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OBJECTIVE--The risk of cardiovascular death before the age of 40 is 20-fold higher in patients with type 1 diabetes mellitus (T1DM). Endothelial progenitor cells (EPCs) predict cardiovascular morbidity and mortality [...]

OBJECTIVE--Down syndrome (DS) is associated with an increased risk of diabetes, particularly in young children. HLA-mediated risk is however decreased in children with DS and diabetes (DSD). We hypothesized that [...]

OBJECTIVE--To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN [...]

Short interbirth interval has been associated with maternal complications and childhood autism and leukemia, possibly due to deficiencies in maternal micronutrients at conception or increased exposure to sibling infections. A possible association between interbirth interval and subsequent risk of childhood type 1 diabetes has not been investigated. A secondary analysis of 14 published observational studies of perinatal risk factors for type 1 diabetes was conducted. Risk estimates of diabetes by category of interbirth interval were calculated for each study. Random effects models were used to calculate pooled odds ratios (ORs) and investigate heterogeneity between studies. Overall, 2,787 children with type 1 diabetes were included. There was a reduction in the risk of childhood type 1 diabetes in children born to mothers after interbirth intervals, Childhood type 1 diabetes is caused by the autoimmune destruction of the pancreatic [beta]-cells. The marked increases in incidence in recent decades (1) suggest a role for environmental exposures. Researchers [...]

OBJECTIVE--To describe the diabetes phenotype in Wolfram syndrome compared with type 1 diabetes, to investigate the effect of glycemic control on the neurodegenerative process, and to assess the genotype-phenotype correlation. [...]

OBJECTIVE--The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. RESEARCH DESIGN AND METHODS--Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. RESULTS--Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity [I.sup.2] = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS--There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age. Diabetes 59:486-494, 2010, In recent decades, the age at which women give birth has been increasing in many western countries. For instance, between 1987 and 2007, the age of mothers at delivery increased [...]

OBJECTIVE--The aim of this study was to compare the glycemic control of preprandial versus postprandial injections of the new rapid-acting insulin analogue aspart in children and adolescents with type 1 [...]

OBJECTIVE--Arterial blood pressure was followed in 868 patients with type 1 diabetes aged 6.0-19.9 years in 95 centers in Germany and Austria. RESEARCH DESIGN AND METHODS-- European blood pressure reference [...]

To assess the influence of gluten-free diet (GFD) compliance on the quality of life (QOL) of adolescents with coeliac disease (CD), and the impact of patient's age at time of diagnosis. Participants included 365 subjects: 283 adolescents (10–20 years old) with biopsy-proven CD and 82 adolescents without a chronic condition matched for age, sex, education, and social status. Their subjective QOL—comprising physical, mental, and social dimensions as defined by the World Health Organization—was measured and has been analyzed according to compliance status and age at CD diagnosis. Adolescents noncompliant with GFD reported a lower general QOL, more physical problems, a higher burden of illness, more family problems, and more problems in leisure time than adolescents who are compliant with GFD. More frequent GFD transgressions were associated with poorer QOL. Higher problem anticipation and higher feelings of “ill-being” were found in the noncompliant group. No differences between compliant patients with CD and adolescents without any chronic condition were found in all QOL aspects. Adolescents with a late CD diagnosis showed more problems at school and in social contact with peers, as well as worse physical health and higher CD-associated burden. Compliance with GFD is an essential factor to obtain optimal QOL. Psychosocial and educational support should be provided for patients having difficulties strictly adhering to GFD. Early CD onset and diagnosis is associated with better physical health, lower CD-associated burden and fewer social problems, indicating the importance of the earliest CD diagnosis possible.

Aim: To assess the neurological and clinical long-term outcome of patients diagnosed with congenital hyperinsulinism (CHI) in Austria. Patients and Methods: Fourteen patients diagnosed with CHI (1978-2000) were investigated retrospectively by reviewing hospital records. Thirteen of them were evaluated with either a questionnaire or clinical, neurological and biochemical investigations (age at evaluation 4.2- 25.5 years) in a follow-up study in the year 2004. Results: Fifty percent of the patients needed a pancreatectomy. The prevalence of mental retardation was 31%, of epilepsy 15% and of pancreatic insufficiency 14%. None of our patients had developed diabetes mellitus. Additionally the prevalence of obesity was 43% in patients after pancreatectomy. Sixty-nine percent of the patients had no further treatment at the time of follow-up. Conclusion: Despite early diagnosis and intensive treatment, 31% of the patients presented with mental retardation.

