Showing papers in "Pediatric Diabetes in 2010"

Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth Study

Abstract: Liu LL, Lawrence JM, Davis C, Liese AD, Pettitt DJ, Pihoker C, Dabelea D, Hamman R, Waitzfelder B, Kahn HS. Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth Study. Objective: Obesity's association with type 2 diabetes (T2DM) is well established, but is less clear with type 1 diabetes (T1DM). We calculated the prevalence of overweight and obesity among diabetic youth in the USA from a six-center, population-based study of racially and ethnically diverse youth with diabetes, and we compared these rates with estimates among nondiabetic youth. Design/setting: Diabetic participants were examined in 2001−2004 for the SEARCH for Diabetes in Youth study (SEARCH) and nondiabetic participants were examined during the same years of the National Health and Nutrition Examination Survey (NHANES). Participants: 3953 diabetic youth and 7666 nondiabetic youth aged 3−19 yr. Main outcome measures: Overweight was defined as body mass index (BMI) from the 85th to <95th percentile for age and sex and obesity defined as ≥95th percentile. Diabetes type was categorized as T1DM or T2DM based on physician diagnosis. Results: Among youth with T2DM, the prevalence of overweight was 10.4% and obesity was 79.4%. Among youth with T1DM, 22.1% were overweight. The prevalence of overweight among youth with T1DM was higher than among those without diabetes overall (22.1% vs. 16.1%) (P <.05). The obesity rate for T1DM was 12.6% overall (range Non-Hispanic White 10.7%−African-American 20.1%). Conclusions: As expected, most of the youth with T2DM were obese. Youth with T1DM had a higher prevalence of overweight, but not of obesity, than nondiabetic youth. Future studies of obesity among youth with diabetes of all types will further our understanding of the impact of obesity on diabetes both as a risk factor and a comorbidity.

Neuropsychological profiles of young people with type 1 diabetes 12 yr after disease onset.

Abstract: Lin A, Northam EA, Rankins D, Werther GA, Cameron FJ Neuropsychological profiles of young people with type 1 diabetes 12 yr after disease onset Background: Lowered neuropsychological performance is evident in youth with type 1 diabetes, although evidence for associations with specific illness variables is inconsistent This study examined the neuropsychological profiles of a cohort of youth with type 1 diabetes studied prospectively from diagnosis 12 yr previously Methods: A total of 106 youth with type 1 diabetes and 75 healthy controls participated There were no significant group differences on Full-scale IQ assessed on study entry 12 yr previously, current socioeconomic status, gender distribution, or age Neuropsychological tests assessed eight cognitive domains: verbal abilities, perceptual reasoning, new learning, working memory, non-verbal processing speed, mental efficiency, divided attention, and sustained attention Episodes of serious hypoglycemia and HbA1c levels were recorded from diagnosis Results: Youth with type 1 diabetes performed more poorly than controls on working memory (p < 05) Early onset diabetes was related to poorer sustained (p < 001) and divided attention (p = 001), new learning, and mental efficiency (both p < 05) Hypoglycemia was found to adversely effect verbal abilities, working memory, and non-verbal processing speed (all p < 05) Poorer working memory was associated with hyperglycemia (p < 05) Youth with any combination of two or three illness risk factors (ie, early onset diabetes, hypo-, hyperglycemia), performed more poorly than controls and youth with no or one risk on verbal abilities, working memory, and mental efficiency Conclusions: This study documents poorer neuropsychological performance and its association with illness risk factors in youth with type 1 diabetes Findings suggest that early disease onset and hypoglycemia impact on the developing central nervous system, with hyperglycemia playing a lesser role

Validation of a health administrative data algorithm for assessing the epidemiology of diabetes in Canadian children.

Abstract: Guttmann A, Nakhla M, Henderson M, To T, Daneman D, Cauch-Dudek K, Wang X, Lam K, Hux J. Validation of a health administrative data algorithm for assessing the epidemiology of diabetes in Canadian children. Objective: To validate a case definition of pediatric diabetes using administrative health data and describe trends in incidence and prevalence over time in Ontario, Canada. Methods: We sampled hospital records of 700 children from 1994 to 2003 with a prior history of at least one outpatient or hospital record for diabetes mellitus and 300 randomly selected children with no diabetes records. We defined patients as having diabetes based on diagnoses and drug utilization from chart abstraction and compared sensitivity and specificity of a number of combinations of overall health care use using administrative data to develop a highly specific definition. We used Poisson regression to test changes in incidence over time (1994–2003). Results: Use of four physician claims and no hospital records over a 2-yr period yielded the most specific definition (83% sensitivity, 99% specificity). Using this definition overall age/sex standardized incidence per 100 000 was 32.3 [95% confidence intervals (CI) 30.4, 34.4] and prevalence 241.5 per 100 000 (95% CI 236.2–249.9) in 2003/2004. Overall incidence differs by age, (peaking in 10–14 yr olds) but not significantly by sex. The overall incidence has increased on average by 3.1% per year since 1994 (95% CI 1.02–1.04), with no difference in the rate of increase by age. Conclusions: Population-based surveillance of diabetes in children is possible using administrative data. This will facilitate further study of trends in incidence but also in use of health services and outcomes. Further work to differentiate type 1 and 2 diabetes will be important.

Neurocognitive functioning in preschool-age children with type 1 diabetes mellitus.

