Spirometry or Body Plethysmography for the Assessment of Bronchial Hyperresponsiveness?

Methacholine testing is one of the standard tools for the diagnosis of mild asthma, but there is little information about optimal outcome measures. In this study a total of 395 college students were tested by the ATS dosimeter protocol for methacholine testing, with minor modification. Body plethysmography and spirometry were measured after each inhalation step. The end-of-test-criteria were (i) decrease in forced expiratory volume in 1 s (FEV1) of ≥ 20 % and (ii) doubling of specific airway resistance and its increase to ≥ 2.0 kPa∙s. The results were expressed by receiver operating characteristic (ROC) plots using questionnaire answers as a reference. The areas under the ROC curves were iteratively calculated for a wide range of thresholds for both measures. We found that ROC plots showed maximal sensitivities of about 0.5-0.6 for FEV1 and about 0.7 for specific airway conductance (sGt), with similar specificities of about 0.7-0.8 taking questions with the known high specificity as references. Accordingly, larger maximal areas under the ROC curve were observed for body plethysmography, but the differences were small. A decrease in FEV1 of about 15 % and a decrease of sGt of about 60 % showed the largest areas under the ROC curves. In conclusion, body plethysmography yielded better sensitivity than spirometry, with similar specificity. However, replacing the common spirometric criterium for a positive test (20 % decrease in FEV1 from baseline) by the optimal body plethysmographic criterium would result in an increase of false positive tests from about 4 to 8 % in healthy young adults.

Effects of Exposure to Welding Fume on Lung Function: Results from the German WELDOX Study.

The association between exposure to welding fume and chronic obstructive pulmonary disease (COPD) has been insufficiently clarified. In this study we assessed the influence of exposure to welding fume on lung function parameters. We investigated forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and expiratory flow rates in 219 welders. We measured current exposure to respirable particles and estimated a worker's lifetime exposure considering welding techniques, working conditions and protective measures at current and former workplaces. Multiple regression models were applied to estimate the influence of exposure to welding fume, age, and smoking on lung function. We additionally investigated the duration of working as a welder and the predominant welding technique. The findings were that age- and smoking-adjusted lung function parameters showed no decline with increasing duration, current exposure level, and lifetime exposure to welding fume. However, 15% of the welders had FEV1/FVC below the lower limit of normal, but we could not substantiate the presence of an association with the measures of exposure. Adverse effects of cigarette smoking were confirmed. In conclusion, the study did not support the notion of a possible detrimental effect of exposure to welding fume on lung function in welders.

Implementation of non-invasive methods in the diagnosis of diisocyanate-induced asthma.

Diisocyanate-induced asthma is difficult to diagnose since the immunopathological mechanisms and exposure determinants at the workplace are not well defined. The aim of this study was to evaluate the non-invasive methods of nasal lavage fluid (NALF) and induced sputum (IS) to enhance the diagnostic efficiency. Sixty-three diisocyanate-exposed workers with work-related shortness of breath underwent a standardized 4-steps-1-day-whole body exposure test with diisocyanates used at work up to 30 ppb. NALF and IS were collected before, 0.5, and 19 h after the end of exposure. Cellular composition and soluble inflammatory biomarkers were studied in the samples. In addition, ten controls with bronchial hyperresponsiveness, but without prior occupational diisocyanate exposure, were also examined. Twelve out of the 63 subjects (19 %) showed a significant asthmatic reaction (pulmonary responders) after challenge (FEV1 decrease >20 %). NALF samples did not demonstrate significant effects either on cellular composition or on mediator concentrations in the responders, non-responders, or controls at any time point. In contrast, in the IS samples of the pulmonary responders collected 19 h after challenge, the percentage of eosinophils was higher (p = 0.001) compared with baseline before challenge. Eosinophils were also increased 30 min and 19 h after challenge in IS samples of the responders compared with the non-responders or controls. In addition, 19 h after challenge the eosinophilic cationic protein (ECP) concentration was significantly higher in the responders than non-responders (p < 0.04) or controls (p < 0.002). In conclusion, positive asthmatic reactions to diisocyanates are accompanied by an influx of eosinophils into lower airways. Analysis of induced sputum should be implemented in the diagnostic procedure of diisocyanate-related airway diseases.

Evaluation of a 4-steps-1-day whole body challenge protocol for the diagnosis of occupational asthma due to diisocyanates.

