Difficulties or mistakes in diagnosing type 1 diabetes in children?—demographic factors influencing delayed diagnosis

Background: Diabetic ketoacidosis (DKA) development in children with new‐onset type 1 diabetes (T1DM) is often the main consequence of delayed diagnosis. The aim of the study was to estimate the frequency of difficulties in T1DM diagnosis and to investigate if and how the demographic factors (gender, patient's age at presentation, family history of T1DM, level of maternal education, place of residence, and health service unit the patient called at) have any influence on diagnostic delays. Subjects and methods: Retrospective analysis of 474 children (243 boys—51.27% and 231 girls ?48.73%) with new‐onset T1DM aged below 17 yr and living in the Pomeranian region of Poland was carried out. The delay in diagnosis was recognized if the patient was not diagnosed on the first visit because of omission, wrong interpretation of main diabetic symptoms, exclusive treatment of additional signs, or concomitant diseases. Results: Difficulties in diagnosing T1DM were found in 67 cases (14.13%) and they are the main cause of DKA development in these children (p = 0.00). Among the examined demographic factors, mainly the patient's age at presentation has a significant influence on diagnostic delays (p = 0.01), especially in children below 2 yr (p = 0.00). Most frequently family doctors were responsible for wrong preliminary diagnosis. Conclusions: Difficulties in diagnosing T1DM are a significant cause of DKA development in children with new‐onset disease. Patient's age at presentation is the main risk factor of delayed diagnosis, especially in children below 2 yr. The increase in awareness among pediatricians concerning the possibility of T1DM development in children is needed.     

儿童糖尿病198例

目的 探讨儿童糖尿病(DM)的临床特点,为临床诊治提供理论依据.方法 对1999年1月-2009年3月在本院住院的198例DM患儿的临床表现和实验室检查进行回顾性临床分析.结果 198例DM患儿中,男97例,女101例.均为首诊病例;发病高峰年龄为5～6岁及9～11岁;首诊例数逐年增加,2008年较1999年增加了3.7倍;其中1型糖尿病(T1DM) 174例(占88.9％),2型糖尿病7例(占3.5％),新生儿DM 14例(占7.1％),其他3例(占1.5％).首诊的TlDM患者中,酮症酸中毒(DKA)的发生率为42.0％;发病前有感染史者55例,与无感染史者比较,DKA的发生率有统计学差异(P＜0.01).有DM家族遗传史者23例.并甲状腺功能亢进症2例;并暂时性甲状腺功能减低症31例;并肝功能异常30例,肾功能异常12例,血脂异常48例,尿蛋白阳性27例.糖化血红蛋白为(12.0±1.8)％;共分析了25例T1 DM患者的自身抗体,胰岛细胞抗体阳性率为28％,胰岛素自身抗体的阳性率为20％,谷氮酸脱羧酶自身抗体(GADA)阳性率为72％.结论 首诊的儿童DM逐年增加,以T1DM为主;新生儿DM增加明显;DKA是T1DM患者就诊的重要原因;首诊的T1DM者中,感染是发生DKA的重要诱因;儿童DM常合并暂时性甲状腺功能减低症、肝肾功能异常及血脂异常;糖尿病自身抗体中GADA的阳性率最高.     

Predicting diabetic ketoacidosis in children by measuring end-tidal CO2 via non-invasive nasal capnography

AIM: To determine if nasal capnography can be used as a screening tool to predict diabetic ketoacidosis (DKA) in children with Type 1 diabetes mellitus (T1DM) presenting to the emergency department. METHODS: Cross-sectional, prospective, observational study of children with T1DM who presented to the Emergency Department of Princess Margaret Hospital for Children, Western Australia, over a 12-month period from June 2003 to June 2004. Information on demographic data and T1DM was recorded. Nasal capnography, venous blood gases and urinary analysis were performed on patients. Data were analysed using chi(2) tests and receiver operating characteristic curve analysis. Sensitivities and specificities were calculated at different end-tidal carbon dioxide (ETCO(2)) levels to predict presence of DKA. RESULTS: Fifty-eight patients aged 1-18 years (mean 10.7, SD 4.7) were analysed. Thirty-three (57%) were male and 30 (52%) presented with new onset of T1DM. Of the 58 cases, 15 (26%) had DKA, and 11 of these were new T1DM patients. No patients with an ETCO(2) > 30 mmHg had DKA (sensitivity 1.0, specificity 0.86). Six patients with an ETCO(2) < 30 mmHg did not have DKA. CONCLUSIONS: Nasal capnography in conjunction with clinical assessment is predictive of DKA. Further research into this area with larger numbers could help validate ETCO(2) as a screening tool for DKA in the emergency department.     