AbstractBackground/Aims:To study the 2-year course of children and adolescents with type 2 diabetes mellitus (T2DM) in general practice to present (1) the treatment modalities, (2) patient adherence, and (3) the occurrence of comorbidities. Methods:HBA1c, lipids, blood pressure, treatment modalities, occurrence of retinopathy and nephropathy were analyzed in 129 children and adolescents with T2DM (median age 13.4 years, 75 female) in specialized diabetes centers in Germany. Results:Seventy-eight (60) children dropped out of care after a mean of 7.1 months. Drug treatment was not stopped in any of the 64 children initially treated with antidiabetic drugs. Sixteen (12) children were treated solely by lifestyle intervention over the 2-year course. In the 51 children with complete follow-up, median HbA1c was 7.7 at diagnosis and 6.3 after 2 years. Less than 5 of all children were treated with antihypertensive or lipid-lowering drugs, while 65 suffered from hypertension and 44 from dyslipidemia. Over the course of the disease, retinopathy was not observed, while microalbuminuria occurred in 25. Conclusions:In general practice, many children and adolescents with T2DM were lost of follow-up. Lifestyle intervention as sole treatment was not often useful for long-term metabolic control. Dyslipidemia and hypertension were seldom treated as recommended.Copyright © 2007 S. Karger AG, Basel

To investigate clinical and metabolic characteristics of diabetic children with screening detected celiac disease in a multicenter case-control study.

To investigate the influence of celiac disease (CD) on growth and metabolic control in a nationwide cohort of children and adolescents with type 1 diabetes (T1D).

In persistent hyperinsulinemic hypoglycemia of infancy, ketone body concentrations are abnormally low at times of hypoglycemia, depriving the brain of its most important alternative fuel. The neuroprotective effect of endogenous ketone bodies is evidenced by animal and human studies, but knowledge about exogenous supply is limited. Assuming that exogenous ketone body compounds as a dietetic food might replace this alternative energy source for the brain, we have monitored the fate of orally supplemented dl sodium β-hydroxybutyrate (β-OHB) in two 6-mo-old infants with persistent hyperinsulinemic hypoglycemia for 5 and 7 mo, while on frequent tube-feedings and treatment with octreotide. Near total (95%) pancreatectomy had been ineffective in one patient and was refused in the other. In blood, concentrations of β-OHB increased to levels comparable to a 16- to 24-h fast while on dl sodium β-OHB 880 to 1000 mg/kg per day. In cerebrospinal fluid, concentrations of β-OHB increased to levels comparable to a 24- to 40-h fast, after single dosages of 4 and 8 g, respectively. High ratios of β-OHB to acetoacetate indicated exogenous origin of β-OHB. An increase of intracerebral concentrations of β-OHB could be demonstrated by repetitive single-voxel proton magnetic resonance spectroscopy by a clear doublet at 1.25 ppm. Oral dl sodium β-OHB was tolerated without side effects. This first report on oral supplementation of dl sodium β-OHB in two patients with persistent hyperinsulinemic hypoglycemia demonstrates effective uptake across the blood–brain barrier and could provide the basis for further evaluation of the neuroprotective effect of β-OHB in conditions with hypoketotic hypoglycemia.

In persistent hyperinsulinemic hypoglycemia of infancy, ketone body concentrations are abnormally low at times of hypoglycemia, depriving the brain of its most important alternative fuel. The neuroprotective effect of endogenous ketone bodies is evidenced by animal and human studies, but knowledge about exogenous supply is limited. Assuming that exogenous ketone body compounds as a dietetic food might replace this alternative energy source for the brain, we have monitored the fate of orally supplemented dl sodium -hydroxybutyrate (-OHB) in two 6-mo-old infants with persistent hyperinsulinemic hypoglycemia for 5 and 7 mo, while on frequent tube-feedings and treatment with octreotide. Near total (95) pancreatectomy had been ineffective in one patient and was refused in the other. In blood, concentrations of -OHB increased to levels comparable to a 16- to 24-h fast while on dl sodium -OHB 880 to 1000 mg/kg per day. In cerebrospinal fluid, concentrations of -OHB increased to levels comparable to a 24- to 40-h fast, after single dosages of 4 and 8 g, respectively. High ratios of -OHB to acetoacetate indicated exogenous origin of -OHB. An increase of intracerebral concentrations of -OHB could be demonstrated by repetitive single-voxel proton magnetic resonance spectroscopy by a clear doublet at 1.25 ppm. Oral dl sodium -OHB was tolerated without side effects. This first report on oral supplementation of dl sodium -OHB in two patients with persistent hyperinsulinemic hypoglycemia demonstrates effective uptake across the blood–brain barrier and could provide the basis for further evaluation of the neuroprotective effect of -OHB in conditions with hypoketotic hypoglycemia.