Inhalative challenges are important in the diagnosis of occupational asthma due to diisocyanates. As existing protocols are time-consuming and costly, it was the aim of this study to develop a short duration whole body exposure protocol. Ninety three subjects with suspected occupational diisocyanate-induced asthma and verified current or previous occupational exposure to diisocyanates and ten control subjects without diisocyanate exposure but with bronchial hyperresponsiveness were investigated. After baseline examination on the first day, subjects underwent a standardized whole body multiple-steps-1-day challenge with exposures of up to four times 30 min to concentrations of 5, 10, 20, and 30 ppb of the dominant diisocyanate used at work on the second day. Common spirometric and body plethysmographic parameters were used as positivity criteria. Overall, 14 subjects demonstrated a positive diisocyanate challenge, 19 were considered doubtful, and 60 were negative. All controls had negative challenges. Positive reactions occurred during the challenge (n = 10) or during follow-up (n = 4). Eight subjects showed >40 % fall of FEV1. These severe reactions occurred after 5 ppb (n = 2) or 10 ppb (n = 3), while isolated late reactions after 2 h of follow-up were not observed. Multivariate analysis showed an association between a positive challenge and both the degree of previous occupational exposure and the presence of baseline bronchial hyperresponsiveness. In summary, the proposed 4-steps-1-day diisocyanate challenge protocol induced pronounced bronchial reactions in a small number of subjects. As these reactions were more likely to occur after low concentrations, it is recommended to shift the initial concentration/dose step to lower exposures.

Comparison of different non-invasive methods for detection of allergic asthma.

Non-invasive methods to assess inflammation of lower airways are induced sputum (IS), exhaled nitric oxide (eNO), and exhaled breath condensate (EBC). Here we focused on the assessment of airway inflammation with a panel of non-invasive methods in health care workers (HCWs) with suspected latex allergy with and without current allergic respiratory symptoms about 10 years after the latex ban in German health care facilities. Seventy-seven non-smoking subjects were examined by skin prick test and specific IgE measurements, eNO, IS, and EBC. Sensitivity, specificity, and positive and negative predicted values for relevant biomarkers were calculated using current asthma symptoms as the gold standard. Twenty-nine subjects (38%) reported ongoing asthmatic symptoms (AS). In these subjects the EBC concentrations of nitrogen oxides (NO(x); p=0.027) and leukotriene B(4) (p=0.025) were significantly higher than in subjects without AS. In addition, in the subjects with AS the numbers of eosinophils (p=0.015) and the concentrations of IL-5 (p= 0.021) in IS samples were significantly higher than in the subjects without AS. A good correlation between several inflammatory markers in IS was detected. The maximum Youden Index was reached for IS total eosinophils ≥3.5·10(4) with a test efficiency of 0.72. In conclusion, non-invasive inflammatory monitoring with EBC and IS may assist the diagnosis of allergic asthma. Self-reported current asthmatic symptoms were reflected by eosinophilic inflammation and the best parameter to support the asthma diagnosis is a total number of eosinophils ≥3.5·10(4) in IS.

Allergic asthma after flour inhalation in subjects without occupational exposure to flours: an experimental pilot study.

OBJECTIVE: Cross-reactivity between grass pollen and grain flour allergens is well known, but their significance in apprentice bakers with primary sensitization to grass pollen is not known. METHODS: Twenty-five subjects with mild asthma (most of them with hay fever), but without prior occupational flour exposure, underwent standardized experimental inhalation challenges with placebo and wheat and rye flours in randomized order on three consecutive days. Sensitization to flours and environmental allergens was assessed by skin prick tests and specific IgE antibodies in sera. IgE inhibition experiments were performed with wheat and rye flours as solid phases, and grass and tree pollen as inhibitors. RESULTS: Five subjects experienced a positive reaction after flour inhalation (responders), whereas 20 subjects did not show such a reaction (non-responders). All responders showed sensitizations to flours, whereas only 25% of the non-responders demonstrated the same sensitization. Specific IgE concentrations to flours, but also to grass and tree pollen, were higher in responders. Inhibition experiments demonstrated cross-reactivity between flours and grass or tree pollen, with higher inhibition rates in responders. CONCLUSIONS: Subjects with pronounced sensitizations to grass or tree pollen, but without prior occupational exposure to flours, may experience both sensitization and allergic asthmatic reactions to flours due to cross-reactive grass and tree pollen allergens.