5岁以下1型糖尿病患儿21例

目的探讨5岁以下婴幼儿糖尿病的临床特点、诊断及酮症酸中毒(DKA)的抢救措施。方法回顾性分析21例5岁以下婴幼儿糖尿病患儿的发病情况、临床特点、误诊情况,并探讨急救治疗体会。结果婴幼儿糖尿病临床症状不典型,糖尿病自身抗体阳性率低,初诊误诊率达52.4%,DKA发生率也高达52.4%。感染是诱发DKA的常见原因,患儿无1例死亡,1例放弃治疗,出院后治疗依从性不一。结论婴幼儿糖尿病多为特发性,临床症状不典型,易误诊、漏诊。感染可能导致患儿糖尿病的进展和临床表现出现。小剂量胰岛素持续静滴、调节酸碱平衡和纠正电解质紊乱是急救的关键。     

Increased incidence and severity of diabetic ketoacidosis among uninsured children with newly diagnosed type 1 diabetes mellitus

OBJECTIVES: (a) To determine the incidence and severity of diabetic ketoacidosis (DKA) and (b) to stratify according to insurance status at the initial diagnosis of type 1 diabetes (T1DM). RESEARCH DESIGN AND METHODS: Subjects included children <18 yr who presented with new-onset T1DM from January 2002 to December 2003 and were subsequently followed at the Barbara Davis Center. Insurance status and initial venous pH were obtained. RESULTS: Overall, 383 subjects presented with new-onset T1DM and 359 (93.7%) were enrolled. Forty-three (12.0%) of these children were uninsured and 40 (11.1%) had Medicaid. One hundred and two (28.4%) subjects presented with DKA. When compared to the insured subjects, uninsured subjects had a significantly increased risk of presenting with DKA [odds ratios (OR): 6.19, 95% CI 3.04-12.60, p < 0.0001], as well as presenting with severe DKA, defined as venous pH <7.10 (OR: 6.09, 95% CI 3.21-11.56, p < 0.0001). There were no differences, however, between the insured and Medicaid subjects in their probability of presenting with DKA or severe DKA. The risk of presenting with DKA (as well as with severe DKA) was the highest among patients <4 yr old. CONCLUSIONS: At the time of initial diagnosis, uninsured patients were more likely to present with DKA than insured patients. Furthermore, when the uninsured subjects presented with DKA, the condition tended to be more severe and life-threatening. A potential explanation is that uninsured subjects may delay seeking timely medical care, thereby presenting more critically ill, whereas insured subjects may have their T1DM diagnosed earlier.     

25-羟维生素D与儿童1型糖尿病及酮症酸中毒的相关性研究

目的探讨血清25-羟维生素D[25-(OH)D]水平与儿童1型糖尿病(T1DM)及酮症酸中毒(DKA)的相关性。方法选取2006年1月—2009年12月期间152例住院患儿,其中52例为首次发病的T1DM患儿,包括酮症酸中毒(DKA组)21例,以及非酮症酸中毒(非DKA组)31例,其余100例为非T1DM组。检测并比较三组患儿的血清25-(OH)D水平,分析血清25-(OH)D水平与儿童T1DM及DKA的相关性。结果 DKA组患儿的血清25-(OH)D平均为(53.6±27.8)nmol/L,显著低于非DKA组的(69.7±27.9)nmol/L和非T1DM组的(81.8±28.3)nmol/L(P<0.05);非DKA组患儿的血清25-(OH)D水平显著低于非T1DM组(P<0.05)。结论 T1DM患儿的血清25-(OH)D水平低,尤以DKA患儿最为明显,维生素D在儿童T1DM发病中的潜在保护效应值得关注。     

