-systolic wall stress to velocity of circumferential fiber shortening as a standard deviation score (SDS) from the normal range described by Colan et al. was used to assess left ventricular contractility. In the diabetic group the effect of age, duration of diabetes, metabolic control, insulin dose, and autonomic function on left ventricular contractility were studied. It was found that the end-systolic wall stress-velocity of circumferential fiber shortening relation was not different between diabetic subjects and controls [+0.52 (SEM 0.21) vs +0.90 (SEM 0.26) SDS,p=0.3]. In the diabetic subjects, the end-systolic wall stress-velocity of circumferential fiber shortening relation was positively correlated with glycated hemoglobin (r=0.37,p=0.03) and insulin dose per kilogram of body weight (r=0.36,p=0.04). Those two variables together explained 24% of the variability in the end-systolic wall stress-velocity of circumferential fiber shortening relation. Twenty-eight of the diabetic subjects were also assessed for cardiac autonomic function. Disturbances of cardiac autonomic function were not associated with increased contractility. It is concluded that left ventricular contractility assessed by load-independent echocardiographic indices was not different between children and adolescents with type 1 diabetes and controls. However, increased contractility was positively related to unfavorable metabolic control and higher insulin dose.     

Prepubertal girls with insulin-dependent diabetes mellitus have higher exogenous insulin requirement than boys

In a population based study, the prescribed insulin dose of 348 prepubertal children with insulin-dependent diabetes mellitus (IDDM) was analysed 2 years after the diagnosis of diabetes. Girls had an insulin dose 13.6% higher than that in boys. When children younger than 5 years of age at diagnosis were analysed separately, the difference in insulin dose between boys and girls remained. The increased insulin dose in girls was not explained by possible differences in endogenous insulin secretion, body mass index, metabolic control or the number of daily insulin injections. Our observations indicate that prepubertal girls with IDDM have a poorer insulin sensitivity than boys. Received: 26 May 1997 / Accepted in revised form: 26 January 1998     

Starting insulin therapy in children with newly diagnosed diabetes

Eight years ago, a decision was made to eliminate unnecessary hospitalization of children with newly diagnosed diabetes mellitus. This decision required changes in the basic approach to starting insulin therapy and education of the parents. Since then, 52 children aged 11 months to 16 years have been treated. Forty-four of these children were sent home after one to four hours of instruction. Five children received intravenous therapy for two to five hours and then went home. The remaining three children were admitted to the hospital for 18 to 40 hours. Subsequent establishment, at home, of diabetes control was accomplished without incident. The first injection of subcutaneous insulin was generally a combination of regular and slowly absorbed insulin. This approach has been well received by patients, parents, and referring physicians.     

儿童1型糖尿病胰岛素泵治疗长期随访的疗效观察

目的 比较1型糖尿病(T1DM)患儿应用持续皮下胰岛素输注(CSII)与每日多次皮下胰岛素注射(MDI)治疗对血糖控制的疗效差异.方法 回顾性收集91例应用CSII方式治疗1年以上T1DM患儿的临床资料,评估其糖化血红蛋白(HbA1C)水平、糖尿病酮症酸中毒(DKA)再发生情况,通过与75例应用MDI治疗的T1DM患儿...     

Telemedical support to improve glycemic control in adolescents with type 1 diabetes mellitus

Introduction In this paper, we evaluated the feasibility of a telemedical (TM) support program and its effect on glycemic control in adolescents with type 1 diabetes mellitus (T1DM). Thirty-six adolescents (m=20, median age at the start of the study: 15.3 years (range: 10.7–19.3 years), median age at diagnosis: 9.3 years (2.1–13.8 years), median duration of disease: 6.4 years (1.0–12.8 years), HbA1c>8%, all on intensified insulin therapy) were randomized in a crossover trial over 6 months (3 months with TM, 3 months with conventional support and paper diary (PD)). During the TM phase, the patients sent their data (date, time, blood glucose, carbohydrate intake, insulin dosage) via mobile phone, at least daily, to our server and diabetologists sent back their advice via short message service (SMS) once a week.Results Glycemic control improved during the TM phase, while it deteriorated during the PD phase: TM-PD group HbA1c (%, median (range)): 9.05 (8–11.3) (at 0 months), 8.9 (6.9–11.3) (at 3 months), and 9.2 (7.4–12.6) (at 6 months), and PD-TM group: 8.9 (8.3–11.6), 9.9 (8.1–11), and 8.85 (7.3–11.7) (p<0.05). Patients rated the TM support program to be a good idea. Technical problems with General Packet Radio Service (GPRS) data transmission led to data loss and decreased patient satisfaction.Conclusion Our telemedical support program, VIE-DIAB, proved to be feasible in adolescents and helped to improve glycemic control.     

