Vulvovaginal candidiasis in children and adolescents with type 1 diabetes mellitus

In this prospective study we investigated the frequency of vulvovaginal candidiasis, the results of yeast cultures and detection of ketoconazole resistance in female children and adolescents with type 1 diabetes mellitus (DM1). The study consisted of 35 patients with DM1 (age 1.7-20 years) and 22 controls (age 1.5-18 years). Age, duration of DM1 and evidence of genital symptoms were recorded initially. After a pelvic examination, two separate swabs and samples for blood glucose and hemoglobin A1c (HbA1c) were taken. One of the swabs was used for direct examination and the second was placed on Sabouraud's dextrose agar and incubated. In vitro susceptibility of Candida species to ketoconazole was established by using Etest (AB B1ODISC). Candida species were isolated in 32 of 61 (52.5%) swabs of patients with DM1 and five of 22 (18.2%) of the control group. The predominant Candida species isolated from patients with DM1 were C. albicans (72.7%), C. glabrata (22.7%), C. tropicalis (2.3%), and C. parapsilosis (2.3%). The mean HbA1c in diabetic patients from whom Candida species were isolated was significantly higher than that of patients without Candida infection (p = 0.002). Most of the C. glabrata isolates were significantly resistant to ketoconazole. During the follow-up of patients with DM1, genital candidiasis is generally overlooked. It should not be forgotten that species other than C. albicans might cause genital candidiasis.     

Lipoprotein composition in children and adolescents with type 1 diabetes mellitus

Atherosclerotic cardiovascular diseases are the major causes of morbidity and mortality in patients with diabetes mellitus. Both quantitative and qualitative abnormalities of lipo-proteins are associated with the development of atherogenesis. In this study, the prevalence of dyslipidemia and the relative levels of glycosylated lipoproteins in 20 children and adolescents with type 1 diabetes mellitus were determined. Lipid profile, apolipoproteins A-I and B, Lp(a) and LpA-I in plasma were assayed. LpB and glycosylated HDL and LDL were evaluated by ELISA. Diabetic patients and controls had normal lipid profiles, but the diabetic group showed significantly higher LpA-I and lower LpA-I:A-II concentrations than controls. The diabetic group showed a significantly higher glycosylation level of HDL than controls and did not show a statistical difference for glycosylated LDL. No significant correlation between glycosylated lipoproteins, glycemia or HbA1c was found. In conclusion, these results suggest that type 1 diabetic patients develop important qualitative lipid abnormalities.     

Bone maturation in 1788 children and adolescents with diabetes mellitus type 1

Diabetes mellitus type 1 might interfere with pubertal development. Particularly, long-term metabolic control and intensity of insulin treatment have been reported to contribute to a delay in pubertal onset. Data on somatic development in diabetic children are conflicting; therefore we studied bone age in 1788 children from Germany and Austria with type 1 diabetes. Bone age was retarded by -0.27 +/- 1.1 years in the whole group, but particularly in the adolescents at the end of puberty (>16 years; -0.76 +/- 1.29y). Bone age delay was more pronounced in boys, and in children with long-term median HbAlc levels of 7.5 - 9.0%. No associations were found with current HbAlc levels or the intensity of insulin treatment. Bone age determinations in diabetic children should only be performed when clinical signs of impaired somatic development are present. In addition, the potential influence of diabetes on bone development needs to be considered in the interpretation of carpograms.     

Initial insulin therapy in children and adolescents with type 1 diabetes mellitus

Weitzel D, Pfeffer U, Dost A, Herbst A, Knerr I, Holl R. Initial insulin therapy in children and adolescents with type 1 diabetes mellitus. Objective: The aim of the study was to define parameters that influence the initial insulin dosage in young subjects with type 1 diabetes regarding the amount of daily insulin, the ratios of basal and prandial insulin, and the insulin/carbohydrate ratios. Study design: We used a computer‐based registry (with prospectively collected data) in Germany and Austria, a software for the management and data documentation of diabetic patients (DPV), to analyze the initial insulin therapy in 2247 children with newly diagnosed type 1 diabetes to identify factors that influence diabetes therapy within the first 10 d. Results: For both genders, glucosylated hemoglobin A1c (HbA1c), blood pH at diabetes onset, and pubertal status are the major factors determining the initial insulin dosage calculated as the amount of daily insulin per kilogram body weight (kg), the basal and prandial insulin dose per kilogram, and day and the insulin/carbohydrate ratios for meals. The frequency of hypoglycemia correlated with increasing quotient of applied to calculated insulin dosage. Conclusion: The predictive factors of insulin requirement may exert beneficial effects on the assessment and adjustment of insulin therapy in young diabetic subjects at disease onset. On the basis of a multiple, linear regression, we suggest a formula to calculate the initial insulin therapy.     