浙江省1999～2004年新诊断儿童1型糖尿病流行病学特征及血脂水平

目的 探讨浙江省新诊断儿童1型糖尿病（DM）患儿流行病学特征及血脂特点。方法对1999年1月1日～2004年12月31日住院且为首次发病的101例1型DM患儿的年龄发病时间、出生时间、酮症酸中毒（DKA）及血脂特点进行回顾性分析。结果2004年新诊断的1型DM病人与总住院人数之比高于1999年；男童中12岁以上组病例所占同性别比例高于同年龄组女童（27．5％vs4．9％）.新诊断1型DM患儿出生于10月份至次年1月份者多于2～5月份出生者，同期发病的病例与总住院人数之比也明显升高。新诊断病例DKA组血糖和糖化血红蛋白（HbAlc）较非DKA组明显升高。两组总胆固醇（TC）和三酰甘油（TG）有显著性差异。血脂异常组与血脂正常组并DKA的比率有显著性差异，两组血糖、HbAlc和住院时间差异有显著性。结论儿童1型DM与总住院人数之比早逐年上升趋势；其发病可能与青春发育有关。初发1型DM患儿的DKA发生率又有回升。1型DM患儿TC、TG与血糖和HbAlc水平相关。     

Delayed diagnosis in type 1 diabetes mellitus

Children with suspected type 1 diabetes mellitus (T1DM) should have same day referral to a paediatric diabetes team. 99 children (54 male; median age 10.5 years, range 0.9-15.9 years) were diagnosed with T1DM at our hospital between January 2004 and June 2007. 27 (27.2%) presented in diabetic ketoacidosis (DKA). 37 (37.3%) required hospital admission, while the rest had ambulatory management. In 21 (21.2%) children, diagnosis was delayed >24 h (median 3.0 days, range 1-14 days) due to missed diagnosis at the local hospital (four) or by the general practitioner (seven), arranging a fasting blood glucose test (nine) and outpatient appointment requested via fax (one). Children with delayed diagnosis presented more frequently in DKA (52.3% vs 20.5%, p<0.01), with a higher median presenting HbA1c (12.3% vs 10.9%, p<0.05). There were no differences in age and sex between the delayed diagnosis and immediate referral groups. Healthcare providers need to be aware of the importance of immediate referral of children newly diagnosed with T1DM.     

Ketoacidosis at presentation of type 1 diabetes in children in Kuwait: frequency and clinical characteristics

Abdul‐Rasoul M, Al‐Mahdi M, Al‐Qattan H, Al‐Tarkait N, Alkhouly M, Al‐Safi R, Al‐Shawaf F, Mahmoud H. Ketoacidosis at presentation of type 1 diabetes in children in Kuwait: frequency and clinical characteristics. Background: Diabetic ketoacidosis (DKA) has significant morbidity and mortality, and is common at diagnosis in children. Objective: Describe the frequency and severity of DKA at diagnosis of type 1 diabetes mellitus (T1DM) in children in Kuwait. Methods: Hospital records of 677 diabetic children less than 12 yr of age, diagnosed during the period of 2000–2006 were reviewed. DKA was defined as blood glucose > 11 mmol/L, pH < 7.3, and/or bicarbonate < 15 mmol/L with ketonuria. Results: Of all patients diagnosed with T1DM, 255 (37.7%) presented with DKA. The frequency of DKA was constant between 2000 and 2002 (42.7–41.5%), but decreased in the following years to 30.7% in 2006 (p < 0.005). The majority had either mild or moderate DKA (74.1%). Fifty‐one (36.7%) of all children in the 0–4 yr had severe DKA compared to ten (2.9%) in the 5‐ to 8‐yr‐old group, and three (1.5%) in 9‐ to 12‐yr‐old patients (p < 0.0001). Moreover, 83% of children with severe DKA were in the 0–4 yr age group. One child (0.15%) died and twenty‐seven (4%) needed intensive care unit (ICU) care. Conclusion: Our study provides recent data on Middle Eastern population, for whom data are sparse. Although it has significantly decreased, the frequency of DKA at presentation of T1DM in children in Kuwait is still high, secondary to the high prevalence of diabetes in the community. Young children, especially those less than 2 yr old remain at high risk. Increasing the general awareness of the public as well as of pediatricians to the disease may lead to early diagnosis before the development of acidosis.     

