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.     

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.     

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.     

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.     

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.     

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.     

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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.     

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。     

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.     

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.     

Evaluation of glucose intolerance in adolescents relative to adults with type 2 diabetes mellitus

AIM: There is an increasing trend in the prevalence of type 2 diabetes mellitus (DM2) in childhood and adolescence, while positive family history of DM2 and obesity are the most important risk factors. To study the influence of family history and obesity on glucose intolerance in our country was the aim of this study. STUDY DESIGN AND METHODS: A total of 105 children and adolescents aged 10-18 years (mean 13.3 +/- 2.5 years) were included in the study. All children and adolescents were divided into three groups according to positive family history of DM2 and obesity, and an oral glucose tolerance test (OGTT) was performed for all. Prediabetes was defined as impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG). Insulin secretion and insulin resistance were estimated using the insulinogenic index; and the homeostatic model assessment for insulin resistance (HOMA-IR) and Matsuda index, respectively. RESULTS: The prevalence of prediabetes was 15.2% in the whole group, while it was 25.5% in obese children who also had a positive family history of DM2. The frequency of hyperinsulinism was 57.1% in all groups. Prediabetic children had significant insulin resistance (HOMA-IR 11.5 +/- 7.1 and 4.1 +/- 6.4, respectively, p = 0.034). CONCLUSIONS: Obesity and glucose intolerance are also a problem in developing countries. The risk of prediabetes in children is highest in obese children who also have a positive family history of DM2. There is a need for a lifelong preventive program starting in childhood to avoid DM2 and decrease cardiovascular risk factors     

Impaired beta-cell and alpha-cell function in African-American children with type 2 diabetes mellitus--"Flatbush diabetes"

The incidence of type 2 diabetes mellitus (T2DM) in children and adolescents has substantially increased over the past decade. This is attributed to obesity, insulin resistance and deficient beta-cell function. In children a pubertal increase in insulin resistance and an inability to mount an adequate beta-cell insulin response results in hyperglycemia. Adults with T2DM have a diminished first phase response to intravenous glucose and a delayed early insulin response to oral glucose. Long-term studies show progressive loss of beta-cell function in T2DM in adults; however, such long-term studies are not available in children. To characterize beta- and alpha-cell function in African-American adolescents with established T2DM, we used mixed meal, intravenous glucagon and oral glucose tolerance testing and compared them to obese non-diabetic controls. T2DM was defined as fasting C-peptide >0.232 nmol/l and absent autoimmune markers. BETA-CELL FUNCTION: Meal testing in 24 children and adolescents with T2DM, mean age 14 years, BMI 30 kg/m2, Tanner stage II-V, HbA1c 8.9%, were compared with BMI- and age-matched controls. Forty percent presented with DKA. Half were treated with insulin and half with diet/oral anti-diabetic agents. Although absolute C-peptide response in both groups was similar, the incremental rise in C-peptide relative to plasma glucose in the patients with T2DM compared to controls was 40% and 35% lower 30 and 60 min after the meal, p <0.007 and p <0.026. Glucagon testing in 20 pediatric patients with T2DM compared with 15 matched controls showed significantly lower 6 min stimulated C-peptide relative to the ambient plasma glucose in patients with T2DM compared to controls (0.039 +/- 0.026 vs 0.062 +/- 0.033, p <0.05). The clinical utility is that 78% of patients with a 6 min C-peptide <1.4 nmol required insulin, while 81% of those >1.4 nmol required oral anti-diabetic agents, p <0.0001. Furthermore, the duration of T2DM up to 5 years after diagnosis was associated with lower fasting and glucagon-stimulated C-peptide levels, implying worsening beta-cell function over time, even in children and adolescents. ALPHA-CELL FUNCTION: During meal testing, children and adolescents with T2DM had less suppression of plasma glucagon than non-diabetic controls; this was more severe with longer duration of T2DM and poorer glycemic control. BETA-CELL RECOVERY: In African-American and Hispanic adults, intensive treatment of blood glucose may achieve beta-cell recovery with 35-40% of newly diagnosed patients going into remission after 6 months treatment. They remain off anti-diabetic pharmacological agents in remission for a median of over 3 years with normal HbA1c levels. We hypothesize this to be due to removal of a critical component of glucose or lipotoxicity at the level of the beta-cell and/or peripheral tissue. Four of 20 African-American children presenting with mean glucose 650 mg/dl maintained normal HbA1c levels on small doses of metformin after initial treatment with multiple insulin injections with or without metformin. This suggests a marked recovery of beta-cell function, similar to that in adults. SUMMARY: T2DM in children, as in adults, is characterized by insulin deficiency relative to insulin resistance. Plasma C-peptide levels may be clinically useful in guiding therapeutic choices, since patients with lower levels required insulin treatment; beta-cell function is also diminished with longer duration of T2DM. The possibility exists that in children, as in adults, intensive glycemic regulation may allow for beta-cell recovery and preservation. Thus, optimum beta- and alpha-cell function are central to the prevention of DM and maintenance of good glycemic control in African-American and Hispanic children and adolescents with T2DM.     

