Cholecalciferol supplementation improves suppressive capacity of regulatory T-cells in young patients with new-onset type 1 diabetes mellitus - A randomized clinical trial.

It is unknown if cholecalciferol is able to modify defects in regulatory T cells (Tregs) in type 1 diabetes (T1D). In this randomized, double-blind, placebo controlled trial 30 young patients with new-onset T1D were assigned to cholecalciferol (70IU/kgbodyweight/day) or placebo for 12months. Tregs were determined by FACS-analysis and functional tests were assessed with ex vivo suppression co-cultures at months 0, 3, 6 and 12. Suppressive capacity of Tregs increased (p<0.001) with cholecalciferol from baseline (-1.59±25.6%) to 3 (30.5±39.4%), 6 (44.6±23.8%) and 12months (37.2±25.0%) and change of suppression capacity from baseline to 12months was significantly higher (p<0.05) with cholecalciferol (22.2±47.2%) than placebo (-16.6±21.1%). Serum calcium and parathormone stayed within normal range. This is the first study, which showed that cholecalciferol improved suppressor function of Tregs in patients with T1D and vitamin D could serve as one possible agent in the development of immunomodulatory combination therapies for T1D.

Why is insulin pump treatment rarely used in adolescents and young adults with cystic fibrosis-related diabetes?

BACKGROUND: In type 1 diabetes (T1D), the use of continuous subcutaneous insulin infusion (CSII) has increased steadily in the last years. Compared with conventional insulin injection regimes, major advantages might be a nearly physiological insulin secretion, lower rates of hypoglycemia, higher flexibility in daily life, and increased quality of life. Data on CSII in cystic fibrosis-related diabetes (CFRD) are scarce. OBJECTIVE: To analyze current use of insulin pumps in CFRD and compare demographics of pump-treated patients between CFRD and T1D. METHODS: Data from the prospective German/Austrian diabetes patient registry on insulin-treated patients with either CFRD (n = 515) or T1D (n = 43 165) aged >10 yr at manifestation of diabetes were analyzed. RESULTS: A total of 4.1% (n = 21) of CFRD and 17.7% (n = 7647) of T1D patients received insulin pump treatment within the recent year of care (p < 0.001). Pump-treated patients with CFRD had a significantly shorter duration of diabetes [median (Q1 ; Q3 ): 5.8 (2.9; 9.5) vs. 7.8 (4.3; 20.4) yr, p = 0.026] and tended to be younger [22.0 (18.2; 30.1) vs. 24.9 (17.3; 45.9) yr] than pump-treated T1D patients. Age at initiation of CSII seemed to be lower in CFRD [19.2 (16.5; 29.2) vs. 23.3 (14.8; 43.5) yr]. Insulin pump therapy was used slightly more often in male CFRD patients than females (4.7 vs. 3.6%), whereas in T1D the opposite was observed (14.9 vs. 21.2%, p < 0.001). Discontinuation rate of CSII was higher in CFRD than T1D (30.0 vs. 12.7%, p = 0.005). CONCLUSIONS: Despite potential advantages, insulin pump therapy was rarely used among adolescent and young adult CFRD patients.

Weight and body mass index (BMI): current data for Austrian boys and girls aged 4 to under 19 years.

BACKGROUND: BMI reference charts are widely used to diagnose overweight, obesity and underweight in children and adolescents. AIM: To provide up-to-date national reference values for Austria. METHODS: A cross-sectional sample of over 14 500 children and adolescents (4-19 years) stratified by provinces according to age- and sex-specific population proportions was drawn via schooling institutions (kindergartens, schools and vocational colleges). The generalized additive models for location, scale and shape were used for a flexible estimation of percentile curves. RESULTS: Austrian boys and girls have higher average weight compared with previous prevalence data. BMI centiles matching BMI values at age 18 years, which are used for defining thinness, overweight and obesity in adults, were calculated. In Austria, using reference values as thresholds, ∼18% of boys and 12% of girls are overweight (with thresholds passing through BMI 25.00-29.99 kg/m(2) in adults) and 5% of boys and 3% of girls are obese (with thresholds passing through BMI ≥30.00 kg/m(2) in adults). CONCLUSION: Overweight and obesity are common in Austria and their prevalence is increasing (using the same IOTF reference for international comparison). Up-to-date national BMI reference values are provided to classify children and adolescents according to the proposed overweight and obesity thresholds.