Abstract: Neurocognitive functioning may be compromised in children with type 1 diabetes mellitus (T1DM). The factor most consistently implicated in the long-term neurocognitive functioning of children with T1DM is age of onset. The pediatric literature suggests that glycemic extremes may have an effect on the neurocognitive functioning of children, but findings are mixed. The purpose of this study was to compare the neurocognitive functioning of young children with T1DM diagnosed before six years of age and healthy children (i.e., without chronic illness). Additionally, in the children with T1DM, we examined the relationship between their neurocognitive functioning and glycemic control. Sixty eight (36 with T1DM and 32 without chronic illness) preschool-age children (M age = 4.4yrs) were recruited and administered a battery of instruments to measure cognitive, language, and fine motor skills. Children with T1DM performed similarly to the healthy controls and both groups' skills fell in the average range. Among children with diabetes, poor glycemic control (higher HbA1c) was related to lower general cognitive abilities (r = -.44, p < .04), slower fine motor speed (r = -.64, p < .02), and lower receptive language scores (r = -.39, p < .04). Such findings indicate that young children with T1DM already demonstrate some negative neurocognitive effects in association with chronic hyperglycemia.

Oral glucose tolerance testing in children with cystic fibrosis

Abstract: Ode KL, Frohnert B, Laguna T, Phillips J, Holme B, Regelmann W, Thomas W, Moran A. Oral glucose tolerance testing in children with cystic fibrosis. Background: Cystic fibrosis (CF) related diabetes is the most common comorbidity in persons with CF. International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines recommend annual oral glucose tolerance testing (OGTT) screening starting at age 10. The OGTT might be recommended in younger children if, as in adults, it provided clinically relevant prognostic information. A database review was performed to determine whether OGTT findings in children with CF predict subsequent clinical course. Methods: A retrospective matched-pair cohort study was based on OGTTs performed during 1998–2003. Children aged 6–9 were classified as having normal glucose tolerance (NGT) or abnormal glucose tolerance (AGT). Children with AGT were matched by age and gender to those with NGT. Clinical status was assessed at baseline and 5 yr later. In a separate investigation, diabetes and prior AGT status of children aged 10–18 were used to assess predictions derived from the cohort study. Results: In 1998–2003, 39 of 94 children had AGT. Of these, 31 had sufficient follow-up data to be included. Both at baseline and 5 yr later there was no significant difference in height, weight, body mass index (BMI) or lung function between AGT and NGT. Diabetes developed in 13 AGT (42%) and one NGT (3%) [odds ratio (OR) 11, p = 0.0009]. Age of diabetes onset was 12 ± 1 yr in boys and 11 ± 1 yr in girls, compared to approximately 23 yr in the general CF population. Fifteen current children age 10–18 who had AGT before age 10 have diabetes, close to the prediction of 19. Conclusions: AGT in children with CF age 6–9 yr identifies those at high risk for progression to early onset diabetes.

Necrotizing enterocolitis in neonates receiving octreotide for the management of congenital hyperinsulinism.

Abstract: The somatostatin analog octreotide was used for the first time in the treatment of an infant with congenital hyperinsulinism in 1986. Since then, it is commonly used in the management of congenital hyperinsulinemic hypoglycemias. Despite a wide variety of potential adverse reactions, octreotide is generally well tolerated. It has been extensively demonstrated that octreotide reduces the splanchnic blood flow in a dose-dependent manner, affecting the entire gastrointestinal tract, and some concern has been recently raised regarding the potential implications of this effect in the development of necrotizing enterocolitis in neonates receiving octreotide for the management of congenital hyperinsulinism. The aim of this report is to present a series of patients treated at our institution in which we observed this association, and review the current related literature.

Transition from pediatric to adult diabetes care: smooth or slippery?

Abstract: de Beaufort C, Jarosz-Chobot P, Frank M, Frank M, de Bart J, Deja G. Transition from pediatric to adult diabetes care: smooth or slippery? Objectives: The purpose of this study is to evaluate the practices of diabetes health care providers concerning the transition from pediatric to adult diabetes care. The information presented here may help increase awareness of the organization of transitional care for young people with diabetes and prevent the loss of follow-up during this vulnerable period in their lives. Methods: A questionnaire with an explanatory letter was sent to all members (n = 578) of the International Society for Pediatric and Adolescent Diabetes (ISPAD). A follow-up mailing was sent 4 months later. Results: In total, 92 questionnaires (16%) from members representing 36 countries were included in the analysis. In 76% of the centers, youth are seen until the age of 18 yr; 36% of the pediatric centers see adults > 25 yr; 30% report children under the age of 16 receive follow up from adult diabetologists or internists. About half of the programs already have a structured transition process usually targeting youth 16–25 yr of age. The majority of responders propose that preparation for transition starts at least 1 yr prior to leaving the pediatric center. Conclusion: Youth with type 1 diabetes often struggle to keep diabetes management a priority and find it challenging to maintain optimal metabolic control. When they graduate from pediatric care, some of these young people opt out of care altogether, only to resurface in the medical system when they develop complications which may have been prevented. Our survey of diabetes health care professionals in 36 countries worldwide shows that the actual transition practices in many places are far from optimal and require improvement. Transitional care should start early and strategies should promote uninterrupted, comprehensive, and accessible adult care.