Polyunsaturated fatty acids in plasma lipids of diabetic children during and after diabetic ketoacidosis

BACKGROUND AND AIM: Previously we reported significantly higher plasma values of the essential fatty acids but significantly lower values of their longer-chain metabolites in diabetic children than in healthy controls. Here, we report data on the acute effect of diabetic ketoacidosis (DKA) on the fatty acid composition of plasma lipids. METHODS: Diabetic children (n=9; age: 16.1 [3.3] y; duration of diabetes: 5.0 [5.3.] y; daily insulin dose: 0.87 [0.66] unit/kg body weight/d; glycated haemoglobin: 13.4 [2.8] %; median [IQR]) were investigated at admission for DKA (during DKA) and at the end of the treatment of DKA (after DKA). Fatty acid composition of plasma lipid classes was determined by high-resolution capillary gas-liquid chromatography. RESULTS: Blood glucose (27.0 [8.5] vs 6.5 [1.6] mmol/l), pH (7.28 [0.35] vs 7.36 [0.06]) and base excess (-8.9 [15.1] vs -2.2 [6.3] mmol/l) were grossly abnormal during but not after DKA. Values of linoleic acid were significantly lower after than during DKA (non-esterifed fatty acids (NEFA): 15.55 [1.47] vs 12.27 [5.74] % wt/wt; triacylglycerols (TG): 20.84 [9.23] vs 17.40 [5.78]; p<0.05). In contrast, values of gamma-linolenic acid (NEFA: 0.87 [0.54] vs 2.34 [1.85]; p<0.05) and arachidonic acid (TG: 1.37 [0.71] vs 1.74 [0.57]; p<0.05) were significantly lower during than after DKA. The product/substrate ratios for delta-6 desaturation were significantly lower during than after DKA. CONCLUSION: Successful treatment of diabetic ketoacidosis is associated with a significant increase of long-chain polyunsaturated fatty acid values in blood plasma in diabetic children. This observation suggests that disturbances of essential fatty acid metabolism in diabetic children are related not only to diet but to hypoinsulinaemia as well.     

Changing spectrum of diabetes mellitus in children: challenges with initial classification

Objective. To determine the frequency of initial misclassification of diabetes mellitus (DM) in children and to compare the presenting features of DM1, DM2, and the misclassified cases. Results. A total of 206 patients fulfilled the inclusion criteria. Of them, 74.75% had DM1 and 25.25% had DM2. Ten percent of studied patients had a subsequent change in classification. The mean HbA1c of the DM2 patients, who were initially misclassified, was 13.35% (SD = 1.96). The mean HbA1c of DM2 patients with correct initial classification was 8.83% (SD = 3.01). Diabetes ketoacidosis (DKA) was seen in 59.44% of DM1 and 23.91% of DM2 patients. Of the DM2 patients who were initially misclassified, 58.82% had presented in DKA as opposed to only 6.45% of patients who were correctly classified. Conclusion. The initial classification of DM frequently requires revision (10% in this study). The misclassification is highest among DM2 patients who initially present with higher HbA1c and DKA.     

Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy

Brufani C, Ciampalini P, Grossi A, Fiori R, Fintini D, Tozzi A, Cappa M, Barbetti F. Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy. Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). Aims: Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. Methods: The study group included 510 overweight/obese subjects (3–18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA‐IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta‐cell function was estimated by insulinogenic index. Fat mass was measured by dual‐energy x‐ray absorptiometry. Results: Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA‐IR and glucose‐stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA‐IR = 4.4 ± 2.5 vs. 3.4 ± 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. Conclusions: Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents.     

The association between ketoacidosis and 25(OH)-vitamin D levels at presentation in children with type 1 diabetes mellitus

Background:  There is considerable evidence supporting the role of vitamin D deficiency in the pathogenesis of type 1 diabetes mellitus (T1DM). Vitamin D deficiency is also associated with impairment of insulin synthesis and secretion. There have been no formal studies looking at the relationship between 25(OH)-vitamin D₃ and the severity of diabetic ketoacidosis (DKA) in children at presentation with T1DM.
Objective:  To determine the relationship between measured 25(OH)-vitamin D₃ levels and the degree of acidosis in children at diagnosis with T1DM.
Subjects:  Children presenting with new-onset T1DM at a tertiary children's hospital.
Methods:  25(OH)-vitamin D₃ and bicarbonate levels were measured in children at presentation with newly diagnosed T1DM. Those with suboptimal 25(OH)-vitamin D₃ levels (<50 nmol/L) had repeat measurements performed without interim vitamin D supplementation.
Results:  Fourteen of the 64 children had low 25(OH)-vitamin D₃ levels at presentation, and 12 of these had low bicarbonate levels (<18 mmol/L) (p = 0.001). Bicarbonate explained 20% of the variation in vitamin D level at presentation (partial r² = 0.20, p < 0.001) and ethnic background a further 10% (partial r² = 0.10, p = 0.002). The levels of 25(OH)-vitamin D₃ increased in 10 of the 11 children with resolution of the acidosis.
Conclusions:  Acid–base status should be considered when interpreting 25(OH)-vitamin D₃ levels in patients with recently diagnosed T1DM. Acidosis may alter vitamin D metabolism, or alternatively, low vitamin D may contribute to a child's risk of presenting with DKA.     

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.     

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。     

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.     

Partial remission phase of diabetes in children younger than age 10 years

There is renewed interest in the phase of partial remission in recently diagnosed diabetes because of the potential for pharmacological and immune intervention to preserve beta cell function. 95 children younger than 10 years were investigated to assess the influence of age, sex, diabetic ketoacidosis (DKA), admission at diagnosis, and ethnicity on the frequency of remission and insulin requirements during the first two years after diagnosis. Partial remission was defined as a requirement of insulin < 0.5 U/kg body weight/day. There was partial remission in 41 patients, with no differences for children aged 2-4 years and those aged 5-9 years. None of the five children aged < 2 years remitted. Forty five of 95 children were admitted to hospital at diagnosis, of whom 26 of 45 had DKA (blood pH < 7.25). In this number of children we were unable to show a statistical difference in the rate of remission with respect to DKA, admission to hospital at diagnosis, sex, or South Asian ethnic background. There were no differences in insulin requirements between the different groups by the end of two years and at that time seven of the children required insulin < 0.5 U/kg/day. The results suggest that even in preschool children there is potential for attempting to preserve beta cell function.