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.     

胰岛素泵治疗儿童1型糖尿病酮症酸中毒32例临床分析

目的 观察胰岛素泵持续皮下注射胰岛素对儿童1型糖尿病酮症酸中毒(DKA)的疗效.方法 将2005-2008年收治的1型DKA患儿64例分为治疗组32例和对照组32例.治疗组予胰岛素泵治疗,对照组予小剂量胰岛素持续静脉滴注治疗.比较两组患儿血精变化、DKA纠正时间及住院时间.结果 治疗组血糖下降相对稳定,酸中毒纠正时间治疗组[(16.91±4.223)h]短于对照组[(23.31±3.797)h](P<0.001),且无反复.治疗过程中治疗组未出现低血糖,对照组出现1例.住院时间治疗组[(15.63±2.458)d]短于对照组[(20.88±3.348)d](P<0.001).结论 胰岛素泵持续皮下注射胰岛索治疗儿童1型糖尿病酮症酸中毒安全有效.     

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。     

Factors predicting cerebral edema in young children with diabetic ketoacidosis and new onset type I diabetes

We have attempted to identify any characteristics which could be used to predict the development of cerebral edema in four children under 5 years of age with new onset insulin-dependent diabetes mellitus and diabetic ketoacidosis. We retrospectively analysed and compared the concentration of serum sodium (corrected for serum glucose value) and effective serum osmolality of these 4 children with values of 10 age-matched controls with new onset insulin-dependent diabetes mellitus who did not develop cerebral edema during treatment of diabetic ketoacidosis. The initial serum sodium values of the two groups were not statistically different. Patients who developed cerebral edema had lower initial serum glucose values and effective serum osmolality. During treatment, patients who developed cerebral edema had consistently lower mean serum sodium and osmolality than controls at each 4-h interval after the first 4 h of therapy. Serum sodium and osmolality declined progressively after the initiation of therapy in cerebral edema patients, while remaining stable in controls. These data suggest that children who develop cerebral edema during treatment for diabetic ketoacidosis initially may have a relatively normal serum osmolality and subsequently develop progressive hyponatremia and/or a trend of declining serum sodium before developing cerebral edema.     

Current understanding and management of paediatric diabetic ketoacidosis

Diabetic Ketoacidosis (DKA) is a serious complication of insulin deficiency. It is typically seen in children and young people with Type 1 Diabetes Mellitus, either at first presentation, or in established disease, for instance due to poor compliance, equipment failure, or concurrent illness. Insulin deficiency leads to hyperglycaemia causing osmotic fluid loss, dehydration and electrolyte derangement. Osmotic symptoms of polyuria and polydipsia due to hyperglycaemia may give way to oliguria or anuria as circulatory insufficiency develops. Unable to utilise glucose, cells default to alternative mechanisms of energy production resulting in the accumulation of ketone bodies. Kussmaul breathing may compensate partially for the worsening acidosis. Untreated, DKA results in progressively worsening acidosis, development of shock, coma and ultimately death. Clear guidelines for the management of DKA in children and young people exist once a diagnosis is made. However, evidence for these guidelines is limited and remains the subject of ongoing debate. Diligence is required to ensure that fluid and insulin is delivered appropriately, and to identify early the complications of both DKA and its treatment, such as cerebral oedema. In this article we review the current state of DKA management with key practice points.     

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     

Rising incidence of type 1 diabetes mellitus in children and adolescents in Cyprus in 2000-2004

Introduction:  The incidence of type 1 diabetes mellitus (T1DM) has dramatically increased recently in some countries.
Aim:  To ascertain any changes in the incidence of T1DM in our population during the years 1990–2004.
Methodology:  All newly diagnosed cases of T1DM children under the age of 15 yr were registered and relevant information was obtained. Population demographic data based on the most recent census were used for calculations.
Results:  The overall mean annual incidence of T1DM during this 15-yr period was 11.9/100 000 person-years, with a statistically significant increase in the third 5-yr period (14.9/100 000 person-years).
The incidence during the first (1990–1994) and second (1995–1999) 5-yr periods was 10.5/100 000 person-years (p < 0.001). The overall male:female ratio was 0.94. Seasonal distribution for the first and second 5-yr periods revealed a higher incidence during winter and autumn months. Seasonal variation, however, disappears in the third 5-yr period, where no differences were found between the four seasons.
Conclusion:  The incidence of newly diagnosed T1DM cases has increased during 2000–2004. A seasonal variation during the first and second 5-yr periods was no longer observed in the third 5-yr period.     