Relation of circulating oxidized LDL to obesity and insulin resistance in children

Abstract: Kelly AS, Jacobs DR Jr, Sinaiko AR, Moran A, Steffen LM, Steinberger J. Relation of circulating oxidized LDL to obesity and insulin resistance in children. Introduction: Circulating oxidized low-density lipoprotein (LDL), a marker of oxidative stress, is associated with obesity, insulin resistance, metabolic syndrome, and cardiovascular disease in adults. However, little is known about its relation to insulin resistance and cardiovascular risk factors in children. The purpose of this study was to assess the relation of oxidative stress, measured by circulating oxidized LDL, with measures of adiposity and insulin resistance in children. Methods: Oxidized LDL, measures of body fatness (body mass index: BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral and subcutaneous fat), insulin resistance with euglycemic insulin clamp (Mlbm), blood pressure, and blood lipids were obtained in 78 children. Oxidized LDL was compared between normal weight children (BMI < 85th percentile) and overweight/obese children (BMI ≥ 85th percentile) and levels were evaluated for associations with body fatness and insulin resistance. Results: Oxidized LDL levels were significantly higher in overweight/obese vs. normal weight children (p < 0.0001). Oxidized LDL was significantly correlated with BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral fat, and abdominal subcutaneous fat (all p-values <0.0001). Moreover, oxidized LDL was negatively correlated with Mlbm, even after adjustment for adiposity (p < 0.01). Conclusions: Oxidized LDL is significantly associated with adiposity and with insulin resistance, independent of body fatness, in children. Oxidative stress may be independently related to the development of insulin resistance early in life, especially in obese youth.

Wolfram syndrome: important implications for pediatricians and pediatric endocrinologists

Abstract: Kumar S. Wolfram syndrome: important implications for pediatricians and pediatric endocrinologists.

Characterization of 33 488 children and adolescents with type 1 diabetes based on the gender-specific increase of cardiovascular risk factors.

Abstract: Schwab KO, Doerfer J, Marg W, Schober E, Holl RW. Characterization of 33 488 children and adolescents with type 1 diabetes based on the gender-specific increase of cardiovascular risk factors. Objectives: Characterization of children with type 1 diabetes (T1DM) regarding number and gender distribution of cardiovascular risk factors (cvRF) and of total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C ratio) for risk assessment. Methods: 33488 patients ≤18 years were included in this cross-sectional analysis and placed into 5 categories by their number of cvRF. Dyslipidemia (TC >200 mg/dL, >5.17 mmol/L; and/or HDL-C 130 mg/dL, >3.36 mmol/L), elevated systolic and/or diastolic blood pressure (BP) ≥90th percentile, obesity >97th percentile, active smoking, and HbA1c ≥7.5% were considered as cvRF. Results: 65% had no or 1 cvRF. HbA1c ≥7.5% was the most frequently occurring cvRF followed by BP ≥90th percentile, dyslipidemia, smoking, and BMI >97th percentile. Age at diabetic onset ranged from 7.7 to 9.2 years and diabetes duration from 4.1 to 6.6 years. CvRF showed differences in disfavour of females except smoking and HDL-C <35 mg/dL (0.91 mmol/L). Rate of females was 45% with 0 cvRF and 60% with 4 to 5 cvRF. TC/HDL-C ratio showed no clear association to the number of cvRF. Conclusions: 35% of a pediatric T1DM population develops 2 or more cvRF thus increasing their cv risk in adulthood. With increasing numbers of cvRF, the percentage of girls is rising from 45% to 60% which might contribute to an assimilation of survival rates in female and male adults. TC/HDL ratio does not predict the extent of cardiovascular risk in pediatric T1DM.

Discontinuation of insulin pump treatment in children, adolescents, and young adults. A multicenter analysis based on the DPV database in Germany and Austria

Abstract: Hofer SE, Heidtmann B, Raile K, Frohlich-Reiterer E, Lilienthal E, Berghaeuser MA, Holl RW for the DPV-Science-Initiative and the German working group for insulin pump treatment in pediatric patients. Discontinuation of insulin pump treatment in children, adolescents, and young adults. A multicenter analysis based on the DPV database in Germany and Austria. Background: Insulin pump therapy is well established in the treatment of children and adolescents with type 1 diabetes. Most studies focus on outcome parameters like hemoglobin A1c (HbA1c), hypoglycemia, and quality of life, whereas few reports address patients who discontinue pump therapy. Objective: This survey focuses on the discontinuation rate of insulin pump treatment in the pediatric and young adult age group. Subjects and methods: The prospective multicenter Diabetes Patienten Verlausdokumentation (DPV) (electronic diabetes patient documentation system) database has been established since 1990 and is broadly used in Germany and Austria. All pump users among the participating centers documented since 1995 were included in this analysis. Results: In total, 11 710 patients with type 1 diabetes were recorded as treated with insulin pumps. In total, 463 patients (4%) switched from insulin pump treatment to multiple daily injections (MDI). In the group of patients who stopped with pump treatment, the mean duration of pump therapy was 1.7 yr (SE ± 0.06 yr), 60.5% of patients were female. Subdivided into age groups, the discontinuation rate was lowest in the age group < 5 yr (0.1%), followed by the groups aged 5–10 yr (0.3%) and 15–20 yr (0.8%). The group aged 10–15 yr showed the highest rate of discontinuation (2%). Conclusions: The discontinuation rate of insulin pump therapy is, in general, low (4%). The younger the patients at the time of initiating insulin pump treatment, the lower is the discontinuation rate. The highest rate was seen in adolescents aged 10–15 yr. Girls stopped insulin pump treatment more often than boys (60.5% vs. 39.5%).

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

Abstract: 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.

