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。     

1型糖尿病患儿反复发生酮症酸中毒的原因

目的　分析 1型糖尿病患儿反复发生酮症酸中毒 (DKA)的原因。方法　回顾总结 2 0年来在我院诊治的 1型糖尿病患儿 85 0例次 ,其中因DKA住院 2 2 5例次 ,2次或 2次以上者 5 6例 ,131例次 ,将其分为前 10年和后 10年两组进行分析。结果　两组DKA患儿占总糖尿病人数比率及反复发生DKA人数相比有显著差异 ,后 10年显著少于前 10年 (P <0 .0 1)。在诱因方面感染占第 1位 ,平均 71.8% ;不控制饮食而暴饮暴食 19% ;因停用胰岛素 9.2 % ,两组相比无显著差异 (P >0 .0 5 )。结论　对糖尿病病人进行系统的管理和教育是降低DKA发生率的重要手段     

Ketoacidosis at onset of type 1 diabetes mellitus in children--frequency and clinical presentation

Abstract: Background: Since 1987, patients with newly diagnosed diabetes mellitus type 1 under 15 yr of age have been registered in Baden‐Wuerttemberg (BW), Germany. Aim: Our aim was to describe the frequency and the clinical presentation of diabetic ketoacidosis (DKA) at onset of type 1 diabetes mellitus in children. Methods: All 31 pediatric departments in BW and one diabetes center participated in this study. Hospital records of 2121 children below 15 yr of age were examined retrospectively. DKA was defined as glucose > 250 mg/dL, pH < 7.30 or bicarbonate < 15 mmol/L and ketonuria. Statistical analysis was done after logarithmic transformation. Results: 26.3% (n = 558) of all patients presented with DKA. The mean age of these patients was 7.9 yr. The frequency of DKA is higher in girls than in boys (28.9 vs. 23.8%; p = 0.0079). Those aged 0–4 yr suffered most frequently (p < 0.0001) from ketoacidosis (36.0%). The percentage of DKA in newly diagnosed cases was constant over 10 yr. 23.3% of all patients with DKA presented with an altered level of consciousness; 10.9% of these had clinical signs of coma. No deaths occurred. The proportion of ketoacidosis does not increase concurrently with the number of diabetes manifestations in winter. Conclusion: The proportion of DKA in children with newly diagnosed diabetes mellitus is significant. In particular, children < 5 yr and girls face an increased risk. DKA may be the result of a particularly aggressive subtype of diabetes.     

The changing presentation of children with newly diagnosed type 1 diabetes mellitus

Abstract: Although it is known that the incidence of type 1 diabetes mellitus (DM) in childhood is progressively increasing, it is less clear whether the presentation of newly diagnosed DM is changing. The aim of this study was to establish whether any biochemical or clinical presentation parameters have altered over time.
A retrospective study was performed comparing newly diagnosed children with DM in two 24 month time intervals, 8 yrs apart (1988–89 and 1995–96). Fifty-seven children were diagnosed with type 1 DM in 1988–89 and 70 children in 1995–96. At presentation, children born in the later cohort had a higher pH (p < 0.001) and lower serum glucose (p < 0.05). Although the frequency of diabetic ketoacidosis (DKA) was higher in the 1988/89 cohort (63% vs. 42% in 1995/96) the absolute number of children with DKA in each time interval was similar (33 subjects in 1988–89 vs. 30 subjects in 1995/96). Islet cell antibody (ICA) levels were very different between the two cohorts; higher antibody levels were found in the 1988/89 group (p < 0.01). DKA was also associated with higher ICA titres (p < 0.05). Hospital admission stay decreased from 6.5 DS to 3.4 DS over the 8-year period (p < 0.0001).
At our institution, the presentation of children with type 1 D M is changing with many more children diagnosed before developing DKA. We speculate that a new environmental factor(s) may be responsible for the absolute increase in patients presenting without DKA, while older etiologies (both genetic and environmental) are responsible for the steady, unchanging number of patients with a more severe presentation. Greater awareness of diabetes in children is not the factor contributing to earlier diagnosis before DKA develops.     

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.     