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.     

Continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: Do the benefits outweigh the risks?

Intensive management of diabetes is the gold standard in the treatment of children with type 1 diabetes. Novel insulin delivery techniques have been developed to improve the ability to administer multiple daily doses of insulin. Continuous subcutaneous insulin infusion (CSII) is a method of insulin delivery that is increasing in popularity. The present article reviews the risks and benefits of CSII in children. At this time, there is limited quality published evidence to make a definitive claim about the potential risks and benefits of CSII in children. The risk of diabetic ketoacidosis and individual family factors must be considered before initiation of treatment.     

肠道微生物与1型糖尿病

研究显示肠道微生物在免疫相关性疾病的发病中起到重要的作用.1型糖尿病作为一种自身免疫性疾病,其发病机制与肠道微生物的关系的研究也逐渐增多.肠道微生物的改变是1型糖尿病发病的重要危险因素,这在动物模型研究中已经得到证实.该文就肠道微生物对1型糖尿病的作用进行综述,并探讨微生物对宿主免疫反应的影响以及1型糖尿病未来可能的预防及治疗方案.     

Mixing rapid-acting insulin analogues with insulin glargine in children with type 1 diabetes mellitus

OBJECTIVE: To determine whether mixing insulin glargine (IG) with a rapid-acting insulin (RAI) analogue in the same syringe had any deleterious effects on glycemic control in children with type 1 diabetes mellitus. STUDY DESIGN: Data from 55 children mixing the IG with a RAI analogue was collected for 6 months before and 6 months after the insulin mixing began. Data from a control group of 55 children not mixing the insulins was collected at similar intervals. Parameters evaluated included hemoglobin A1c (HbA1c) values, number of non-severe and severe hypoglycemic events, number of diabetic ketoacidosis (DKA) events, and blood glucose distribution patterns. RESULTS: After 6 months of study, HbA1c values were equivalent for the control and test groups (8.54+/-1.14 vs 8.61+/-1.14, respectively; P=1.0000). Percentages of blood glucose values in, above, and below the target range did not vary significantly in the groups. There were no significant differences in the groups in the occurrence of non-severe or severe hypoglycemic events or of DKA events. CONCLUSION: There were no significant differences in glycemic control between children who mixed IG in the same syringe with a RAI analogue compared with children who took separate injections.     

Low levels of vitamin D in North Indian children with newly diagnosed type 1 diabetes

Borkar VV, Devidayal, Verma S, Bhalla AK. Low levels of vitamin D in North Indian children with newly diagnosed type 1 diabetes. Background: To find out whether vitamin D levels are lower in children with newly diagnosed type 1 diabetes (T1D) as compared to non‐diabetic subjects. Methods: Plasma levels of vitamin D (25‐OHD) were measured by high performance liquid chromatography (HPLC) in 50 children aged between 6 and 12 yr within a week of diagnosis of T1D, and in 50 healthy children. Results: The mean levels of vitamin D were significantly lower in patients as compared to their controls [20.02 ± 10.63 ng/mL (50.05 ± 26.57 mmol/L) vs. 26.16 ± 12.28 ng/mL (65.4 ± 30.7 mmol/L), p‐value 0.009]. Twenty‐nine (58%) children in the study group were vitamin D deficient (25‐OHD level < 20 ng/mL or < 50 mmol/L) as compared to only 16 (32%) in the control group. Overall, 43 (86%) diabetic and 38 (76%) healthy children were either vitamin D deficient or insufficient. Conclusion: These results suggest that vitamin D levels are low at the onset of T1D, and they strongly support the need for further clinical studies to prospectively evaluate the effect of vitamin D supplementation on T1D rates in this patient population.     