Correlates of glycemic control and quality of life outcomes in adolescents with type 1 diabetes

Abstract: Ingerski LM, Laffel L, Drotar D, Repaske D, Hood KK. Correlates of glycemic control and quality of life outcomes in adolescents with type 1 diabetes. Background: A major focus of pediatric multidisciplinary diabetes care is promoting glycemic control (A1c) while ensuring high quality of life (QOL). The current study investigated factors associated with A1c and QOL using a methodology that considered these variables as simultaneous outcomes. Method: A total of 261 adolescents (aged 13–18) with type 1 diabetes completed measures of blood glucose monitoring (BGM) frequency, diabetes-specific QOL, negative affect, and depression. Caregivers completed measures of demographic and disease characteristics, depression, and family conflict. Results: A1c was negatively correlated with QOL (r = −0.18 to −0.29, p < 0.01) across all subscales. Based on clinical A1c goals and median QOL scores, adolescents fell into four glycemic control–QOL groups. Multinomial logistic regression determined correlates of group membership utilizing adolescents with suboptimal glycemic control–low QOL as the referent group. Adolescents with optimal glycemic control–high QOL reported increased BGM frequency (OR = 1.87), less negative affect (OR = 1.32), and were more likely to use CSII (OR = 5.41). Adolescents with optimal A1c–low QOL reported greater BGM frequency (OR = 1.91) and shorter disease duration (OR = 1.09). Adolescents with suboptimal glycemic control–high QOL reported greater BGM frequency (OR = 1.41), fewer depressive symptoms (OR = 1.13), and less negative affect (OR = 1.31). Conclusions: Results reveal disease, management, and psychosocial characteristics that differentiate glycemic control–QOL outcome groups and identify risk factors related to this relationship. Further appreciation of these characteristics may increase clinicians' understanding and attention to these important clinical outcomes and help tailor the most appropriate interventions (e.g., individual psychotherapy vs. family problem-solving interventions) to help adolescents achieve glycemic control without sacrificing QOL.

Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies.

Abstract: Delli AJ, Lindblad B, Carlsson A, Forsander G, Ivarsson S-A, Ludvigsson J, Marcus C, Lernmark A; for the Better Diabetes Diagnosis (BDD) Study Group. Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies. Aim: To determine whether type 1 diabetes mellitus (T1DM) patients, having parents who immigrated to Sweden, have increased T1DM risk before 18 yr compared with countries of origin. We also determined whether they have different human leukocyte antigen (HLA) genetic markers and islet autoantibodies at diagnosis compared with Swedish patients. Methods: A total of 1988 (53% males) newly diagnosed and confirmed T1DM patients /=2) autoantibodies (p < 0.04) and specifically IA-2Ab (p < 0.001) were most prevalent among the Swedish patients. Multiple autoantibodies were associated with DQ8 among the Swedish patients only (p < 0.001). Conclusion: Patients born to parents who had immigrated to the high T1DM incidence environment of Sweden have, compared with Swedish patients, more frequent HLA-DQ2 genetic markers and are diagnosed more often with GAD65Ab. (Less)

Hemoglobin glycation index: a robust measure of hemoglobin A1c bias in pediatric type 1 diabetes patients.

Abstract: Soros AA, Chalew SA, McCarter RJ, Shepard R, Hempe JM. Hemoglobin glycation index: a robust measure of hemoglobin A1c bias in pediatric type 1 diabetes patients. Background: The hemoglobin glycation index (HGI) assesses biological variation in A1c after accounting for the effect of mean blood glucose (MBG). Previous studies minimized analytical variation that could mask biological variation and showed that HGI was consistent within individuals over time and positively associated with risk for microvascular complications. We tested the hypothesis that biological variation in A1c can be assessed by HGI calculated using routine MBG and A1c data obtained from a typical diabetes clinic. Methods: Self-monitored MBG and A1c were collected from charts of 202 pediatric type 1 diabetes patients attending 1612 clinic visits over 6 yr. Predicted A1c was calculated from the linear regression equation of A1c on MBG in the study population. HGI was calculated by subtracting predicted A1c from observed A1c. Patients were divided into low, moderate, and high HGI tertile groups. Results: Patients used 12 models of glucose meters. Download protocols varied with clinical practice over time. A1c was measured by multiple assays and laboratories. Despite this analytical heterogeneity, HGI was significantly different between individuals and correlated within individuals. MBG (mean ± SD, mg/dL) was similar in the low (186 ± 31), moderate (195 ± 28), and high (199 ± 42) HGI groups. A1c (%) was significantly different (p < 0.0001) in the low (7.6 ± 0.7), moderate (8.4 ± 0.7), and high (9.6 ± 1.1) HGI groups. Conclusion: Biological variation in A1c is a robust quantitative trait that can be assessed using HGI calculated from routine clinic data. This suggests that HGI could be used clinically for more personalized assessment of complications risk.

The establishment of a new national network leads to quality improvement in childhood diabetes: Implementation of the ISPAD Guidelines

Abstract: Aims To investigate whether implementation of International Society for Pediatric and Adolescent Diabetes (ISPAD) Guidelines and the establishment of a system for nationwide anonymous comparison, between treatment centres, of quality indicators for childhood diabetes could lead to improvement in diabetes care. Methods Children and adolescents with type-1 diabetes in Norway are treated at the public hospitals. Data were collected prospectively yearly according to standardized written instructions. Quality indicators were defined and benchmarked. HbA1c was measured at a central national Diabetes Control and Complications Trial (DCCT) standardized laboratory. Results The participation increased with 454 type-1 diabetes patients from eight clinics included in 2001 and 1658 patients from 25 clinics in 2005. The adherence rate in 2005 was 85% of all eligible patients from 25 of 26 pediatric clinics. The mean HbA1c of all clinics improved (8.6% in 2001 and 8.1% in 2005) and this was statistically significant (p Conclusions During the establishment of a system for benchmarking of diabetes treatment in Norway the outcomes showed significant improvements associated with changes in management and the quality of screening assessments. Benchmarking combined with organized quality meetings and discussions was effective to improve outcome on a national level.

Incidence of neonatal diabetes in Austria-calculation based on the Austrian Diabetes Register.