Factors associated with childhood diabetes manifesting as ketoacidosis and its severity]

INTRODUCTION: Type 1 diabetes in children in France is frequently diagnosed at the stage of ketoacidosis (DKA). PATIENTS AND METHODS: A prospective study was performed in a group of 72 children (mean age = 9.4 years) at onset of diabetes, in order to determine which factors were associated to DKA and to the severity of DKA (pH < 7.10) at diagnosis. RESULTS: Younger age was related to DKA (p = 0.03), but not to its severity. A lesser frequency of DKA was found in children with a family history of insulin-treated diabetes ( p = 0.04). Misdiagnosis was more frequently observed in children with DKA than in children without DKA (p = 0.02) and in case of severe DKA at admission by comparison with non severe cases (76 vs 23%; p = 0.002). Children in low economic intake families exhibited more frequently a severe DKA (77 vs 23%; p = 0.002) and were more frequently misdiagnosed before admission (48% vs 10%; p < 0.01). Urine strips for glucose and ketone determinations were underused for diagnosis before admission (15% only). CONCLUSION: Those results underline the need to both inform physicians and ameliorate the access to health care for low social class families, in order to take up the challenge of reducing the incidence of DKA at diagnosis in diabetic children in our country.     

Ketoacidosis at diagnosis of type 1 diabetes: Effect of prospective studies with newborn genetic screening and follow up of risk children

We studied the frequency of diabetic ketoacidosis (DKA) in children at diagnosis of type 1 diabetes (T1D) in a region where newborn infants have since 1995 been recruited for genetic screening for human leukocyte antigen (HLA)‐conferred disease susceptibility and prospective follow up. The aim was to study whether participation in newborn screening and follow up affected the frequency of DKA, and to follow the time trends in DKA frequency. We first included children born in Oulu University Hospital since 1995 when the prospective studies have been ongoing and diagnosed with T1D <15 years by 2015 (study cohort 1, n = 517). Secondly, we included all children diagnosed with T1D <15 years in this center during 2002‐2014 (study cohort 2, n = 579). Children who had an increased genetic risk for T1D and participated in prospective follow up had low frequency of DKA at diagnosis (5.0%). DKA was present in 22.7% of patients not screened for genetic risk, 26.7% of those who were screened but had not an increased risk and 23.4% of children with increased genetic risk but who were not followed up. In study cohort 2 the overall frequency of DKA was 18.5% (13.0% in children <5 years, 14.0% in children 5‐10 years and 28.6% in children ≥10 years at diagnosis; P<.001). In children <2 years the frequency of DKA was 17.1%. Participation in prospective follow‐up studies reduces the frequency of DKA in children at diagnosis of T1D, but genetic screening alone does not decrease DKA risk.     

Prävalenz von Ketoazidosen bei Manifestation des Diabetes mellitus Typ 1 in einem Zentrum für pädiatrische Diabetologie

Introduction. Diabetic ketoacidosis (DKA) is still the most serious complication of the newly diagnosed child with diabetes mellitus type 1 because it is still the most common cause of death due to cerebral edema. Methods. All patient records of children with new diagnosed type 1 diabetes mellitus in the children's hospital of the University of Leipzig in 1995 to 1999 were analysed retrospectively. Results. 31 patients (29,8%) had DKA, 10 of which were unconscious or somnolent. In those children and adolescents with DKA blood glucose levels, glycosylated hemoglobin levels and initial insulin requirement were higher and the duration of hospital stay was longer. The rate of remission was lower in the DKA group (67 vs. 80.8%). A delayed or false diagnosis was reported in 14% of patients without but in 22,5% of the children and adolescents with DKA. Conclusion. To improve the rate of remission and reduce the hospital stay at the onset of diabetes mellitus the rate of DKA must be reduced due to better information about symptoms of diabetes mellitus in the general population and especially among general practitioners and pediatricians.     

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。     

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.     

Characteristics at diagnosis of type 1 diabetes in children younger than 6 years

OBJECTIVE: To characterize the prodrome, presentation, family history, and biochemical status at diagnosis of type 1 diabetes mellitus (T1D) in children under age 6 years. STUDY DESIGN: This was a retrospective chart review of patients hospitalized at diagnosis with T1D from 1990 to 1999 in a children's hospital. RESULTS: A total of 247 children were hospitalized, 44% of whom presented in diabetic ketoacidosis (DKA). When stratified by 2-year age intervals, only total carbon dioxide (tCO(2)) was significantly lower in the youngest children (P = .02), and the duration of candidiasis was significantly longer in those children presenting in DKA (P = .004). Parents were more likely to recognize symptomatic hyperglycemia in children older than 2 years (P < .0001). Most parents sought care for their child suspecting that the child had diabetes; the other children were diagnosed when presenting with another concern. Only gender and tCO(2) were significantly correlated with hemoglobin A1c (HbA1c); age-adjusted HbA1c was 0.64% higher in girls compared with boys (P = .045), and each 1-mmol/L decrement in tCO(2) increased the age- and gender-adjusted HbA1c by 0.086% (P < .001). CONCLUSIONS: A high proportion of children under age 6 years present critically ill at the diagnosis of T1D. When any of the classic symptoms of diabetes or a yeast infection is present, a serum glucose level should be measured.     