交感神经皮肤反应在糖尿病患儿周围神经病早期诊断中的应用

目的探讨交感神经皮肤反应(SSR)在儿童糖尿病周围神经病交感神经纤维病变早期诊断的应用价值。方法对35例1型糖尿病(T1DM)儿童和30例健康儿童四肢分别进行电刺激SSR检测,测量每个肢体的平均起始潜伏期和峰-峰波幅,并比较2组各肢体的SSR起始潜伏期及峰-峰波幅差异。同时对T1DM组儿童进行神经传导速度(NCV)的检测,并对NCV检测异常率与SSR检测异常率进行比较。另外,还对有酮症酸中毒(DKA)史和无DKA史的2组患儿SSR检测异常结果进行比较。结果 T1DM组患儿各肢体SSR起始潜伏期均较健康对照组明显延长(Pa<0.05)。健康对照组30例四肢均可引出SSR波形,T1DM组31例患儿四肢均可引出SSR波形;4例患儿至少有一肢不能引出SSR波形(11.4%),其中2例患儿四肢均未引出SSR波形(5.7%);21例(60%)患儿至少有一肢SSR缺失或起始潜伏期异常,其中15例(71.4%)有DKA史,高于无DKA患儿异常检出率(6例,42.9%),但2组比较无统计学差异。T1DM组患儿NCV检测异常10例(28.6%),较SSR起始潜伏期的检出异常率低,两者比较差异无统计学意义(P>0.05)。结论 SSR检测可早期发现糖尿病周围神经病交感神经小纤维病变,较NCV敏感。     

儿童 1型糖尿病 30年临床特征及随访观察

目的 分析儿童1型糖尿病（T1DM）的临床特征,探讨该病对儿童生长发育的影响程度及后期并发症发生的情况。方法 对发病年龄在13个月至14．7岁,经实验室检查确诊为T1DM的210例患儿的临床特征进行了回顾性分性,并对99例患儿进行了1～24年的并发症、生长发育、死因随访。结果 因单纯糖尿病人院者47例（22．4％）;伴酮血症入院者69例（32．9％）;伴酮症酸中毒入院者94例（44．7％）,其中农村患儿78例。起病时有诱因者43例,其中自停胰岛素15例。酮症酸中毒患儿住院时间明显比单纯糖尿病患儿长（P〈0．05）。随访的99例中出现各种并发症50例,其中以微血管病变发生率最高。病程长易并发各种并发症（P〈0．05）,病后的监测方法与并发症的发生也明显相关。患儿组身高明显低于对照组（P〈0．05）。结论 酮症酸中毒是儿童糖尿病的基本特征;病程长易并发各种并发症;加强对儿童糖尿病患者的血糖检测和病后教育,将对儿童糖尿病的治疗起重要作用。     