Abstract: Background: Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes which is diagnosed in the first 6 months of life. Several studies in the last few years provide information on genetic causes for NDM. Objective: The aim of this study was to identify all patients with diabetes in the first 6 months of life through the Austrian Diabetes Register, which is available since 1989. A retrospective data analyses was performed to calculate the current incidence of NDM. Subjects and Methods: Ten patients were registered with diabetes onset within the first 6 months of life in the Austrian Diabetes Register. Evaluation of detailed clinical data was performed by sending a questionnaire to all diabetes centers. Results: Ten patients from nine different families with NDM were diagnosed in Austria from 1989 until September 2007. Seven patients (one male, six females) had transient NDM (TNDM), three (two males, one female) showed a permanent course [permanent neonatal diabetes mellitus (PNDM)]. One had immunodeficiency, polyendocrinopathy and enteropathy X-linked (IPEX) syndrome and another showed aplasia of the pancreas; no genetic etiology was found in the third case. In three out of seven patients with a transient course of NDM a genetic diagnosis was possible. Two female siblings had activating point mutations in the ABCC8 gene, although one patient had paternal uniparental isodisomy of chromosome 6q24. One patient's family did not consent to genetic testing. Conclusions: The incidence of NDM in Austria is 1/160 949, with an incidence of 1/ 536 499 for PNDM and 1/229 928 for TNDM.

Psychological symptoms and insulin sensitivity in adolescents.

Abstract: Low insulin sensitivity is a major physiological precursor to type 2 diabetes and an important risk factor for the development of cardiovascular disease [1]. One of the primary pathways by which decreased insulin sensitivity develops is through excessive gain of body fat. Overweight youth have decreased insulin sensitivity compared to their non-overweight counterparts, placing them at heightened risk for negative health consequences including type 2 diabetes [2]. However, evidence from adult studies suggests that psychological factors may also affect insulin sensitivity [3–11]. In overweight and non-overweight adults, sub-clinical and clinical threshold depressive symptoms are correlates of, and potential risk factors for, the development of decreased insulin sensitivity [3, 6–10], type 2 diabetes [5, 12, 13], and other aspects of the metabolic syndrome [4, 11]. The degree of psychosocial stress and anxiety symptoms in a large community sample of women also has been shown to be significantly related to measures of insulin sensitivity, even after accounting for body mass index [4]. From a psychophysiological theoretical perspective, depression or anxiety are believed to impact insulin sensitivity through physiological mechanisms such as altered insulin signaling in the brain, pro-inflammatory activation, and/or distress-induced upregulation of counterregulatory hormone systems [14, 15]. In addition, from a behavioral psychology perspective, depression and stress may affect insulin sensitivity, in theory, through their impact on lifestyle factors such as physical inactivity. Given the possible role that adult studies suggest for depression and anxiety in the development of decreased insulin sensitivity, understanding how these factors are linked to glucose homeostasis during adolescence may be important for identifying early risks for potentially adverse health outcomes. Parents’ perceptions of their children’s negative emotionality have been found to be associated with children’s fasting insulin, particularly among boys, in a large study of Finnish youth ages 6 to 18 years [16]. To our knowledge, however, no studies to date have examined the links between depressive or anxiety symptoms and fasting insulin or measures of insulin sensitivity in youth. Adolescence represents an important developmental stage for understanding the links between psychological symptoms and insulin sensitivity. During adolescence, normative endocrine changes associated with puberty produce decreased insulin sensitivity relative to childhood. Moreover, adolescence marks a peak time for the onset of depressive symptoms, particularly among girls. Thus, these marked psychological and biological shifts render adolescence an important developmental stage for understanding how symptoms of depression are associated with insulin sensitivity. We, therefore, investigated whether symptoms of depression and anxiety were associated with insulin sensitivity among adolescents. Based upon prior data, we hypothesized that symptoms of depression and anxiety would be associated with higher fasting insulin and decreased insulin sensitivity. Since previous literature has indicated that sex may act as a moderator of the association between psychological symptoms and insulin sensitivity [9, 16], we expected that sex might interact with depression or anxiety and their association with insulin measures, such that the effects would be stronger for girls than for boys.

Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations.

Abstract: Pruhova S, Dusatkova P, Sumnik Z, Kolouskova S, Pedersen O, Hansen T, Cinek O, Lebl J. Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations. Background: Glucokinase diabetes, also called GCK-MODY or maturity-onset diabetes of the young type 2 (MODY2), is caused by heterozygous mutations in the gene encoding glucokinase (GCK). Objective: The aim of study was to investigate the current prevalence of GCK mutations in a large cohort of Czech patients with typical clinical appearance of GCK-MODY. In addition, we reanalyzed the negative results obtained previously by screening using the denaturing high-performance liquid chromatography (dHPLC). Methods: We studied 140 unrelated Czech probands with clinical picture of GCK-MODY who were referred to our center from the whole of the Czech Republic between the years 1999–2009 by direct sequencing of GCK gene. Results: A mutation in GCK was identified in 103 of 140 probands (74%). We identified 46 different GCK mutations of which 13 were novel. Several mutations were detected in multiple families: p.Glu40Lys (20 families), p.Gly318Arg (12), p.Leu315His (7) and p.Val33Ala (six families). Direct sequencing detected a GCK mutations in 9 of 20 previously dHPLC-negative samples; the sensitivity of the dHPLC screening was calculated as 84%. Conclusions: The study shows a relatively high proportion of GCK mutations among individuals with GCK-like phenotype, confirming the effectiveness of carefully applied clinical criteria prior to genetic testing. In the Czech MODY registry, GCK-MODY represents the biggest subgroup of MODY (35%). We report several prevalent GCK mutations with a likely founder effect in the Czech population. Furthermore, our results provide ground for a possible recommendation to reinspect all negative results previously obtained by screening using dHPLC.