The German experience 10 years after the latex allergy epidemic: need for further preventive measures in healthcare employees with latex allergy.

OBJECTIVES: Powdered latex gloves or latex gloves with high allergen content are forbidden in Germany since 1998. It was the aim of this study to test the hypothesis that nationwide preventive measures enable health care workers with latex allergy to work without health risks about 10 years afterwards. METHODS: Ninety-one health care workers who had been reported to the accident insurance between 1996 and 2004 for occupational latex allergy were examined in 2007. The survey included a questionnaire, a physical examination, spirometry, methacholine testing, skin prick testing and serum IgE measurements to latex and environmental allergens. RESULTS: Recent work-related possibly allergic symptoms were reported by 32 subjects (35%), among them 18 subjects (20%) with symptoms of the eyes, nose or airways. Current sensitization to latex was detected in 61 subjects (67%), and 60 subjects (66%) were atopic. Eleven subjects (12%) showed mild airway obstruction, and 27 subjects (30%) were considered hyperresponsive to methacholine. Whereas overall recent symptoms of the eyes, nose or airways were associated with current latex sensitization (OR 4.5; 95% CI 1.3-16.2), this was not the case for objective outcome parameters (spirometry, bronchial hyperresponsiveness). CONCLUSIONS: Although most subjects had only mild disease, ongoing work-related symptoms of the eyes, nose or airways in a substantial number of subjects with latex allergy suggest the need for further secondary preventive measures in German healthcare.

Low discomfort and pain associated with intensified insulin therapy in children and adolescents.

OBJECTIVE: Discomfort during insulin injection and self-monitoring of blood glucose (SMBG) is a potential obstacle in diabetes therapy, but its prevalence and extent in relation to clinical variables is uncertain. RESEARCH DESIGN AND METHODS: We prospectively assessed treatment-associated discomfort and pain in an unselected cohort of patients (60 boys and 52 girls; mean age 14.6+/-3.0 years, mean A1C 8.0+/-1.4%) with type 1 diabetes and multiple daily self-injections of insulin, using visual analogue/verbal rating scales (range, 0-10) and a six-item questionnaire. RESULTS: Pain during insulin injection was absent to very low in 91.9% of patients, and its intensity was independent of age, gender, diabetes duration, current A1C, injection volume, or type of insulin. Injection was more unpleasant than SMBG in 64.2% of patients (mean difference of pain score, 1.0+/-1.7, p<0.0001). Injection into the upper arm was less painful than into the thigh and abdomen. Surprisingly, painlessness of injection and SMBG was not judged an important treatment goal by 22.0 and 32.9% of patients, respectively. Logistic difficulties (41.2% of responses) and time requirements (23.8%), but not pain (10.1%), were considered most relevant problems. CONCLUSIONS: In young patients with access to optimized diabetes care, pain during insulin injection and SMBG is infrequent or mild, and not widely perceived as problematic, thus encouraging the use of multiple daily injection treatment.

Occupational immunoglobulin E-mediated asthma due to Penicillium camemberti in a dry-sausage packer.

A 62-year-old female sausage packer reported progressive work-related asthma, rhinitis and contact urticaria after contact to dry sausages refined by moulds. Whereas skin prick tests with commercial mould extracts were negative, the patient showed weak skin sensitization to a cultivated mould sample from a dry sausage. Specific immunoglobulin E antibodies to various moulds were demonstrated by ImmunoCAP and antibodies to the cultivated mould sample were demonstrated by enzyme allergosorbent test. The mould was identified by pheno- and genotyping as Penicillium camemberti. Five atopic controls did not show sensitization with the same tests. Crossreactivity of P. camemberti and Penicillium notatum was shown by enzyme allergosorbent inhibition tests. Although no challenge tests were considered due to the patient's airway obstruction, a diagnosis of allergic occupational asthma was made. We conclude that immunoglobulin E-mediated allergic occupational asthma due to moulds may occur in dry sausage packers.

Clinical characteristics of type 2 diabetes mellitus in overweight European caucasian adolescents.