Unrecognized celiac disease (CD) may be found in a substantial proportion of patients with type 1 diabetes mellitus. A cohort of 403 Austrian children and adolescents with type 1 diabetes mellitus (210 males and 193 females; age range, 1–22 years) was screened for celiac disease using the IgA anti‐endomysium antibody test (EMA) and the immunoglobulin (Ig)G anti‐gliadin (AGA‐IgG) and IgA anti‐gliadin (AGA‐IgA) antibody test. Twelve patients' sera (2.98%) yielded positive EMA results and two patients' sera (0.49%) with IgA deficiency had high AGA‐IgG values. All but one of these patients underwent intestinal biopsy. Six (1.49%) had clear histologic evidence of CD (flat mucosa), whereas three (0.74%) showed minor histologic changes (increase in intraepithelial lymphocytes) and four (0.99%), including the EMA‐negative patients with IgA deficiency, had a normal mucosa. When the cases with silent and potential CD were combined, the overall prevalence in the current cohort was 2.98%. There was no difference in the hemoglobin (Hb)A1c level between antibody‐positive and ‐negative patients, and subsequent gluten‐free diet did not change this metabolic parameter. The prevalence of clinically unrecognized CD, found by EMA screening, is much higher in Austrian children with diabetes than in a comparable population without diabetes. The prevalence of CD in diabetic children in Austria is distinctly lower, however, than in several other countries.

The dietary intake of 63 children with insulin‐dependent diabetes mellitus (IDDM; age 10 to 14 years) was weighed by dietitians for 2 days during a summer camp for youth with diabetes. Data were analyzed for the content of macronutrients with the help of a computer database program. The dietary intake of children with diabetes was compared with that of healthy Austrian school children and with the current nutritional recommendations for children with IDDM. The mean intake of carbohydrate did not meet the recommended level, whereas sucrose, fiber, and protein intake approximated the recommendations. The total consumption of fat and cholesterol, however, exceeded the recommended values. The nutritional intake of Austrian children with IDDM was similar to that of healthy children of the same age and thus reflected regional dietary habits. Dietary educational measures on a national basis are needed to change harmful local eating patterns.

Summary: It has been suggested previously that non-enzymatic glycosylation of certain enzymes results in decreased enzymatic activity. In order to examine the role of high blood glucose concentrations (BG) on serum alkaline phosphatase (AP) activity, we determined BG and serum AP in 32 healthy children during an oral glucose tolerance test (OGTT) and in 10 type I diabetic children at 30-min intervals for at least 150 min. A significant negative correlation was noted for BG and AP during the oral glucose load (r=−0.57, p<0.01). In diabetics, however, only children with marked BG fluctuations showed this inverse relationship between BG and AP. These observations could be explained by the formation of a Schiff base as the initial step of non-enzymatic glycosylation of AP. This assumption was further confirmed byin vitro experiments, in which AP was incubated with glucose resulting in decreased enzymatic activity. The dialyzable aldimine formed initially is subsequently stabilized as ketoamine after long-term incubation.

Summary: Eighteen diabetic children aged between 8.5 and 16.5 years (mean 12.5 years) who had been diabetic for 1 to 10 years (mean 4.1 years) were examined for their urinary glomerular basement membrane (GBM) antigen excretion by means of immunoelectrophoresis and for alterations of the retinal vessels by fluorescence angiography. None of these patients showed albuminuria or hypertension. As compared to 40 healthy controls aged between 5 and 17 years, altered GBM antigen mobility (alpha-1) was found in 9 out of these 18 diabetics, whereas the remaining 9 children had normal GBM antigen mobility (alpha-2). Pathological fluorescence angiography findings on the other hand were evident in 7 children with altered GBM mobility, but only in 4 diabetics with normal GBM antigen mobility. This trend reflects the similarity of biochemical and functional characteristics of basement membranes in the retinal and kidney vessels supporting the well established association of vascular changes in both organs in patients with diabetes mellitus. GBM antigen excretion into urine could be useful for detecting early microvascular alterations in the kidneys in juvenile diabetics where diagnosis of early glomerulosclerosis is important.