Low dose (0.05 units/kg/h) is comparable with standard dose (0.1 units/kg/h) intravenous insulin infusion for the initial treatment of diabetic ketoacidosis in children with type 1 diabetes—an observational study

Abstract: Puttha R, Cooke D, Subbarayan A, Odeka E, Ariyawansa I, Bone M, Doughty I, Patel L, Amin R. Low dose (0.05 units/kg/h) is comparable with standard dose (0.1 units/kg/h) intravenous insulin infusion for the initial treatment of diabetic ketoacidosis in children with type 1 diabetes—an observational study Objective: To compare low dose (0.05 units/kg/h) with standard dose (0.1 units/kg/h) intravenous insulin infusion for the treatment of diabetic ketoacidosis (DKA) in children with type 1 diabetes. Study design: Data from five paediatric centres were compared in children who received 0.05 (41 episodes) or 0.1 units/kg/h (52 episodes). Results: In the low vs. standard dose group, at 6 h following admission, the fall in blood glucose levels [11.3 (95% confidence interval 8.6 to 13.9) vs. 11.8 (8.4 to 15.2) mmol/L, p = 0.86] and rise in pH [0.13 (0.09 to 0.18) vs. 0.11 (0.07 to 0.15), p = 0.78] were similar. These changes were comparable between doses in relation to: severity of initial acidosis, children newly diagnosed with diabetes or aged less than 5 years. After adjustment for other clinical and biochemical covariates, insulin dose was unrelated to the change in pH and blood glucose levels at 6 h following admission. Comparisons of safety data, particularly in relation to abnormal Glasgow Coma Score, were inconclusive. Conclusion: In this observational study, low dose was as effective as standard dose intravenous insulin infusion in the initial treatment (less than 6 h) of DKA in children with type 1 diabetes. A randomised controlled trial is required to show true equivalence between doses and to evaluate potential safety benefits.

A 5-yr follow-up nerve conduction study for the detection of subclinical diabetic neuropathy in children with newly diagnosed insulin-dependent diabetes mellitus

Abstract: Lee S-S, Han H-H, Kim H. A 5-yr follow-up nerve conduction study for the detection of subclinical diabetic neuropathy in children with newly diagnosed insulin-dependent diabetes mellitus. Pediatric Diabetes 20XX: 00: 000–000 Objective: To investigate the changes of peripheral nerve conduction in children with insulin-dependent diabetes mellitus (IDDM) prospectively from diagnosis and to know how those results were related to clinical risk factors. Methods: A total of 37 patients (14 males and 23 females) aged 3–19 yr (mean 12.0 ± 3.7) with newly diagnosed IDDM underwent bilateral nerve conduction studies (NCS) of median, ulnar, posterior tibial, peroneal, and sural nerves annually for 5 yr. Results: In all, 12 patients (32.4%) showed electrophysiological evidence of polyneuropathy in at least two different nerves including the sural nerve at the diagnosis of IDDM; 20 patients (54%) had multiple (≥2) abnormalities in parameters of NCS. The most common abnormal parameters at the diagnosis were conduction velocities of peroneal motor and sural nerves. In sequential NCS over 5 yr, the percentage of abnormal nerve conduction velocities rose except within the sural nerve. Poor metabolic control, height, duration of diabetes, and older age of onset were related to the changes of parameters of NCS over 5 yr. Among those risk factors, the duration of diabetes and sustained hyperglycemia affected the parameters of NCS more frequently than others. Conclusions: Children with IDDM frequently have nerve conduction abnormalities without clinical neuropathy at initial diagnosis. The frequency of abnormalities of any attribute of nerve conduction increased over the 5 yr follow-up. The duration of diabetes and poor glycemic control proved to be more important risk factors over 5 yr as related to the development of subclinical neuropathy.

Wolcott–Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature*

Abstract: Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by an early-infancy-onset diabetes mellitus associated with a variety of multisystemic clinical manifestations. Here, we present six patients with WRS, carrying the same homozygous mutation (EIF2AK3-W522X), from two unrelated Turkish families. This is the largest series of patients with the same mutation for this rare syndrome. In this communication we compare clinical features of these six patients with the other 34 patients who have been reported to date, and review the clinical features of WRS. All WRS patients presented first with symptoms of insulin dependent diabetes mellitus, with a mean age at onset of 2 months. All patients had skeletal dysplasia or early signs of it, and growth retardation. Many of the patients with WRS have been reported to have developmental delay, mental retardation, and learning difficulties; in contrast, none of our patients showed abnormal development at age up to 30 months. Acute attacks of hepatic failure were reported in 23 cases out of 37 patients; in 15 of those 23 cases an acute attack of renal failure accompanied the liver failure. Exocrine pancreatic deficiency has been reported in only four cases other than our four patients. Central hypothyroidism was observed in six of 28 cases. We propose that central hypothyroidism is not a component of WRS, but rather a reflection of euthyroid sick syndrome. Four of our patients experienced severe neutropenia, compared to only five of the 27 other cases, suggesting that the W522X mutation may be specifically associated with neutropenia. Other than the consistent features of diabetes mellitus and epiphyseal dysplasia, WRS patients are otherwise characterized by extensive phenotypic variability that correlates poorly to genotype.

Increasing incidence of childhood-onset type 1 diabetes mellitus among Estonian children in 1999-2006. Time trend analysis 1983-2006.