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.     

Clinical features at the onset of childhood type 1 diabetes mellitus in Shenyang,China

Aim: To describe the clinical picture and laboratory features of Chinese children with newly diagnosed type 1 diabetes mellitus. Methods: The clinical and laboratory data of a total of 203 children who presented with newly diagnosed type 1 diabetes mellitus during a 5‐year period (2004–2008) were retrospectively analysed based on hospital records. Results: There were 88 boys (43.3%) and 115 girls (56.7%) with a median age of 8.3 years. The age distribution was categorised as 0–4 years: 52 (25.6%), 5–9 years: 57 (28.1%) and 10–14 years: 94 (46.3%). We found a peak incidence rate in the older age group. No significant seasonality was observed. The most common symptoms were polydipsia, polyuria and weight loss. Eighty‐five (41.9%) of all patients presented with diabetic ketoacidosis (DKA). The average duration of presenting symptoms before the hospital encounter was 24.5 days. Young age group children had shorter duration (17.1 days, P= 0.03) and significantly lower levels of C‐peptide (P= 0.003) and haemoglobin A1c (P= 0.049) than the other groups. Children with DKA had a higher incidence of preceding infections (P= 0.032), lower free triiodothyronine and free thyroxine levels (P= 0.035, 0.046), and higher white blood cell counts (P= 0.000) than the non‐DKA group. Conclusion: The duration between the onset of the symptoms and diagnosis was long, and the proportion of DKA in children with newly diagnosed diabetes mellitus was high. These findings call for a collaborative effort for the early recognition of symptoms by patients and physicians in order to avoid more severe types of presentation.     

Mechanism of cerebral edema in children with diabetic ketoacidosis

OBJECTIVES: Cerebral edema during diabetic ketoacidosis (DKA) has been attributed to osmotic cellular swelling during treatment. We evaluated cerebral water distribution and cerebral perfusion during DKA treatment in children. STUDY DESIGN: We imaged 14 children during DKA treatment and after recovery, using both diffusion and perfusion weighted magnetic resonance imaging (MRI). We assessed the apparent diffusion coefficients (ADCs) and measures reflecting cerebral perfusion. RESULTS: The ADC was significantly elevated during DKA treatment (indicating increased water diffusion) in all regions except the occipital gray matter. Mean reductions in the ADC from initial to postrecovery MRI were: basal ganglia 4.7 +/- 2.5 x 10(-5) mm(2)/s (P=.002), thalamus 3.7 +/- 2.8 x 10(-5) mm(2)/s, (P=.002), periaqueductal gray matter 4.3 +/- 5.1 x 10(-5) mm(2)/s (P=.03), and frontal white matter 2.0 +/- 3.1 x 10(-5) mm(2)/s (P=.03). In contrast, the ADC in the occipital gray matter increased significantly from the initial to postrecovery MRI (mean increase 3.9 +/- 3.9 x 10(-5) mm(2)/s, P=.004). Perfusion MRI during DKA treatment revealed significantly shorter mean transit times (MTTs) and higher peak tracer concentrations, possibly indicating increased cerebral blood flow (CBF). CONCLUSIONS: Elevated ADC values during DKA treatment suggests a vasogenic process as the predominant mechanism of edema formation rather than osmotic cellular swelling.     

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.     

The risk and outcome of cerebral oedema developing during diabetic ketoacidosis.