儿童初发1型糖尿病伴不同程度糖尿病酮症酸中毒与甲状腺功能相关性研究

目的 分析初发1型糖尿病（T1DM）患儿伴发糖尿病酮症酸中毒（DKA）的严重程度与甲状腺功能状态的相关性。方法 回顾性分析2015年1月至2020年12月内分泌遗传代谢科收治的167例初发T1DM患儿临床资料,比较T1DM患儿中非DKA,轻度、中度、重度DKA四组临床特点、实验室指标、甲状腺功能状态差异,分析血清游离三碘甲状腺原氨酸（FT₃）水平的影响因素。结果 167例初发T1DM患儿中,男81例、女86例,中位年龄6.5（4.0～9.9）岁,中位病程14.0（7.0～28.0）d,非DKA组104例、轻度DKA组20例、中度DKA组16例、重度DKA组27例。各DKA组（FT₃）、总三碘甲状腺原氨酸（TT₃）、总甲状腺素（TT₄）、pH值及HCO^-₃显著低于非DKA组,而阴离子间隙（AG）、血糖水平显著高于非DKA组;重度DKA组的白细胞计数、中性粒细胞百分比显著高于其他三组,差异均有统计学意义（P<0.05）。167例初发T1DM儿童中,甲状腺...     

HLA-DRB1*08 allele may help to distinguish between type 1 diabetes mellitus and type 2 diabetes mellitus in Mexican children

BACKGROUND: It may be difficult to distinguish type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM) in the pediatric population. Autoantibodies may help to differentiate both types of diabetes, but sometimes these are positive in patients with T2DM and negative in patients with T1DM. The human leukocyte antigen (HLA)-DR genotype has been associated with T1DM and with T2DM only in adults and in determined cases. AIM: To determine the differences in HLA class II allele frequencies in Mexican children with T1DM and T2DM. METHODS: We included 72 children with T1DM, 28 children with T2DM, and 99 healthy controls. All were Mexican, and diabetes was diagnosed according to the clinical and laboratory criteria established by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. The HLA-DRB1 typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probe and polymerase chain reaction sequence-specific primers. RESULTS: We found an increased frequency of HLA-DRB1*08 and a decreased frequency of HLA-DRB1*04 in the group with T2DM vs. T1DM [p = 0.0001, odds ratio (OR) = 10.58, 95% confidence interval (CI) = 3-40.8 and p = 0.0006, OR = 0.24, 95% CI = 0.11-0.53, respectively]. No significant differences were found between HLA-DRB1 alleles in T2DM vs. controls. In the group with T1DM, there was a significantly increased frequency of the HLA-DR4 and HLA-DR3 alleles relative to controls (p = 0.0000001, OR = 3.59, 95% CI = 2.2-5.8 and p = 0.00009, OR = 4.66, 95% CI = 2.1-10.3, respectively). CONCLUSION: There are significant differences in the HLA profile in Mexican children with T1DM and T2DM. HLA typing could play a role in the differentiation between both types of diabetes in this population.     

New-onset diabetes mellitus presenting with diabetic ketoacidosis after pediatric liver transplantation

Abstract:  The development of NODM is a common metabolic complication after liver transplantation. Presentation of post-liver transplant diabetes mellitus with DKA is rare especially among pediatric patients. We reported three pediatric patients who presented with DKA after liver transplantation. The underlying diseases leading to transplantation were cryptogenic liver cirrhosis, Wilson disease, and congenital hepatic fibrosis. None of the three patients had a history of diabetes prior to transplantation and all of them were cases of NODM after transplantation. All three patients presented with severe hyperglycemia, significant ketosis, and metabolic acidosis of variable severity. All of them received tacrolimus as one of the immunosuppressant agents. The patients received a liver transplant from a DD. The patients were treated with intravenous insulin injection (0.1 U/kg/h) and recovered from DKA, but one case expired in the intensive care unit because of bacterial sepsis after recovery from DKA. Our experience suggests that PTDM may result in ketoacidosis, and we emphasize the importance of paying more attention to glucose metabolism and risk of diabetes mellitus in patients with immunosuppressive therapy, especially tacrolimus.     