AIM: To present the clinical features of Type 2 diabetes mellitus (T2DM) in overweight European Caucasian children and adolescents. METHODS: We report the clinical characteristics of 16 non-syndromal overweight European Caucasian adolescents with T2DM (10 boys, 6 girls, SDS-BMI in median +2.8, range +1.6 to +3.4) treated in 5 specialised centres for obesity and diabetes. RESULTS: None of the adolescents manifested with ketoacidosis. 13 were asymptomatic (3 adolescents with polyuria), 12 showed features of metabolic syndrome (dyslipidaemia or hypertension), 8 demonstrated acanthosis nigricans and 12 had relatives with T2DM. 11 adolescents were extremely obese and all patients were pubertal. Mean age at diagnosis was 14.2 years (range 11.0 - 16.9). Median insulin was 19 microU/ml, insulin resistance index (HOMA) 8.5, C-peptide 2.3 ng/ml, HbA1c 6.9 %, fasting blood glucose 176 mg/dl and blood glucose at 2 hours with the oGTT 229 mg/dl at manifestation. Fasting blood glucose and HBA1c were in the normal range in 4 and 6 adolescents respectively, while oGTT always fitted the diagnosis of T2DM. CONCLUSION: Since T2DM occurred in Caucasian overweight adolescents and is frequently asymptomatic, it is essential that clinicians perform diagnostic procedures to identify T2DM in high-risk groups of overweight Caucasian adolescents (extreme obesity, features of metabolic syndrome, relatives with T2DM).

Type II diabetes mellitus and impaired glucose regulation in Caucasian children and adolescents with obesity living in Germany.

BACKGROUND: Recent studies reported an increased prevalence of type II diabetes mellitus in obese children and adolescents, especially in specific ethnic subgroups. The aim of this study was to determine the prevalence of type II diabetes mellitus and impaired glucose regulation in a large group of Caucasian children and adolescents with obesity living in Germany. PATIENTS AND METHODS: A total of 520 subjects (237 boys, 283 girls) (mean age: 14.0+/-2.0 y (range 8.9-20.4 y)) with a BMI>97th percentile, BMI-SDS: 2.7+/-0.5 (range 1.9-4.6), who were consecutively admitted to an in-patient obesity unit participated in the study. A 2-h oral glucose tolerance test (1.75 mg of glucose per kilogram of body weight) was performed before entering a weight-loss program and capillary blood glucose concentrations were measured. Patients were categorized into normal glucose regulation, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes. In addition, fasting venous blood was taken to determine the circulating insulin, C-peptide and lipids. Insulin resistance was estimated by homeostatic model assessment. RESULTS: Type II diabetes was present in 1.5% (n=8) of the patients, two patients were admitted with already diagnosed type II diabetes and six patients were identified with yet unknown diabetes. IFG was detected in 3.7% (n=19) and IGT in 2.1% (n=11) of the patients. All together, in 6.7% (n=35) (95% confidence interval: 4.7-9.2%) of the patients, impaired glucose regulation (IFG, IGT) or diabetes was identified. These patients had a higher BMI-SDS, higher levels of fasting insulin and C-peptide and a higher insulin resistance index than the patients with normal glucose regulation. Risk factors for the occurrence of impaired glucose regulation were a BMI-SDS>2.5 as well as a positive parents' history for diabetes. CONCLUSIONS: This is the first report on the prevalence of type II diabetes in a large cohort of Caucasian children and adolescents with obesity living in Europe. Impaired glucose regulation and type II diabetes were present in a substantial proportion of the patients studied. Screening for diabetes in severely obese children and adolescents (BMI-SDS>2.5) is therefore recommended. Patients identified with impaired glucose regulation need specific treatment programs in order to prevent progression to diabetes.

[Evaluation of an outpatient treatment program for obese children and adolescents]. / Ergebnisse einer ambulanten Behandlung von Kindern und Jugendlichen mit Adipositas.