Cystic fibrosis-related diabetes compared with type 1 and type 2 diabetes in adults.

BACKGROUND: With increasing life expectancy of patients with cystic fibrosis (CF), secondary diabetes becomes more prevalent. It appears to be the most common co-morbidity in persons with cystic fibrosis. Therefore, the objective of our study was to describe characteristics of cystic fibrosis-related diabetes compared with type 1 and 2 diabetes (T1DM/T2DM) in adults. METHODS: Data from 218 436 patients >18 years with cystic fibrosis (n = 401), T1DM (n = 32,409) or T2DM (n = 185 626) in the multicenter Diabetes-Patienten-Verlaufsdokumentation or prospective documentation of diabetes patients registry were analysed. RESULTS: Diabetes onset [median (interquartile range)] in cystic fibrosis [18.70 (15.50-25.30) years] was between T1DM [16.40 (10.50-31.80) years] and T2DM [58.50 (48.80-68.00) years], with female preponderance. Body mass index (BMI) and glycosylated haemoglobin (HbA1c ) were lowest (19.6 [18.1-21.5] kg/m(2) )/50 mmol/mol (6.73%) versus T1DM (24.4 [22.1-27.4])/62 mmol/mol (7.83%) vs. T2DM (29.6 [26.1-33.9])/54 mmol/mol (7.06%); all p < 0.01. A total of 78.6% of cystic fibrosis patients with diabetes received insulin. Insulin dose (0.74 IE/kg bodyweight) was not significantly different from T1DM (0.73) and T2DM (0.76). Frequency of vascular complications, adjusted for confounding effects, across the groups was different: Hypertension (CFRD 16.1% vs. T1DM 24.0% vs. T2DM 32.2%; all p < 0.01), retinopathy (CFRD 10.7% vs. T1DM 10.4% vs. T2DM 10.5%, not significant), nephropathy (CFRD 25.2% vs. T1DM 17.2% vs. T2DM 24.7%; only T1DM/T2DM; p < 0.01). CONCLUSION: CFRD is a uniquely complex entity with clear differences from T1DM and T2DM in adults.

Austrian height and body proportion references for children aged 4 to under 19 years.

BACKGROUND: Previous studies have demonstrated differences between national and the WHO reference curves in children older than 5 years. Moreover, reference curves for body proportions (sitting height, subischial leg length and their ratio) based on state-of-the-art statistics are not available. AIM: To develop reference curves for height and body proportions for use in Austria and compare the curves with WHO reference curves. To estimate and statistically investigate extreme percentiles. SUBJECTS AND METHODS: A sample of ∼14 500 children between 4-19 years of age was drawn via schooling institutions, stratified by provinces according to age- and sex-specific population proportions. GAMLSS models were used for a flexible estimation of percentile curves. RESULTS AND CONCLUSIONS: After the age of 5 years national reference curves are more suitable than the WHO reference curves for clinical use in Austria. These height curves are very similar to the German reference curves published recently. Therefore, these reference curves for criteria of body proportions are recommended for use in other populations. Further validation studies are needed to establish whether the recently recommended -2.5 and -3.0 SD for height are a sensitive and specific cut-off in the diagnostic work-up for children with a suspected growth disorder using this new Austrian height chart.

Prevalence of cardiovascular risk factors in children and adolescents with type 1 diabetes in Austria.