Abstract: Teeaar T, Liivak N, Heilman K, Kool P, Sor R, Paal M, Einberg U, Tillmann V. Increasing incidence of childhood-onset type 1 diabetes mellitus among Estonian children in 1999–2006. Time trend analysis 1983–2006. Background: The incidence of childhood-onset type 1 diabetes mellitus (T1DM) among Estonian children under 15 years of age was 10.1 per 100 000 per year in 1983–1990 and 12.2 per 100 000 per year in 1991–1998 with the highest incidence in age-group 10.0–14.9 years in both periods. From 1983 to 1998, the incidence increased most rapidly in age-group 0–4.9 years. Objective: To determine the incidence of T1DM among Estonian children in 1999–2006 and to compare the results with the data from 1983 to1998. Subjects and methods: In 1999–2006, population-based incidence data were collected from two centers where all children with T1DM are seen after the diagnosis. Data for earlier periods were obtained from previously published data. Subjects were divided into three age-groups: 0–4.9 years, 5.0–9.9 years and 10.0–14.9 years. Results: Between 1999 and 2006, 310 new cases of T1DM were diagnosed in Estonian children aged 0–14.9 years. The age-standardized incidence rate for that period was 17.2 [95% confidence interval (CI) 13.1–21.2]. The incidence was the highest, 21.2 (95% CI 17.7–25.3) in age-group 5.0–9.9 years. Over the time period 1983–2006, the incidence of childhood-onset T1DM in Estonian children under 15 years of age increased annually by an average 3.3% with the most rapid annual increase–9.3%–occurring in the youngest age-group. Conclusions: The incidence of childhood-onset T1DM in Estonia continues to rise and the age of onset of the disease becomes younger.

Adolescents on basal-bolus insulin can fast during Ramadan.

Abstract: Al-Khawari M, Al-Ruwayeh A, Al-Doub K, Allgrove J. Adolescents on basal-bolus insulin can fast during Ramadan. Fasting during Ramadan is a major tenet of the Muslim religion. All adults after the age of puberty are required to do so if health permits. However, there are exemptions to this requirement and having a chronic condition such as diabetes is one. Nevertheless, many adults and adolescents feel obliged to fast during Ramadan even though there is no absolute need to do so. This obligation must be respected. There are few data to support this practice in those whose condition, such as diabetes, potentially makes them vulnerable to developing problems during prolonged fasting. This study was designed to examine the ability and safety of young people with diabetes to be able to fast if they so desire. Two groups of patients were studied, those on a multiple injection, so-called basal-bolus, regimen and those on a ‘conventional’ twice daily pre-mixed insulin regimen. All patients showed a tendency to high blood glucose at the time of commencing their fast. Those on twice daily insulin continued to have hyperglycaemia during the day whilst those on basal-bolus insulin showed a steady fall in blood glucose towards normal by the time of breaking their fast. Although there was a greater tendency to hypoglycaemia in the basal-bolus group, this could be successfully prevented by reducing the dose of basal insulin by 10–20%. We recommend that it is safe for adolescents with diabetes to fast during Ramadan as long as they reduce their basal insulin by this amount and continue to monitor their blood glucose regularly.

Autonomy and insulin in adolescents with type 1 diabetes

Abstract: Research concerning adolescent development and diabetes that considers the impact of various new treatment modalities has valuable implications for the development of appropriate education and intervention strategies for this population. The recommendation for intensive insulin therapy in type 1 diabetes (T1D) in adolescence has resulted in a number of studies demonstrating the medical benefits of the various modalities of such treatment (1–3). However, fewer studies explore the psychosocial impact of this intensive therapy on adolescents and families (4). In this article, we examine the research on autonomy in adolescents with T1D and consider the ‘pump vs. injections’ debate from a developmental perspective. The final section of this article includes general recommendations and pump-specific considerations for diabetes health-care providers to encourage safe autonomy development in adolescents with T1D. T1D is a genetic disease of the immune system characterized by pancreatic beta cell destruction and a consequent lack of insulin. Recent data suggest that 15 000 youth in the USA are diagnosed with T1D each year, and the incidence rate is highest in children aged 10–14 (5). The recommendations by the American Diabetes Association (ADA) support the use of an intensive insulin regimen that involves a ‘basal/bolus’ pattern of insulin administration to maintain blood glucose levels as close to normal as possible, with a target hemoglobin A1c (HbA1c) of less than 7.5% for adolescents (aged 13–19) (6). This pattern can be achieved by either multiple daily injections (MDI), which involve a daily injection of a long-acting (basal) insulin and injections of rapid-acting (bolus) insulin to cover meals and to correct high-blood sugars, or continuous subcutaneous insulin infusion (CSII), in which basal insulin is delivered by the constant infusion of small amounts of rapid-acting insulin through an insulin pump (6–8). Both types of basal/bolus therapy require frequent blood glucose monitoring (at least four/day) and tracking carbohydrate intake and exercise in order to make insulin dosing decisions (9). The ADA also emphasizes the need for developmentally appropriate interventions that include adolescents and their caregivers (6).