Predictors of glucose control in children and adolescents with type 1 diabetes mellitus

AIMS: To evaluate the glucose control [(as measured by hemoglobin A1c (HbA1c)], the factors associated with glycemic control, and possible explanations for these associations in a sample of children and adolescents with type 1 diabetes. METHODS: Data were collected on 155 children and adolescents, with type 1 diabetes mellitus, attending a multidisciplinary diabetes clinic in Portland, OR. Patients' hospital charts were reviewed to determine demographic factors, disease-related characteristics, and HbA1c level. RESULTS: Mean percent HbA1c was 9.3. Adolescents between the ages of 14 and 18 yr were in poorer metabolic control (adjusted mean percent HbA1c 0.56 higher than children 2-8 yr). Children who attended the clinic three to four times in the previous year were in better control (adjusted mean percent HbA1c 0.46 lower than those who visited two or fewer times and 1.11 lower than those who attended five or more times). Children with married parents were in better glycemic control than those of single, separated, or divorced parents (adjusted mean percent HbA1c 0.47 lower for children of married parents). This effect appeared to be mediated, in part, by the number of glucose checks performed per day. CONCLUSIONS: This study suggests that adolescents should be targeted for improved metabolic control. Diabetes team members need to be aware of changing family situations and provide extra support during stressful times. Regular clinic attendance is an important component of intensive diabetes management. Strategies must be developed to improve accessibility to the clinic and to identify patients who frequently miss appointments.     

Autonomic blood pressure control in children and adolescents with type 1 diabetes mellitus

Introduction:  Increased daytime blood pressure and reduced nocturnal dipping can already be found in children with type 1 diabetes mellitus. We hypothesized that impaired baroreflex sensitivity can cause this abnormal blood pressure behavior in children and adolescents with type 1 diabetes, reflecting an early stage of diabetic autonomic neuropathy.
Methods:  In the present study, we monitored beat-to-beat blood pressure and pulse interval non-invasively with portapres© in 38 patients with type 1 diabetes (7–18 yr) and 14 non-diabetic subjects (5–17 yr). The Trigonometric Regressive Spectral Analysis was used to assign spontaneous oscillations of blood pressure and pulse interval to defined frequency bands between 0.003 and 1.0 Hz and to calculate baroreflex sensitivity. Correlations with diabetes-specific data like hemoglobin A1c (HbA1c) and with 24-h blood pressure measurements were calculated.
Results:  The diabetic subjects displayed significantly less variance of blood pressure and pulse interval in the high frequency (HF) bands and a lower BRS. BRS decreased with higher HbA1c and daily insulin dose. We also saw significant changes in spectral variance of blood pressure and pulse interval with these parameters. Patients with higher sympathetic activity (LF/HF-ratio) during daytime measurements displayed more nocturnal dipping.
Conclusion:  Our data evidence impaired baroreflex sensitivity in children and adolescents with type 1 diabetes mellitus. We suggest spectral analysis of spontaneous blood pressure and pulse interval oscillations during night sleep to further pursue the role of baroreflex sensitivity in the etiology of the non-dipping phenomenon in diabetic patients.     

Treatment of hypertension and microalbuminuria in children and adolescents with type 1 diabetes mellitus

Abstract: Nephropathy is the main cause of morbidity and mortality in patients with type 1 diabetes and, in adults, persistent microalbuminuria is the best marker of the consequent risk for its development. In the pediatric population, puberty represents the most important risk factor for the development of microangiopathic complications, although it is not necessarily associated with the progression to frank proteinuria. As many as 50% of subjects may revert to normoalbuminuria. Hypertension is a further risk factor and may accelerate the progression of micro- and macrovascular complications. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce renal damage by one or more mechanisms independent of their antihypertensive effects – hence they represent the drug of choice for the treatment of diabetic nephropathy. However, as angiotensin II receptor antagonists are more specific, they may become the obvious treatment choice in the near future. There is no consensus as to who should be treated and when treatment with renoprotective drugs should begin in the pediatric population, due to the lack of a clear definition of the natural history of microalbuminuria in this age group. In this review some models and controversial aspects of this issue are presented and discussed.     