Diabetic Ketoasidosis is Associated with Prothrombotic Tendency in Children

Children and adolescents with type I diabetes mellitus (DM) may present with diabetic ketoacidosis (DKA), which is associated with significant morbidity and mortality. This study aimed to evaluate the hematological parameters at diagnosis (0th hour) and 96th hour after the initiation of treatment in children with DKA. Twenty-six children with DKA treated in Dicle University Faculty of Medicine between September 2002 and August 2003 were included in this study. General characteristics of the patients and hematological parameters (platelet count, white blood cell count, prothrombin time, partial thromboplastin time (PTT), bleeding time, coagulation time, protein C, protein S, antithrombin III, fibrinogen, D-dimer, factor VIII, factor IX, and factor X levels) at diagnosis (0th hour) and 96th hour after the initiation of treatment were determined. The mean age of the children (10 girls and 16 boys) was 9.15 ± 3.85 years (range: 4–15 years). DKA developed for the first time in 58.3% of these children and they had recently been diagnosed as DM. After hematological parameters at 0th hour were evaluated, increased platelet count, decreased PTT, low protein C, and high factor VIII levels were determined at diagnosis, indicating prothrombotic tendency. If the hematological parameters at 0th hour were compared with those at 96th hour; platelet count decreased, PTT increased, protein C and factor VIII levels turned to be normal at 96th hour. When all the results are considered together, children with DKA appeared to have a prothrombotic tendency. Although this tendency was not reflected in clinical findings in this study, it should be kept in mind that children with DKA are prone to the development of thrombosis and they need to be investigated for the possibility of thrombosis.     

Diabetic ketoasidosis is associated with prothrombotic tendency in children

Children and adolescents with type I diabetes mellitus (DM) may present with diabetic ketoacidosis (DKA), which is associated with significant morbidity and mortality. This study aimed to evaluate the hematological parameters at diagnosis (0th hour) and 96th hour after the initiation of treatment in children with DKA. Twenty-six children with DKA treated in Dicle University Faculty of Medicine between September 2002 and August 2003 were included in this study. General characteristics of the patients and hematological parameters (platelet count, white blood cell count, prothrombin time, partial thromboplastin time (PTT), bleeding time, coagulation time, protein C, protein S, antithrombin III, fibrinogen, D-dimer, factor VIII, factor IX, and factor X levels) at diagnosis (0th hour) and 96th hour after the initiation of treatment were determined. The mean age of the children (10 girls and 16 boys) was 9.15 ± 3.85 years (range: 4-15 years). DKA developed for the first time in 58.3% of these children and they had recently been diagnosed as DM. After hematological parameters at 0th hour were evaluated, increased platelet count, decreased PTT, low protein C, and high factor VIII levels were determined at diagnosis, indicating prothrombotic tendency. If the hematological parameters at 0th hour were compared with those at 96th hour; platelet count decreased, PTT increased, protein C and factor VIII levels turned to be normal at 96th hour. When all the results are considered together, children with DKA appeared to have a prothrombotic tendency. Although this tendency was not reflected in clinical findings in this study, it should be kept in mind that children with DKA are prone to the development of thrombosis and they need to be investigated for the possibility of thrombosis.     

Ketoacidosis at presentation of type 1 diabetes mellitus in children: a retrospective 20-year experience from a tertiary care hospital in Serbia

Diabetic ketoacidosis (DKA) has significant morbidity and mortality and is common at diagnosis in children. The aim of this study was to determine the frequency and clinical characteristics of DKA over a 20-year period among children diagnosed with type 1 diabetes mellitus (T1DM) at University children's hospital in Belgrade, Serbia. The study population comprised of 720 patients (366 boys) diagnosed with type 1 diabetes aged <18 years between January 1992 and December 2011. Of all patients diagnosed with T1DM, 237 (32.9 %) presented with DKA. The majority had either mild (69.6 %) or moderate (22.8 %) DKA. Sixty (55.0 %) of all children under 5 years had DKA compared to sixty-two (20.9 %) in the 5- to 10-year-old group and one hundred fifteen (36.6 %) in the 11- to 18-year-old patients (p?<?0.01), while 2.5 % of the entire DKA cohort were in real coma. During the later 10-year period, children less often had DKA at diagnosis compared with the earlier 10-year period (28.0 vs. 37.4 %) (p?<?0.01), but the frequency of severe DKA was higher in the age group <5 year and in the age group >11 year during 2002–2011, compared with the earlier 10-year period (12.9 vs. 3.4 %, p?<?0.01 and 17.1 vs. 3.8 %, p?<?0.01). Conclusion: The overall frequency of DKA in children with newly diagnosed type 1 diabetes decreased over a 20-year period at our hospital. However, children aged <5 years and adolescents are still at high risk for DKA at diagnosis.     