Chromium levels in healthy and newly diagnosed type 1 diabetic children

Background: The aim of this study was to compare the chromium levels of plasma (PCL), erythrocyte (ECL) and urine (UCL) in type 1 diabetics and healthy subjects and to review the relation between metabolic parameters. Methods: We evaluated 165 subjects who were: newly diagnosed type 1 diabetics (group 1 [n= 29]); previously diagnosed type 1 diabetics (group 2 [n= 18]); non‐diabetic control subjects who were admitted and treated for any reason in hospital (group 3 [n= 21]); and two other groups of control subjects from two schools that have different socioeconomic levels (group 4 [n= 48] and group 5 [n= 49]). Results: PCL in group 1 and group 2 subjects (7.21 ± 4.78 and 10.94 ± 3.04 mcg/L, respectively) was significantly lower than in all control groups (21.84 ± 7.87, 16.11 ± 7.44, 17.25 ± 8.58 mcg/L, respectively) (P < 0.05). A significant difference in PCL between the group 1 and group 2 subjects was present (7.21 ± 4.78 and 10.94 ± 3.04, respectively) (P= 0.021). ECL (as tissue chromium) in group 1 and group 2 subjects (13.99 ± 11.37 and 19.64 ± 12.58, respectively) was significantly lower than in all control groups (28.20 ± 7.34.25, 49 ± 12.47, 26.37 ± 9.77 mcg/L, respectively) (P= 0.05). UCL in group 1 and group 2 subjects (11.44 ± 6.88 and 15.68 ± 6.75 mcg/L, respectively) was significantly lower than in group 3 subjects (28.83 ± 9.37mcg/L) (P < 0.05). There were significant correlations between length, bodyweight and PCL in the group 1 subjects (r = 0.42, P= 0.22 and r = 0.53, P= 0.03, respectively). There was a negative correlation between plasma glucose and UCL, which was not statistically significant in group 2 subjects (r =?0.4, P= 0.061). Conclusion: There was a negative chromium balance in type 1 diabetics. This negative balance may affect the insulin function badly. If this negative balance should be confirmed by recent studies we suggest that chromium supplementation with insulin is necessary for type 1 diabetes.     

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.     

新发儿童1型糖尿病酮症酸中毒与重症儿童应激性高血糖的鉴别诊断

目的 探讨新发儿童1型糖尿病酮症酸中毒与重症儿童应激性高血精的鉴别诊断指标.方法 前瞻性研究30例1型糖尿病酮症酸中毒(DKA组)患儿[年龄(6.5±3.6)岁]和20例重症应激性高血糖(SHG组)患儿[年龄(5.8±3.1)岁]的鉴别诊断指标,分别比较两组糖化血红蛋白(HbAlc)、空腹血糖(FBG)、二氧化碳结合力(CO_2-CP)、阴离子间隙(AG)、空腹C-肽(FCP)、空腹胰岛素(FINS)、胰岛素抵抗指数(IRI)、皮质醇(COR)及是否依赖胰岛素治疗.对照组(C组)30例为健康体检儿童,年龄(6.1±3.4)岁.结果 DKA组和SHG组均有高血糖、AG和皮质醇升高.CO_2-CP降低.DKA组HbAlc显著高于正常对照和SHG组(P均<0.001),DKA组HbAlc>7.3%,SHG组HbAlc<6.5%.FINS、FCP及IRI在DKA组均显著低于SHG组和对照组(P均<0.001),DKA组FINS<2.6 U/L,FCP<0.16μg/L,IRI<2.7(mmol·U./L);SHG组FINS>9.3 U/L,FCP>0.9mg/L,IRI>5.3(mmol·U/L).SHG组对胰岛素无依赖性,而DKA组需依赖胰岛素才能控制血糖.结论 HbAlc、FINS、FCP及IRI是鉴别DKA和SHG的简便、良好的指标.DKA组HbAlc显著升高,FINS、FCP及IRI均显著降低;SHG组FINS、FCP及IRI均显著升高,HbAlc<6.5%.且DKA的治疗依赖胰岛素,而SHG组治疗不依赖胰岛素.