Abstract. Recently a hypothesis has been proposed suggesting a negative feedback in the regulation of cortisol (F) and melatonin (Mel).To study a possible influence of F on Mel regulation we examined 13 children with congenital adrenal hyperplasia (CAH) on two occasions: once 3 days after cessation of F substitution (group 1; n = 13) and once during treatment with dexamethasone (1 mg/m2/day) and fludrocortisone (0.1 mg/m2/day) (group 2; n = 11) 11 children matched by sex and age served as controls (group 3). While serum 17 OH-progesterone levels, an indicator for the activation of the hypothalamo-pituitary-adrenal axis in CAH, were significantly (P< 0.001) elevated in untreated patients (group 1), serum Mel levels were not different among the 3 groups nor was the diurnal secretion pattern of Mel affected. Nocturnal serum Mel concentrations, however, correlated with the age of the subjects (r = 0.55, P< 0.001 at 23.00 h), displaying high values in early childhood that declined with progressing age.The presented data do not support the view of a classical feedback mechanism in the regulation of Mel and F in humans. However, it confirms the description of a tremendous fall of nocturnal Mel concentrations during childhood.

Although existence of islet cell antibodies (ICA) is regarded as secondary to ß cell death, islet cell surface antibodies (ICSA) might play a role in the disease process. We have collected information from nine European clinics to determine whether ICSA are more common in diabetic children or their relatives in geographical areas or time periods of high incidence of insulin-dependent diabetes mellitus (IDDM). In Finland and Sweden(“North group”) with a high incidence of IDDM during childhood, 36% of the patients were positive or weakly positive for ICSA at diagnosis compared with 24% in France (p = 0.1), 11% in Berlin-Vienna(p < 0.01), and 14% in Italy (p < 0.01). This difference was seen in all age groups but was most pronounced in the youngest(0-4 y). This geographical difference was also seen among family members of whom 46% were positive or weakly positive in the North group, 25% in France(p < 0.001), 21% in Berlin-Vienna (p < 0.001), and 16% in Italy (p < 0.001). Of several analyzed antibodies (ICA, gastric parietal cell, thyroglobulin, and thyroid microsomal), only ICSA showed simultaneous positivity in all family members (r = 0.32,p < 0.01). ICSA were most common in family members of patients with short (<8 d) duration of symptoms (p < 0.05) and showed a similar seasonality, both in patients and relatives, as the incidence of IDDM. We conclude that the geographical difference in incidence of childhood IDDM in Europe may be associated to similar geographical differences in occurrence of ICSA both in newly diagnosed diabetic children and in their relatives. Simultaneous existence of ICSA in both patients and family members and a similar seasonality for ICSA and incidence of IDDM suggest that ICSA may reflect an ongoing disease process.

The aim of this study was to investigate the influence of metabolic control on quantitative electroencephalographic (EEG) abnormalities in young diabetic patients. We compared quantitative EEGs of 44 insulin-dependent diabetic patients with age-matched controls. Furthermore, differences in EEG variables of diabetic patients and controls were correlated with the age of onset and duration of diabetes, hemoglobin A1cconcentrations, and episodes with severe hypoglycemia. We found a correlation between high values of hemoglobin A1cand decreased relative power of the alpha band. Patients with previous ketoacidotic episodes had increased relative power of the delta/theta band and decreased relative power of the alpha band. Patients with hemoglobin A1cvalues less than 8.5% exhibited slowing of background activity compared with normal controls. We conclude that metabolic control influences the EEG and that improvement of glucose metabolism is an important factor in avoiding EEG abnormalities in young diabetic patients. (J Child Neurol1995; 10:330-334).

The high prevalence of low nocturnal blood glucose levels is a major problem in the treatment of children with diabetes.

The high prevalence of low nocturnal blood glucose levels is a major problem in the treatment of children with diabetes. The effect of a ß-glucan–enriched bedtime snack on nocturnal blood glucose levels was examined in comparison with an equicaloric conventional snack in 38 children with diabetes during a 12-night study period. A significant influence of the type of bedtime snack on the blood glucose course until 2 AM could be observed (P< 0.05). However, there was no difference in the prevalence of nocturnal hypoglycemic blood glucose levels, which was 27% at 2 AM. Silent nocturnal hypoglycemia is common in children with diabetes. The introduction of a fiber-enriched bedtime snack may flatten the blood glucose curve before midnight but cannot prevent low 2 AM blood glucose. Other therapeutic strategies that reduce the risk of asymptomatic and symptomatic nocturnal hypoglycemia would be beneficial to many children with diabetes.