Acute cerebral infarction and extra pontine myelinolysis in children with new onset type 1 diabetes mellitus

Neurological complications of diabetic ketoacidosis (DKA) are still associated with significant mortality and morbidity. We report on two children who suffered from acute cerebral infarction (CI) and extra pontine myelinolysis (EPM) at onset of type 1 diabetes. Initially, clinical management had not been performed according to generally accepted guidelines. Putative risk factors that may have predisposed for the development of acute cerebrovascular complications are discussed. Not only cerebral edema (CE) but also other severe neurological complications such as CI should be suspected when neurological deterioration occurs during DKA. We conclude that not only an exceeded rehydration therapy but also a rapidly reduced serum osmolality due to an unbalanced rapid blood sugar decrease and serum sodium increase may have lead to the neurological disease. We propose that a reserved and well-defined rehydration strategy in the first 6 (-12) h of therapy is crucial for recovery and can reduce neurological complications of patients with DKA.     

Clinical characteristics at presentation of type 1 diabetes mellitus in children younger than 15 years in Croatia

The aim of the study was to determine the clinical and biochemical characteristics of type 1 diabetes mellitus (DM) at presentation in children younger than 15 years in Croatia during a 9-year period, with special attention to diabetic ketoacidosis (DKA) incidence. The registered data set comprised blood glucose, pH, serum bicarbonate levels, and clinical symptoms at disease manifestation. During the study period, 692 children were diagnosed with type 1 DM. Polydipsia (96.7%), polyuria (96.05%), and weight loss (82.7%) were the most frequent symptoms anticipating disease detection. Enuresis was recorded in 11.55%. A total of 36.41% patients had DKA (pH < 7.3) at disease onset. During the 9-year period, the percentage of children presenting with DKA at time of diagnosis decreased from 41.67% to 33.33% (z = 1.68, p = 0.046). A positive family history of DM, the only factor with an impact on the DKA incidence rate in our population, lowers the probability of the development of ketoacidosis. This study confirms the importance of the detection of the classic symptoms of polyuria, polydipsia, and weight loss in patients with new-onset type 1 DM. The percentage of patients with DKA at diabetes onset decreased during the observed period but is still high and includes one-third of all patients. This is why in every acutely ill child, especially at a younger age, one should evaluate the possibility of type 1 DM to avoid the development of ketoacidosis.     

Young children (<5 yr) and adolescents (>12 yr) with type 1 diabetes mellitus have low rate of partial remission: diabetic ketoacidosis is an important risk factor

Objective:  To determine whether there are different rates of partial remission in preschool, school-age children, and adolescents with type 1 diabetes mellitus (T1DM) and to identify clinical characteristics that are associated with increased rate of partial remission.
Design/methods:  A total of 152 consecutive patients with newly diagnosed T1DM in 2004 were studied. Clinical characteristics at diagnosis, hemoglobin A1C (HbA1C), and total daily insulin dose (TDD) at 3-month interval follow-up for 1 yr were analyzed in each age-group (group 1, aged <5 yr; group 2, aged 5–12 yr; and group 3, aged >12 yr). Partial remission was defined as TDD <0.5 units/kg/d with HbA1C <8% assessed at 6 months after diagnosis.
Results:  Young children (group 1, 26.8%) and adolescents (group 3, 29%) had low rates of partial remission compared with school-age children (group 2, 56%, p = 0.002). There were no differences in the rates of diabetic ketoacidosis (DKA), autoantibody frequency, and HbA1C at diagnosis between age-groups. DKA at diagnosis was associated with less likelihood of having partial remission (p < 0.001). There were no associations between gender, autoantibodies, and HbA1C at diagnosis and the rate of partial remission.
Conclusions:  Young children and adolescent children with T1DM had a low rate of partial remission. Metabolic control was poorest in young children, whereas higher dose insulin in adolescents because of insulin resistance contributes to less likelihood of having partial remission. DKA at diagnosis was associated with low rate of partial remission. It is possible that the low frequency of honeymoon phase in young children reflects more aggressive beta-cell destruction in young children.     