Prevalence of overweight and obesity in children and adolescents with type 1 diabetes mellitus

BACKGROUND: Information about the prevalence of obesity in children with type 1 diabetes mellitus (DM1) is inconsistent and limited. The burden of the concurrent problems of obesity and DM1 can have notable medical, psychological, and social implications for both patients and their families. AIMS: To determine prevalences of overweight and obesity in children with DM1 compared to a control population. METHODS: In a cross-sectional study, we compared the prevalence of overweight/obesity in 390 children with DM1 (males 54%) and 565 controls (CONT; males 60%) aged 6 to 16 years. Overweight and obesity were defined as body mass indices between the 85th and 95th percentiles, and greater than the 95th percentile for age, respectively. RESULTS: Overall, 29.5% DM1 and 18.1% CONT (p < 0.001) were either obese or overweight. The prevalence of obesity alone did not differ (DM1 5.4% vs CONT 8.2%), but a greater rate of overweight was seen in the DM1 group (DM 24.1% vs CONT 10.0%, p < 0.001). Rate's of overweight were higher in the DM1 than CONT across all age groups and in both genders (males: DM1 20.1% vs CONT 8.9%, p < 0.001; females: DM1 28.7% vs CONT 11.5%, p < 0.001). Only females showed an increase in overall overweight/obesity rate (DM1 34.8% vs CONT 16.4%, p < 0.001) and this was most evident in older girls. CONCLUSIONS: Children with DM1 are more overweight, but not more obese, than their nondiabetic counterparts. Additional research is warranted to evaluate the characteristics of DM1 and its management that may influence weight gain.     

儿童和青少年1型糖尿病流行病学及治疗研究进展

1型糖尿病作为儿童和青少年糖尿病的主要类型,近20年来发病率有明显的增加趋势,引起全世界越来越多的关注.该文综述了近年来国内外儿童和青少年1型糖尿病流行病学、治疗和管理方面的研究进展,通过对比国内外儿童和青少年糖尿病学研究进展,可以更好地了解我国儿童糖尿病研究方面与世界研究方面的差距,从而为我国以后的研究指明方向.     

Prevalence of celiac disease in Brazilian children and adolescents with type 1 diabetes mellitus

OBJECTIVE: A previously unrecognized high prevalence of celiac disease (CD) has been found by screening among European and North American patients with type 1 diabetes mellitus (DM 1). The prevalence of CD among Brazilian children with DM1 is not known. This study was conducted to determine the prevalence of CD in Brazilian children and adolescents with DM 1. METHODS: One hundred and four children and adolescents with DM 1 (52 males and 52 females; age range 22 months - 19 years) and 105 age and gender-matched control participants were screened for CD using the IgA anti-endomysial antibody test (IgA-EmA) and total serum IgA. A small bowel biopsy was performed in all patients with positive IgA-EmA. RESULTS: Nine of 104 diabetic patients (8.7%) had a positive IgA-EmA. Biopsies were normal in four patients, two had partial or subtotal villous atrophy with elevated intraepithelial lymphocyte (IEL) counts, and three showed partial villous atrophy but with IEL counts under the maximum limit adopted (40 IEL/100 enterocytes). EmA-IgA positive patients had mild, non-specific gastrointestinal complaints including dyspepsia, abdominal pain, flatulence and constipation. All control participants had negative results for IgA-EmA. CONCLUSION: The prevalence of CD in a group of Brazilian pediatric DM 1 patients was at least 4.8%, a prevalence comparable to European and North American studies. The high prevalence of CD among DM 1 emphasizes the need for routine screening in all countries including Brazil.     

Early predictors of myocardial disease in children and adolescents with type 1 diabetes mellitus