Hyperbaric oxygen therapy improves early posttransplant islet function

Abstract: Sakata N, Chan NK, Ostrowski RP, Chrisler J, Hayes P, Kim S, Obenaus A, Zhang JH, Hathout E. Hyperbaric oxygen therapy improves early posttransplant islet function. Objective: This study investigates the therapeutic potential of hyperbaric oxygen therapy (HBO) in reducing hypoxia and improving engraftment of intraportal islet transplants by promoting angiogenesis. Methods: Diabetic BALB/c mice were transplanted with 500 syngeneic islets intraportally and received six consecutive twice-daily HBO treatments (n = 9; 100% oxygen for 1 h at 2.5 atmospheres absolute) after transplantation. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) was used to assess new vessel formation at postoperative days (POD) 3, 7, and 14. Liver tissue was recovered at the same time points for correlative histology, including: hematoxylin and eosin, hypoxia-inducible factor (HIF1α), Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), vascular endothelial growth factor (VEGF), and von Willebrand Factor immunohistochemistry. Results: HBO therapy significantly reduced HIF-1α, TUNEL and VEGF expression in islets at POD 7. In the non-HBO transplants, liver enhancement on DCE MRI peaked at POD 7 consistent with less mature vasculature but this enhancement was suppressed at POD 7 in the HBO-treated group. The number of new peri-islet vessels at POD 7 was not significantly different between HBO and control groups. Conclusion: These results are consistent with a hyperbaric oxygen-mediated decrease in hypoxia that appeared to enhance vessel maturation in the critical days following intraportal islet transplantation.

Successful treatment of severe subcutaneous insulin resistance with inhaled insulin therapy.

Abstract: The potential of inhaled insulin therapy for severe resistance to subcutaneous insulin was tested in a 7-yr old boy with type 1 diabetes mellitus. The efficiency of 1 mg inhaled insulin (Exubera) was examined by a 4-h euglycemic clamp study. During the clamp, the glucose infusion rate started to increase 25 min after inhalation and peaked 120 min after inhalation. Subsequently, a trial of inhaled insulin monotherapy was initiated consisting of pre-meal inhalations and one inhalation during the night. Since glycemic control remained fair (HbA1c approximately 8.5%), this therapy was continued. Over the ensuing 18 months, mild keto-acidosis occurred twice during gastro-enteritis. Inhaled insulin was well tolerated and pulmonary function did not deteriorate. We conclude that severe resistance to subcutaneous insulin does not preclude sufficient absorption of insulin delivered by pulmonary.

Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1 diabetes mellitus

Abstract: El-Karaksy HM, Anwar G, Esmat G, Mansour S, Sabry M, Helmy H, El-Hennawy A, Fouad H. Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1 diabetes mellitus. Background and aim: Children with type 1 diabetes mellitus (T1DM) are frequently investigated for hepatic abnormalities. This study was carried out to report on the prevalence of hepatic abnormalities in diabetic children and adolescents and to highlight the possible etiology and appropriate management. Methods: The study included 692 children (333 were males) with T1DM attending the Diabetes Unit at Cairo University Pediatric Hospital. Their mean age was 9.65 ± 4.18 yr. All children were subjected to clinical examination for hepatomegaly, determination of alanine aminotransferase (ALT) and antibodies to hepatitis C virus (anti-HCV), and abdominal ultrasonography. All children with clinical, laboratory or ultrasound abnormality were counseled about proper glycemic control and followed up. If abnormalities persisted, more detailed investigations were carried out. HCV RNA was done for anti-HCV positive children. Results: Sixty (8.7%) were found to have one or more abnormalities: clinical hepatomegaly in 13 (1.9%), elevated ALT in 27 (3.9%), anti-HCV in 25 (3.6%) and abnormal hepatic ultrasound in 31 (4.5%). Forty percent of anti-HCV positive children were HCV-RNA positive. Glycogenic hepatopathy was diagnosed in three cases by liver biopsy. Abnormalities were reversible in 37/60 after proper glycemic control. Conclusion: Although diabetic children are at risk of acquisition of HCV, poor glycemic control is the key factor that predisposes to hepatomegaly, elevated ALT and abnormal ultrasound findings. A 4 to 8-wk therapeutic trial of proper glycemic control is recommended prior to more invasive diagnostic procedures.

Hypoglycaemia in childhood onset type 1 diabetes--part villain, but not the only one.

Abstract: Northam EA, Lin A. Hypoglycaemia in childhood onset type 1 diabetes –part villain, but not the only one.

Increased arterial stiffness in children and adolescents with type 1 diabetes: no association between arterial stiffness and serum levels of adiponectin.

Abstract: Galler A, Heitmann A, Siekmeyer W, Gelbrich G, Kapellen T, Kratzsch J, Kiess W. Increased arterial stiffness in children and adolescents with type 1 diabetes: no association between arterial stiffness and serum levels of adiponectin. Objective: Type 1 diabetes is associated with an increased risk of atherosclerosis. Adiponectin serum levels correlate inversely with cardiovascular disease in adults. The aim of this study was to examine associations between arterial stiffness indices and serum adiponectin concentrations in children and adolescents with type 1 diabetes and to study the impact of metabolic control. Subjects and methods: We evaluated arterial stiffness, distensibility, and compliance in 93 children and adolescents with type 1 diabetes and correlated the data with clinical parameters and HbA1c levels. The control group comprised 85 matched healthy children. Serum levels of adiponectin in children with diabetes were measured by enzyme-linked immunoassay and correlated with arterial stiffness indices. Results: Arterial stiffness was significantly increased in children and adolescents with type 1 diabetes (aged 13.0 ± 3.8 yr) compared with matched healthy children (p = 0.03). Arterial stiffness was elevated in males with type 1 diabetes compared with females (p = 0.023). Arterial distensibility was significantly lower in children with diabetes compared with healthy controls (p = 0.025). Arterial stiffness, distensibility, and compliance did not correlate with diabetes duration, level of HbA1c, or serum cholesterol. Adiponectin concentrations in children and adolescents with diabetes were significantly elevated compared with normal values based on gender, age, and body mass index. We found no significant associations between arterial stiffness indices and adiponectin levels in children with type 1 diabetes. Conclusions: Children and adolescents with type 1 diabetes had increased arterial stiffness and reduced arterial distensibility and arterial compliance. However, no associations between arterial functional alterations and adiponectin concentrations were seen.