Mortality of cardiovascular diseases in patients with type 1 diabetes is increased 2- to 20-fold compared to non-diabetic individuals. In young adults with type 1 diabetes, cardiovascular events are more often the cause of premature death than nephropathy. The aim of this study was to evaluate the prevalence and extent of cardiovascular risk factors in children and adolescents with type 1 diabetes in Austria. In a cross sectional study data of children with type 1 diabetes <18 years of age treated at the Children's department of the University Hospitals of Vienna and Graz were collected. We recorded body mass index, waist circumference, blood pressure, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol according to age, sex, age at manifestation, diabetes duration, and insulin requirement. From 264 patients (49.4% male) complete data were available. Of all patients, 76.1% had one or more risk factors, 20.8% had two or more, 10.2% had three or more, and 4.9% had four or more risk factors. Insufficient glycemic control was the most frequent risk factor, present in 60.6% of our patients, followed by elevated triglycerides (22.7%) and increased body mass index (20.1%). Higher prevalence of risk factors was correlated with increasing age, diabetes duration, HbA1c, and insulin requirement. In conclusion, children and adolescents with type 1 diabetes have a much higher prevalence of cardiovascular risk factors compared to non-diabetic individuals. To prevent future cardiovascular events, achieving the best possible glycemic control, early detection of further risk factors, and adequate intervention are highly important.

Do children and adolescents with type 1 diabetes mellitus have a higher frequency of parietal cell antibodies than healthy controls?

OBJECTIVES: Parietal cell antibodies (PCA) are markers of autoimmune gastritis (AG). AG can lead to hypergastrinemia and iron-deficiency anaemia (IDA). Compared to healthy controls, adults with type 1 diabetes mellitus (T1DM) show a higher prevalence of PCA (1% vs 20%). The aim of the present study was to evaluate the frequency of PCA in children and adolescents with T1DM compared to healthy controls and the clinical and biochemical markers. PATIENTS AND METHODS: We studied 170 patients (87 boys) with T1DM (mean age 12.9 years) and 101 healthy controls (49 boys; mean age 13.0 years). PCA, free T4, free T3, thyroid-stimulating hormone (TSH), and thyroid antibodies were measured in all of the patients. In addition, gastrin, pepsinogen I, iron, ferritin, vitamin B12, and folate were measured in patients with T1DM only. Gastroscopy was carried out in patients with T1DM having high (>100 U/mL) PCA levels. RESULTS: The frequency of PCA in patients with T1DM was 5.29% compared to 1.98% in healthy controls (not significant). PCA was strongly correlated to both thyroid peroxidase antibodies (TPOAb) and gastrin levels (P = 0.001). IDA was present in 4 of 9 patients from the PCA-positive group compared to 4 of 160 patients from the PCA-negative group. Hypergastrinemia was found in 2 PCA-positive patients. Histopathologically, 1 of 4 patients showed early symptoms of AG. CONCLUSIONS: Children and adolescents with T1DM have a lower frequency of PCA than is reported for adults. Compared to healthy controls, they seem to be at increased risk for developing PCA, in particular if positive for TPOAb, but overt clinical disease is rare in children with T1DM.

The influence of physical activity on ghrelin and IGF-1/IGFBP-3 levels in children and adolescents with type 1 diabetes mellitus.

OBJECTIVES: The aim of the study was to determine the influence of regular physical activity on ghrelin and IGF-1/IGFBP-3 levels during a diabetes camp. METHODS: Twenty-eight children and adolescents (14 boys; mean age 12.1 yr) with type 1 diabetes mellitus (T1DM, mean duration of diabetes 4.8 yr) attending a 2-wk diabetes camp that features increased regular physical activities have been studied. Serum levels of ghrelin (total and acylated), growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor-bindng protein-3 (IGFBP-3) and insulin were measured in fasting state on day 1 and day 14. Improvement of metabolic control was documented by haemoglobin A1c (HbA1c). Glucose levels and insulin doses were determined daily. RESULTS: Mean insulin dosage decreased from 0.87 to 0.78 U/kg/d, mean HbA1c levels decreased from 8.6 to 8.3%, but the changes were not statistical. There was a significant decline in total ghrelin. IGFBP-3 and IGF-1 decreased also significantly. Total basal ghrelin was inversely related to the change in IGFBP-3. CONCLUSIONS: We hypothesize an association between ghrelin and metabolic control in T1DM. Higher ghrelin levels might be associated with poor metabolic control. The dynamic of IGFBP-3 levels appears to be under the influence of basal ghrelin concentrations in T1DM.

[Microvascular and macrovascular complications in children and adolescents with type 1 diabetes mellitus]. / Typ-1-Diabetes mellitus: Spätkomplikationen im Kindes- und Jugendalter.