BACKGROUND: In Germany the number of children with elevated body weights has significantly increased in the last 10 to 15 years. Resulting comorbidities lead to increasing costs for the community. The quality of life of these children is reduced. PATIENTS: 84 children and their families have been included in the study. In addition to anthropometric data informations on eating behaviour and psychosocial data of the family have been documented. At the beginning of the intervention the children had an age of 10.36 +/- 3,27 years and a BMI-SDS of 4,78 +/- 1,16. The mean time period for follow-up has been 28,7 months (mean). METHODS: Children have been treated within a family-based intervention program in a setting focusing on behaviour modification over 6 months (sessions every 4 th week). Patients have been treated in four different intervention groups (behaviour modification and eating counselling (a),a' plus one parent group session (b),b' plus two courses in cooking and preparing meals for parents and children, (c), the fourth group has been treated in addition within a more intensive inpatient setting for 6 weeks. RESULTS: Drop out rate has been 37,1 %. The weight reduction during the treating period has resulted in a reduction of the BMI-SDS of 0.57 +/- 0.51 (p = 0.0001). 33.7 % of the patients investigated during follow-up (n = 30) have not changed or even reduced their achieved body weights (BMI-SDS). In a stepwise multiple regression analysis the variables age of the patient, self-control of eating behavior and weight of the father explained 70 % of the variance of weight changes during the follow-up period. There have been no differences between the changes in BMI-SDS during follow-up between patients in groups,a',b' or,c' and the group taking part in addition in the in-patient setting. CONCLUSIONS: Treatment programs for obese children and adolescents have to focus on the specific living conditions and eating behaviours of the family especially on age, capacity for self control of the child and the eating behaviour of the father. Local networks to be established within the country for treating obese children coordinated by the paediatrician seem to be best possibilities to provide individual support. In this local networks the prevention of extreme eight increases must be a predominant task.

Serum leptin, gonadotropin, and testosterone concentrations in male patients with anorexia nervosa during weight gain.

Amenorrhea in female patients with anorexia nervosa is associated with low leptin secretion, thus suggesting a causal link. In an attempt to address the hypothesis that leptin also influences the hypothalamo-pituitary-gonadal function in males, we studied three male patients with acute anorexia nervosa longitudinally. Serum levels of leptin, LH, FSH, testosterone, and SHBG were measured on a biweekly basis during weight gain. Leptin levels at low body mass index values were below the 5th percentile. During weight gain, leptin levels reached or surpassed the 95th percentile. The temporal dynamics of body mass index and fat mass were closely related to those of leptin concentrations in serum. Leptin increments were paralleled by increments of gonadotropins, testosterone, and the free androgen index (FAI). In each of the patients, serum concentrations of leptin were positively correlated with those of testosterone (P = 0.0001, P = 0.01, P = 0.07, respectively) and FAI (P = 0.0001, P = 0.0001, P = 0.09, respectively). In addition, in the combined data set of all patients changes of leptin over time were positively correlated with changes in LH (P = 0.01), FSH (P = 0.0001), testosterone (P = 0.002), and FAI (P = 0.002). In conclusion, these data suggest that leptin might also play an important role in the regulation of the hypothalamo-pituitary-gonadal axis and fertility in underweight males as has previously been shown in underweight females.

Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation.

OBJECTIVE: To develop and to characterize a human preadipocyte cell strain with high capacity for adipose differentiation serving as a model for studying human adipocyte development and metabolism in vitro. METHODS: Cells were derived from the stromal cells fraction of subcutaneous adipose tissue of an infant with Simpson-Golabi-Behmel syndrome (SGBS). Adipose differentiation was induced under serum-free culture conditions by exposure to 10 nM insulin, 200 pM triiodothyronine, 1 microM cortisol and 2 microM BRL 49653, a PPAR gamma agonist. RESULTS: During the differentiation process SGBS cells developed a gene expression pattern similar to that found in differentiating human preadipocytes with a characteristic increase in fat cell-specific mRNAs encoding lipoprotein lipase (LPL), glycero-3-phosphate dehydrogenase (GPDH), GLUT4, leptin and others. Differentiated SGBS cells exhibited an increase in glucose uptake upon insulin stimulation and in glycerol release upon catecholamine exposure. SGBS adipocytes were morphologically, biochemically and functionally identical to in vitro differentiated adipocytes from healthy subjects. However, while preadipocytes from healthy control infants rapidly lost their capacity to differentiate after a few cell divisions in culture, SGBS cells maintained their differentiation capacity over many generations: upon appropriate stimulation 95% of SGBS cells of generation 30 developed into adipocytes. A mutation in the glypican 3 gene was not detected in the patient. Thus, it remains unclear whether the molecular alteration in SGBS cells is also responsible for the high differentiation capacity and further investigations are required. CONCLUSION: The human cell strain described here provides an almost unlimited source of human preadipocytes with high capacity for adipose differentiation and may, therefore, represent a unique tool for studying human fat cell development and metabolism. International Journal of Obesity (2001) 25, 8-15

Hemoglobin A1c and body mass index in children and adolescents with IDDM. An observational study from 1976-1995.