已确诊的1型糖尿病患儿病程中酮症酸中毒发生情况及诱因调查

目的 调查已确诊的1型糖尿病（T1DM）患儿病程中糖尿病酮症酸中毒（DKA）的发生情况。方法 以首都医科大学附属北京儿童医院、上海交通大学附属儿童医院、南京医科大学附属南京儿童医院、郑州市儿童医院、江西省儿童医院、西安交通大学第一附属医院、昆明医科大学第一附属医院、武汉市妇女儿童医疗保健中心、苏州大学附属儿童医院、聊城儿童医院、福建省福州儿童医院、成都市妇女儿童中心医院12家医院登记系统为基础调查多中心1995年12月至2014年6月胰岛素治疗下的已确诊T1DM患者病程中发生DKA的频度和诱发原因。其中,T1DM确诊后发生的第1次DKA为组1A,第2次DKA为组1B。选择北京儿童医院2011年12月-至2012年5月T1DM患者血糖控制状况横断面调查病程中无DKA发生者为对照组,即组2。结果 12家医院共新诊断了1676例T1DM患儿,其中89例患者在病程中发生了100次DKA,发生比率为5.3%（89/1676）,发生频率为5.9%（100/1676）。且各中心的DKA发生比率不同,波动在1.1%～24.1%之间。组1A的糖化血红蛋白（HbA1c）［（11.31±3.03）% vs.（8.26±1.53）%,P＜0.01］及胰岛素剂量［（0.85±0.42）IU vs.（ 0.71±0.31）IU,P＜0.01］明显高于组2。组1A的胰岛素泵使用率高于组2（25.0% vs. 11.2%,P＝0.01）。而且,前者的自我血糖监测达标率（12.1% vs. 40.1%, P＜0.01）及复诊次数达标率（21.2% vs. 46.6%,P＜0.01）明显低于后者。组1A的DKA诱因主要是感染（33.7%）、中断胰岛素注射（21.3%）、饮食异常（20.2%）,1例患者为胰岛干细胞移植后DKA。组1B仍以感染为主要诱因（4/10）,1例患者因为胰岛素泵故障而发生DKA（1/10）。不同病程内发生的DKA诱因分布不同（P＜0.01）,1年内主要以中断胰岛素注射为主,占39.3%（11/28）;1年以上中断胰岛素注射仅占13.1%（8/61）,主要以感染（22/61）和饮食异常（16/61）为诱因。DKA发生率高的医院主要是以感染为诱因,达50%（12/24）,而DKA发生率低的医院感染诱因占28.1%（18/64）（P＜0.01）。结论 已确诊T1DM患者病程中DKA发生率为5.3%,各中心不同,最高达24.1%。DKA者的血糖控制水平差,不能规律的进行自我血糖监测及门诊复诊,应该强化糖尿病教育。胰岛素泵使用者及胰岛干细胞移植的患者成为新的教育关注点。DKA发生率高的医院需要强化患者学习感染时的处理措施。     