BACKGROUND: Cerebral oedema is a major cause of morbidity and mortality in children with insulin dependent diabetes. AIMS: To determine the risk and outcome of cerebral oedema complicating diabetic ketoacidosis (DKA). METHODS: All cases of cerebral oedema in England, Scotland, and Wales were reported through the British Paediatric Surveillance Unit between October 1995 and September 1998. All episodes of DKA were reported by 225 paediatricians identified as involved in the care of children with diabetes through a separate reporting system between March 1996 and February 1998. Further information about presentation, management, and outcome was requested about the cases of cerebral oedema. The risk of cerebral oedema was investigated in relation to age, sex, seasonality, and whether diabetes was newly or previously diagnosed. RESULTS: A total of 34 cases of cerebral oedema and 2940 episodes of DKA were identified. The calculated risk of developing cerebral oedema was 6.8 per 1000 episodes of DKA. This was higher in new (11.9 per 1000 episodes) as opposed to established (3.8 per 1000) diabetes. There was no sex or age difference. Cerebral oedema was associated with a significant mortality (24%) and morbidity (35% of survivors). CONCLUSIONS: This first large population based study of cerebral oedema complicating DKA has produced risk estimates which are more reliable and less susceptible to bias than those from previous studies. Our study indicates that cerebral oedema remains an important complication of DKA during childhood and is associated with significant morbidity and mortality. Little is known of the aetiology of cerebral oedema in this condition and we are currently undertaking a case control study to address this issue.     

Serum IL-1, IL-2, TNFalpha and INFgamma levels of patients with type 1 diabetes mellitus and their siblings

Type 1 diabetes mellitus (DM) develops as a result of autoimmune destruction of the pancreatic beta-cells. The aim of this study was to explore possible associations between serum levels of cytokines, IL-1, IL-2, TNFalpha and INFgamma and metabolic parameters in children with type 1 DM and their non-diabetic siblings to determine whether these cytokines could be indicators of disordered immune regulation. The study population consisted of 41 children with type 1 DM, 32 non-diabetic siblings, and 28 healthy controls. Children with DM were divided into three subgroups: 1) newly diagnosed patients with diabetic ketoacidosis (ND + DKA), 2) newly diagnosed patients without DKA (ND - DKA), and 3) previously diagnosed patients (PD). The highest serum IL-1alpha level was found in the ND - DKA group, which was significant compared to both the ND + DKA (p < 0.05) and the siblings (S) (p < 0.005). IL-2 levels were similar among all groups. The highest TNFalpha level was observed in the ND + DKA group, which was significant against the ND - DKA (p < 0.05), PD (p < 0.001), S (p < 0.05), and control (C) (p < 0.005) groups. TNFalpha concentration in the PD group was significantly lower than those of S (p< 0.005) and C (p < 0.001) groups. The ND - DKA group had the highest INFgamma and this was statistically significant when compared with the S (p < 0.005) and C (p < 0.05) groups. Both the newly diabetics and all diabetics as a group had statistically significantly higher INFgamma levels than both the S (p < 0.01 for both) and C (p < 0.05 for both) groups. In the diabetics as a whole group, TNFalpha showed correlations with INFgamma (r = 0.370, p < 0.05). IL-1 showed correlation with TNFalpha (r = 0.368, p < 0.05) INFgamma (r = 0.796, p < 0.001) and IL-2 (r = 0.862, p < 0.001) in the all diabetics group. IL-2 was correlated with TNFalpha (r = 0.320, p < 0.05) and INFgamma (r = 0.754, p < 0.01) in the all diabetics group. In conclusion, our results suggest that proinflammatory cytokines TNFalpha, INFgamma, IL-1alpha and IL-2 may play important roles alone or in combination in the pathogenesis of type 1 diabetes mellitus.     

Serum interleukin-18 levels are raised in diabetic ketoacidosis in Chinese children with type 1 diabetes mellitus

OBJECTIVE: To investigate the role of serum interleukin (IL-18) in children with type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis (DKA). DESIGN: Case-control study. SUBJECTS: Sixty-one children with T1DM including 28 with DKA and 33 without DKA and 30 age - and sex-matched healthy controls were recruited. METHODS: Serum IL-18, IL-12, and IFN-gamma levels were measured in all subjects by enzyme linked immunosorbent assay. RESULTS: Serum IL-18 levels were significantly higher in patients with DKA than those in patients without DKA (759.2 +/- 353.8 pg/mL vs. 634.9 +/- 399.7 pg/mL, P = 0.001) and healthy controls (310.0 +/- 265.3 pg/mL). The serum IL-12 and IFN-gamma levels were not different between patients and controls (277.5 +/- 207 pg/mL vs. 351.4 +/- 223.4 pg/mL, P = 0.45 and 7.02 +/- 7.53 pg/mL vs. 5.59 +/- 5.34 pg/mL, P = 0.21, respectively). CONCLUSION: Serum IL-18 levels are increased in children with type 1 diabetes mellitus and could be a predictor of diabetic ketoacidosis.     

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。