In adult patients with type 1 diabetes good metabolic control was associated with an undesired weight gain. In the present report the possible association of HbA1c and body mass index (BMI) in children and adolescents with type 1 diabetes (IDDM) was investigated in a long-term retrospective study from 1976 to 1995. Further, the relationship between BMI on one hand and age, gender, duration of IDDM, the number of units of insulin used and the number of injections per day on the other hand were considered. Statistical analysis was performed using repeated measurements analyses of variance. The 208 girls and 201 boys were 5-17 years old and had diabetes for beyond one year. For analysis 2512 data sets, in part measurements on the same patient in the course of the disease, were available. In various statistical models, the results show that age, gender, the daily amount of insulin, and the HbA1c level (p<0.001-0.005) were associated with the BMI. Extremely high HbA1c levels coincided with a remarkably low BMI. Hence, in children and adolescents with IDDM it may be difficult to achieve a constantly good metabolic control accompanied by a normal body weight.

IGF-I- and IGFBP-3-expression in cultured human preadipocytes and adipocytes.

The expression and secretion of IGF-I and IGFBP-3 were investigated in cultured human preadipocytes and in in vitro differentiated adipocytes derived from human subcutaneous adipose tissue under chemically defined culture conditions. Human preadipocytes expressed mRNAs for IGF-I and IGFBP-3 and secreted the corresponding proteins into the culture medium as measured by sensitive radioimmunoassays. In human adipocytes; specific mRNA-expression was comparable to that found in preadipocytes, but IGF-I secretion was increased 10-fold (3.87 +/- 0.69 vs. 0.41 +/- 0.11 ng/ml/10(6) cells/48 hrs, p < 0.05) and IGFBP-3 secretion 2.5-fold (7.34+/-1.15 vs. 3.27+/-0.38 ng/ml/10(6) cells/48 hrs, p<0.05) in the presence of adipogenic medium probably resulting in an increase of unbound IGF-I. Under serum-free, chemically defined conditions human growth hormone (hGH) and insulin were found to be positive regulators and cortisol was found to be a negative regulator of IGF-I and IGFBP-3 secretion in preadipocytes. In cultured human adipocytes, hGH showed no effect on IGF-I and IGFBP-3 secretion, whereas insulin stimulated and cortisol inhibited the secretion of both proteins. We conclude that IGF-I and IGFBP-3 may not only exert their actions in human adipose tissue via circulation, but also in an auto/paracrine way.

Urinary excretion of albumin in adolescents with type 1 diabetes: persistent versus intermittent microalbuminuria and relationship to duration of diabetes, sex, and metabolic control.

OBJECTIVE: Urinary excretion of albumin is a marker for incipient diabetic nephropathy in adults. The intra-individual variability, as well as the relationship to duration of diabetes, onset of the disease, and long-term metabolic control, have not been evaluated in a large sample of pediatric patients. RESEARCH DESIGN AND METHODS: A total of 5,722 nocturnal urinary albumin excretion rates were determined in 447 children, adolescents, and young adults with type 1 diabetes, comprising 1,821 years of observation. Excretion rates were related to duration of diabetes, age at onset of diabetes, sex, blood pressure, and metabolic control. RESULTS: Based on repeated measurements in individual patients, the positive predictive value of one sample was 76%, the negative 99.5%. After a duration of diabetes of 11 years, 5% of patients displayed persistent microalbuminuria (10% after 13 years). The duration of diabetes until persistent microalbuminuria was identical for patients with prepubertal or pubertal onset of diabetes. In addition to duration, female sex (P < 0.03) and insufficient long-term metabolic control (P < 0.03) contributed significantly and independently to urinary albumin excretion. CONCLUSIONS: Determination of urinary albumin excretion rate is useful in pediatric patients. Female subjects with a long duration of diabetes and insufficient metabolic control are especially at risk for microalbuminuria. Even if persistent microalbuminuria usually becomes evident in patients aged > 11 years, the prepubertal duration of diabetes contributes equally to this risk. Good metabolic control therefore should be aspired to from the onset of diabetes.

Circadian blood pressure during the early course of type 1 diabetes. Analysis of 1,011 ambulatory blood pressure recordings in 354 adolescents and young adults.