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??Abstract?? Objective To investigate the occurrance of DKA in established T1DM children. Methods According to the registration system in the following-hospitals??Beijing Children’s Hospital of Capital Medical University?? Children’s Hospital of Shanghai?? Nanjing Children’s Hospital??Children’s Hospital of Zhengzhou?? Children’s Hospital of Jiangxi?? the First Affiliated Hospital of Xi’an Jiaotong University??First Affiliated Hospital of Kunming Medical University?? Children’s Hospital of Wuhan?? SooChow University Affiliated Children’s Hospital?? Children’s Hospital of Liaocheng?? Children’s Hospital of Fuzhou?? Chengdu Women & Children’s Central Hospital???? we investigated the frequency and cause of DKA in children with established T1DM from December 1995 to June 2014. After the diagnosis of T1DM?? the first time DKA was for group 1A?? the second DKA for group 1B. We conducted a cross-sectional survey of blood glucose control status for patients with T1DM from December 2011 to May 2012 in Beijing Children’s Hospital. Patients who did not have DKA episode in the course of T1DM were selected as control group ??group 2??. Results Totally 1676 children were newly diagnosed with T1DM by 12 hospitals?? and 89 patients occurred 100 DKA after T1DM diagnosed. The incidence and frequency of DKA was 5.3% ??89/1676?? and 5.9% ??100/1676??. The frequency was different in 12 hospitals?? fluctuating between 1.1% and 24.1%. Compared with group 2?? group 1A had high level of HbA1c ???11.31±3.03??% vs. ??8.26±1.53??%?? P??0.01?? and insulin dosage ???0.85±0.42?? IU vs. ??0.71±0.31?? IU?? P??0.01??. There were more patients with insulin bump in group 1A than group2 ??25.0% vs. 11.2%?? P??0.01???? and few patients reached the standard of blood glucose monitoring ??12.1% vs.40.1%?? P??0.01?? and follow-up ??21.2% vs. 46.6%?? P??0.01??. The main reasons of DKA in group 1A were infection ??33.7%???? interrupting insulin therapy ??21.3%?? and eating disorder ??20.2%???? one patient had DKA after islet stem cell transplantation. Infection was also the major cause of DKA in group 1B ??4/10???? and 1 patient had DKA because of insulin bump failure. For DKA which occurred within different course?? the distribution of causes was different ??P??0.01??. Within 1 year of T1DM duration?? the major reason was interrupting insulin injection ??39.3%??. For patients more than 1 year?? it only accounted for 13.1%??8/61???? the major causes were infection ??22/61?? and eating disorder ??16/61??. The major cause in mutiple hospitals with high DKA frequency was infection ??50.0%???? while in other hospitals 28.1% of patients had DKA because of infection ??P??0.01??. Conclusion The frequency of DKA is 5.3%?? which is different in 12 hospitals?? with the highest up to 24.1%. Patients with DKA have poor glycemic control?? and they can not regularly monitor blood glucose and follow-up. We should emphasize the education of diabetes. Patients with insulin pump and islet stem cell transplantation must also become a new focus of education. Hospitals with high DKA frequency should give patients information how to deal with other diseases.     

1型糖尿病酮症酸中毒患儿缺氧诱导因子-1α与血管内皮细胞生长因子mRNA表达水平的变化

目的探讨1型糖尿病(T1DM)酮症酸中毒(DKA)患儿缺氧诱导因子-1α(HIF-1α)与血管内皮细胞生长因子(VEGF)mRNA水平的变化。方法天津市儿童医院住院T1DM并DKA患儿30例,于确诊24 h内(DKA 1组)及DKA纠正后10 d(DKA 2组)采血,另选取同期住院的不伴感染、缺氧、肿瘤或结缔组织病的同年龄同性别患儿30例为对照组。实时荧光定量PCR(Real-time PCR)法测定其外周血CD4+T淋巴细胞HIF-1α与VEGF mRNA的相对表达水平。PCR产物行琼脂糖凝胶电泳鉴定特异性。采用SPSS 13.0软件进行统计学分析。结果 3组HIF-1α及VEGF mRNA相对表达水平比较差异均有统计学意义(Pa<0.01)。DKA1组HIF-1α及VEGF水平明显高于对照组,差异有统计学意义(Pa<0.01);DKA纠正后HIF-1α及VEGF水平恢复,差异有统计学意义(P<0.05,0.01),但直至DKA纠正后10 d(DKA2组)仍未恢复至对照组水平,差异有统计学意义(P<0.01,0.05)。Real-timePCR产物行琼脂糖凝胶电泳,产物位于预期位置,确定产物特异性。结论 T1DM并DKA患儿CD4+T淋巴细胞HIF-1α与VEGFmRNA水平升高,且DKA纠正后HIF-1α与VEGF mRNA水平不能恢复至正常,这可能与T1DM并发症的发生发展有关。