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目的应用动态血糖监测系统(CGMS)观察1型糖尿病患儿血糖控制情况,寻找评价和改善血糖控制的方法。方法收集复旦大学附属儿科医院2003年10月至2004年6月内分泌科门诊随访的儿童1型糖尿病患者28例,男16例,女12例,年龄(13.1±4.5)岁,病程(5.5±3.4)年,其中21例采用每天多次胰岛素注射(MDI),另7例使用胰岛素泵连续胰岛素输注(CSII)治疗。动态监测血糖3d,同时指尖血糖监测≥4次/d。结果(1)研究对象体重指数(BMI)为(19.4±3.0)kg/m2,糖化血红蛋白(HbA1c)为(8.4±1.6)%。CSII组HbA1c(8.2±1.0)%,MDI组HbA1c(8.5±1.8)%,差异有显著性意义(P<0.05);(2)CGMS发现22例77次餐后2h高血糖,CSII组4例(57.1%),每例出现1次,MDI组18例(85.7%),每例出现(4.1±2.5)次,差异显著(P<0.01);(3)CGMS发现17例79次低血糖,持续时间(76.6±92.8)min,而指尖血糖监测仅发现19次低血糖;白天低血糖持续时间(41.5±39.1)min,夜间(112.4±117.1)min,夜间低血糖持续时间显著长于白天(P<0.01)。(4)HbA1c≤8%组餐后高血糖发生率低于HbA1c>8%组(P<0.05),而低血糖的发生率显著升高(P<0.01)。结论1型糖尿病患儿多数存在低血糖和餐后高血糖;动态血糖监测系统是发现血糖异常波动的有效工具。动态血糖监测对指导1型糖尿病治疗,调整胰岛素剂量,从而改善血糖控制有着重要的临床意义。     

Self-concept, attitude toward illness and family functioning in adolescents with type 1 diabetes

OBJECTIVES:

The primary objective of the present study was to assess self-concept in adolescents with type 1 diabetes, and to determine whether this is associated with attitudes toward having chronic disease, family functioning or severity of diabetes. The secondary objective was to assess the impact of family income, sex, age and age at diagnosis on adolescent self-concept.

METHODS:

A cross-sectional, self-report survey of 48 adolescents with type 1 diabetes (22 boys and 26 girls; mean ± SD age at time of study 15.2±1.7 years [range 12.2 to 18.0 years]; mean age at diagnosis 9.2±3.3 years [range 1.3 to 14.9 years]) was performed using the Piers-Harris Children’s Self-Concept (PHCSC) scale, second edition; the Child Attitude Toward Illness Scale; and the Family Assessment Measure scale, version III. Demographic information including net family income and a symptom inventory form to assess disease severity was collected.

RESULTS:

Adolescents’ self-concept measured by the PHCSC scale was significantly positively correlated with a more positive attitude toward chronic illness as measured by the Child Attitude Toward Illness Scale. The PHCSC scale was found to have a significant negative correlation with the Family Assessment Measure scale score, indicating that a better self-concept was correlated with enhanced family functioning. Self-concept was not significantly correlated with disease severity, income of family, sex, age at diagnosis, age at time of study, episodes of diabetic ketoacidosis or episodes of hypoglycemia.

CONCLUSIONS:

Adolescents with better self-concept had more positive attitudes toward their chronic illness and enhanced family functioning. Although no correlation with diabetes disease severity was seen in the study population, interventions aimed at improving adolescent self-concept may have a positive impact on diabetes treatment by improving attitude toward living with type 1 diabetes.     

Rate of hypoglycaemia and insulin dosage in children during the initial therapy of type 1 diabetes mellitus

Hypoglycaemia is a major side-effect of insulin treatment. It is known that young children with type 1 diabetes mellitus (T1DM) show a higher risk of hypoglycaemia than older children. This study was performed to analyse the incidence of hypoglycaemia within the first 14 days (day 1–day 14) of insulin treatment in children at the onset of T1DM and to evaluate the influence of age and insulin dosage. The Paediatric Quality Initiative (DPV), including data from 121 centres in Germany and Austria, provided anonymous data of 1,680 patients (age 0.7–18.8 years; 799 girls) at the onset of T1DM. Hypoglycaemia was defined as a blood glucose level (BG) <2.8 mmol/l (50 mg/dl). The hypoglycaemia rate rose continuously from day 2 (4.8%) to day 5 (11.2%) and then remained stable between 8.7%–11.2% until day 14. The hypoglycaemia rate was higher in younger than in older children ( P <0.0001). Multiple regression analysis revealed an influence of age ( P <0.0001), insulin dosage ( P =0.0034), and route of initial treatment ( P =0.0052) on the hypoglycaemia rate. From day 2 to day 14, the insulin dosage itself was higher in females than in males ( P =0.0147), in patients with high HbA1c ( P =0.0001), high BG ( P <0.0001), or low pH ( P <0.0001). There was no influence of age on the insulin dosage. Conclusion: During the first 14 days after onset of type 1 diabetes mellitus, young children, intravenous-treated patients and patients receiving a high insulin dosage are at particular risk of developing hypoglycaemia. In order to avoid hypoglycaemia, blood glucose should be measured frequently and the insulin dosage should be carefully adjusted. Low blood glucose levels should be treated promptly.