Background: The spectrum of diabetic heart disease involves a progression from normal heart to preclinical left ventricular diastolic and systolic dysfunction followed by overt echocardiographic evidence of left ventricular (LV) dysfunction and finally symptomatic heart failure. Objective: To compare the value of tissue Doppler imaging (TDI) over the conventional echocardiography in the assessment of early myocardial dysfunction in type 1 diabetics in correlation with serum N‐terminal pro‐brain natriuretic peptide (NT‐pro‐BNP), state of metabolic control, and diabetes duration. Methods: Sixty subjects were included; 40 type 1 diabetics (aged 12–18 years). Twenty matched subjects served as controls. They were subjected to clinical examination with assessment of cardiovascular reflexes for autonomic neuropathy. Laboratory investigations included mean random blood sugar (MRBS), hemoglobin A1c (HbA1c), urinary microalbumin, and serum determination of NT‐pro‐BNP. Echocardiography for chamber dimensions, systolic and diastolic function, Tie index, and longitudinal myocardial global biventricular function by pulsed TDI of 6 LV walls and right ventricle (RV) free wall. Results: All diabetics and controls had normal LV dimensions, LV mass index and systolic functions except for higher left ventricular posterior wall (LVPW) in diabetics (P < 0.05). LV and RV diastolic dysfunction diagnosed in 25% of diabetics by conventional Doppler with higher peak A (P < 0.05, P < 0.05) and lower E/A (P < 0.05, P < 0.05) compared to controls. Diabetics had larger Tie index (P < 0.05). TDI showed delayed myocardial relaxation in 52.5% of diabetics with lower LV and RV peak Em (P < 0.05, P < 0.01) and Em/Am (P < 0.01, P < 0.001) compared to controls. NT‐pro‐BNP was elevated in diabetics (P < 0.01) with best cut‐off value = 62.5 Fmol/mL, sensitivity (82%), and specificity (95%) for detection of isolated diastolic dysfunction in diabetics. It was correlated negatively with LV Em (P < 0.05), Em/Am (P < 0.01) and positively with Am (P < 0.01), impaired diastolic velocities were associated with higher HbA1c. Conclusion: Asymptomatic diabetics had evidence of subtle right and LV dysfunction with delayed myocardial relaxation which was related to metabolic control. Tissue Doppler (TD) has an additional value in evaluating ventricular filling. NT‐pro‐BNP is considered a sensitive, specific, and predictive marker for diastolic dysfunction.     

Hypoglycemia, hypoglycemia unawareness and counterregulation in children and adolescents with type 1 diabetes mellitus

Three clinical phenomena have been defined in the last decade in patients with diabetes mellitus as a dangerous iatrogenic sequel of hypoglycemia. These are hypoglycemia unawareness, defective glucose counterregulation and a lowered hypoglycemic threshold for hypoglycemic symptoms. Former mild hypoglycemia episodes cause a decrease and a delay in the protective hormonal counterregulatory response and warning symptoms in subsequent episodes, and in the absence of these, risk of severe hypoglycemia increases considerably. It has been demonstrated that when protection is provided against hypoglycemia with strict monitoring programs designed to avoid even mild hypoglycemia episodes, blunted autonomic symptoms and counterregulatory hormonal responses are rectified. Therefore, the best course of action in the treatment of pediatric diabetes mellitus is frequent blood sugar measurements, flexible multiple dose insulin regimens facilitating insulin dose adjustments as required, and a diet. In order to implement this, it is essential to organize an intensive training program with the patient and family, and to provide psychological support and close coordination with the diabetes treatment team.     

Autonomic neuropathy and gastrointestinal motility disorders in children and adolescents with type 1 diabetes mellitus

INTRODUCTION: There is little information on the gastrointestinal motility abnormalities and autonomic neuropathy of children with gastrointestinal symptoms and type 1 diabetes mellitus (T1DM). METHODS: The authors studied 33 consecutive patients (mean age, 15.3 years; 13 males) with T1DM (median duration, 7.7 years) attending the outpatient clinic because of chronic dyspepsia (CD; n = 14), or chronic constipation (CC; n = 19), and 48 consecutive non-T1DM patients (mean age, 13.7 years; 18 males), who presented with similar symptoms (18 with CD; 30 with CC). Fasting serum motilin concentrations and cardiovascular autonomic function tests (CAFT) were assessed and compared with those of age- and gender-matched healthy control subjects. Gastric emptying half time (GE t1/2) of a solid meal and mouth-to-anus transit time (MATT) were measured in patients with CD and CC, respectively. RESULTS: CAFT was comparable between patients with T1DM and healthy control subjects. GE t1/2 and MATT were not different between T1DM patients and non-T1DM patients with CD and CC, respectively. However, a marginally significant positive correlation was found in the patients with T1DM between GE t1/2 and blood glucose concentrations (R = 0.54; P = 0.08). In addition, serum motilin concentrations were significantly lower in patients with T1DM compared with healthy control subjects (P < 0.0005), and in patients with T1DM and higher serum glucose concentrations compared with those with lower serum glucose concentrations (P = 0.03). CONCLUSION: Autonomic neuropathy is not an etiological factor of gastrointestinal symptoms in children and adolescents with diabetes. Mild or moderate hyperglycemia does not affect gastrointestinal motility.