OBJECTIVE: Little information is available on the early course of hypertension in type 1 diabetes. The aim of our study, therefore, was to document circadian blood pressure profiles in patients with a diabetes duration of up to 20 years and relate daytime and nighttime blood pressure to duration of diabetes, BMI, insulin therapy, and HbA1c. RESEARCH DESIGN AND METHODS: Ambulatory profiles of 24-h blood pressure were recorded in 354 pediatric patients with type 1 diabetes (age 14.6 +/- 4.2 years, duration of diabetes 5.6 +/- 5.0 years, follow-up for up to 9 years). A total of 1,011 profiles were available for analysis from patients not receiving antihypertensive medication. RESULTS: Although daytime mean systolic pressure was significantly elevated in diabetic subjects (+3.1 mmHg; P < 0.0001), daytime diastolic pressure was not different from from the height- and sex-adjusted normal range (+0.1 mmHg, NS). In contrast, both systolic and diastolic nighttime values were clearly elevated (+7.2 and +4.2 mmHg; P < 0.0001), and nocturnal dipping was reduced (P < 0.0001). Systolic blood pressure was related to overweight in all patients, while diastolic blood pressure was related to metabolic control in young adults. Blood pressure variability was significantly lower in girls compared with boys (P < 0.01). During follow-up, no increase of blood pressure was noted; however, diastolic nocturnal dipping decreased significantly (P < 0.03). Mean daytime blood pressure was significantly related to office blood pressure (r = +0.54 for systolic and r = +0.40 for diastolic pressure); however, hypertension was confirmed by ambulatory blood pressure measurement in only 32% of patients with elevated office blood pressure. CONCLUSIONS: During the early course of type 1 diabetes, daytime blood pressure is higher compared with that of healthy control subjects. The elevation of nocturnal values is even more pronounced and nocturnal dipping is reduced. The frequency of white-coat hypertension is high among adolescents with diabetes, and ambulatory blood pressure monitoring avoids unnecessary antihypertensive treatment.

Suppression of growth hormone by oral glucose in the evaluation of tall stature.

Excess secretion of growth hormone is a rare diagnosis in children or adolescents with tall stature. An oral glucose tolerance test (OGT) with determination of growth hormone is generally recommended to exclude this disorder. In order to test the validity of this approach in pediatric subjects, OGT tests were performed in 126 tall subjects (age: 12.4 +/- 1.8 years; height: 3.1 +/- 0.8 SDS). Nonsuppression was present in 39 subjects, however, anthropometric analysis and follow-up excluded the diagnosis of eosinophilic pituitary adenoma in all patients. The lowest GH concentration was reached 90 min after ingestion of oral glucose, GH rose above baseline at 180 min. Plasma concentrations of glucose and insulin did not differ between suppressors and nonsuppressors. In conclusion, absent suppression of growth hormone by oral glucose is common in tall children and adolescents. The test is therefore not recommended as a general screening for excess growth hormone. Prolonging the test beyond 120 min does not increase the diagnostic value.

Angiotensin I converting enzyme and angiotensinogen gene polymorphisms related to 24-h blood pressure in paediatric type I diabetes mellitus.

UNLABELLED: The aim of this study was to evaluate two putative predictive genetic markers for hypertension in children and adolescents with diabetes mellitus. Ambulatory blood pressure measurements were performed in 199 patients with type I diabetes mellitus (mean age 16.5 years, mean duration of diabetes 7.7 years) and compared to those of 1141 healthy children. The local allele frequencies were established based on a control population consisting of 181 healthy subjects. The allele frequencies of the angiotensinogen gene M235T polymorphism was nearly identical in insulin-dependent diabetes mellitus patients (MM 33%, MT 51%, TT 16%) and controls (MM 35%, MT 49%, TT 16%). In contrast, the genotype distribution of the angiotensin I converting enzyme gene insertion/deletion (I/D) polymorphism was different between patients with type I diabetes mellitus (DD 26%, ID 49%, II 25%) and the control group (DD 37%, ID 44%, II 19%) (P=0.04). Relative nocturnal systolic and diastolic pressures in patients with diabetes were higher than in healthy age- and height-matched controls; no association was found with the angiotensinogen gene M235T polymorphism. Relative nocturnal diastolic blood pressure was higher in patients homozygous for the I allele of the angiotensin I converting enzyme gene. CONCLUSION: Nocturnal systolic and diastolic blood pressure is higher in patients with type I diabetes than in healthy children. The formerly described, but controversial, association of the M235T polymorphism with arterial hypertension could not be confirmed in this study.