Diabetes-related microvascular and macrovascular complications, as retinopathy, nephropathy and neuropathy are life-threatening complications in children and adolescents with type 1 diabetes mellitus (T1DM). Risk factors for the development of complications are longer duration of diabetes, older age and puberty. Further risk factors include smoking, hypertension, higher body mass index and dyslipoproteinaemia. Therefore prevention and screening for complications is an important part in the care of children and adolescents with T1DM. Target levels to reduce the risk of microvascular and macrovascular complications in children and adolescents with T1DM are the following: HbA1c<7.5%, lipids in normal range, blood pressure<90th percentile by age, sex and height, BMI<95th percentile, no smoking and physical activity. Screening for retinopathy and microalbuminuria should start from 11 years with two years diabetes duration and from 9 years with 5 years duration and after 2 years diabetes duration in an adolescent. Thereafter screening should be performed annually. Blood pressure should be measured at least annually. Screening for fasting blood lipids should be performed soon after diagnosis in all children with T1DM aged over 12 years. If normal results are obtained, this should be repeated every 5 years.

Estimated Glomerular Filtration Rates Calculated by New and Old Equations in Children and Adolescents With Type 1 Diabetes-What to Do With the Results?

Background: To apply and evaluate various equations for estimated glomerular filtration rates (eGFR) in a large paediatric type 1 diabetes population and compare the eGFR values with urinary creatinine clearances (UCC) in a subset of patients. Methods: Six eGFR formulae applicable for children and adolescents were used for calculation of eGFR values in 36,782 children/adolescents with type 1 diabetes. Via regression models, factors influencing eGFR values were identified. eGFR values were compared with measured UCC in 549 patients. Spearman correlation coefficients were given to assess the relation of eGFR and UCC values. Bland-Altman-Plots with corresponding linear regression were drawn to evaluate the agreement between eGFR and UCC. Results: eGFR values differed widely depending on the formula used, resulting in a percentage of pathological values <60 mL/min/1.73 m2 up to 8%. Regression models showed age, sex, and duration of diabetes as influencing factors. Microalbuminuria was associated with significantly higher eGFR values for all formulae. In comparison of eGFR with UCC, the highest correlation coefficient was 0.33, the lowest 0.01. Bland-Altman-Plots demonstrated graphically a poor agreement between eGFR and UCC, regardless of the formula used. Conclusions: The broad range of eGFR values indicate that an ideal eGFR formula for children and adolescence with T1D is yet missing. The minimal agreement between measured UCC and eGFR values urges us to be careful in application and interpretation of eGFR values regardless of the formula used.

Ghrelin--an indicator for fat oxidation in obese children and adolescents during a weight reduction program.

The aim of this study was to investigate the effect of short-term energy restriction combined with physical activity on changes in substrate oxidation and changes in plasma concentrations of ghrelin. We designed a longitudinal intervention study of 4.2 MJ (= 1,000 kcal) daily with exercise. Eighteen obese children and adolescents (age: 13.1 +/- 1.6 years, 13 girls, 5 boys, 17 White, 1 Black) participated. We measured body mass index (BMI), plasma ghrelin, resting energy expenditure (REE), VCO2, VO2 and respiratory quotient (RQ) at baseline and after 10 days. There was a significant decrease of BMI during the 10 day program (28.6 +/- 4.3 vs 27.5 +/- 4.2; p < 0.001). Ghrelin and RQ showed a tendency to increase, but the difference did not reach significance (ghrelin: 83.4 +/- 37.1 vs 99.5 +/- 41.2, p = 0067; RQ: 0.83 +/- 0.06 vs 0.85 +/- 0.08, p = 0.433). The changes in RQ were significantly and independently correlated with the changes in plasma ghrelin (p = 0.029). The increase in RQ suggests a shift from fat oxidation towards carbohydrate oxidation. Ghrelin reflects the same sensitivity as RQ to changes in energy balance. Therefore, ghrelin seems to be a sensitive indicator for changes in substrate oxidation.

Applicability of Greulich-Pyle and Tanner-Whitehouse grading methods to MRI when assessing hand bone age in forensic age estimation: A pilot study.

Determination of skeletal development is a key pillar in forensic age estimation of living persons. Radiological assessment of hand bone age is widely used until the age of about 17-18 years, applying visual grading techniques to hand radiographs. This study investigated whether Greulich-Pyle (GP) and Tanner-Whitehouse (TW2) grading can be equally used for magnetic resonance imaging (MRI) data, which would offer the huge benefit of avoiding ionizing radiation. In 18 subjects aged between 7 and 17 years a radiograph and an MRI scan of the hand were performed. Epiphyseal ossification of hand bones was rated by two blinded radiologists with both GP and TW2. Correlation between hand MRIs and radiographs was analyzed by linear regression and inter-observer agreement was assessed. Correlation between age estimates from MRI and radiographs was high for both GP (r(2)=0.98) and TW2 (r(2)=0.93). MRI showed a tendency to estimate age slightly lower for 14-18 year-olds, which would be favorable regarding majority age determination in case this result could be reproduced using a currently not existing reference estimation method based on MRI data. Inter-observer agreement was similar for GP in radiographs and MRI, while for TW2, agreement in MRI was lower than in radiographs. In spite of limitations regarding sample size and recruited subjects, our results indicate that the use of GP and TW2 on MRI data offers the possibility of hand bone age estimation without the need for ionizing radiation.

Only minor changes in thrombin generation of children and adolescents with type 1 diabetes mellitus - A case-control study.

BACKGROUND: Micro- and macrovascular diseases are frequent complications in patients with diabetes. Hypercoagulability may contribute to microvascular alterations. OBJECTIVE: In this study, we investigated whether type 1 diabetes in children is associated with a hypercoagulable state by performing a global function test of coagulation - the thrombin generation assay. SUBJECTS: 75 patients with type 1 diabetes aged between 2 and 19years were compared to an age-matched healthy control group. Diabetes patients were divided into high-dose and low-dose insulin cohorts with a cut-off at 0.8Ukg-1d-1. METHODS: Measurements were performed with platelet poor plasma using Calibrated Automated Thrombography and 1 pM or 5 pM tissue factor. Additionally, we quantified prothrombin fragments F1+2, thrombin-antithrombin complex, prothrombin, tissue factor pathway inhibitor, and antithrombin. RESULTS: Patients with type 1 diabetes exhibited a significantly shorter of lag time as well as decreased thrombin peak and endogenous thrombin potential compared to control subjects with 5 pM but not with 1 pM tissue factor. In high-dose insulin patients peak thrombin generation was higher and time to peak shorter than in low-dose patients. Thrombin-antithrombin complex was decreased in patients with type 1 diabetes, whereas prothrombin fragments F1+2 was comparable in both groups. Thrombin generation parameters did not correlate with parameters of metabolic control and the duration of diabetes. CONCLUSIONS: Taken together, we found only minor changes of thrombin generation in children and adolescents with type 1 diabetes which - in contrast to type 2 diabetes - do not argue for a hypercoagulable state.

Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin.

CONTEXT: There is growing evidence that adiponectin, the most abundant adipocytokine of adipose tissue cells, plays a crucial role in advanced atherosclerosis. OBJECTIVE: The objective of the study was to evaluate the role of adiponectin in early atherosclerosis. DESIGN: One hundred forty obese juveniles (mean age, 13.5 +/- 4.4 yr) and 100 age-matched, healthy, normal-weight controls from the STYrian Juvenile Obesity Study were investigated. We measured adipocytokines, inflammatory biomarkers, parameters of insulin resistance, and lipid subfractions. Intima-media thickness (IMT) of common carotid arteries was determined by ultrasonography. Furthermore, lipometric measurements were performed in obese juveniles to determine the topographic distribution of sc adipose tissue (SAT). RESULTS: Compared with controls, the group of obese juveniles exhibited a significantly increased IMT (P < 0.001) and elevated high-sensitive C-reactive protein (P < 0.001), indicating early stages of atherosclerosis. Serum levels of adiponectin were highly significantly negatively correlated with carotid IMT, even after controlling for common cardiovascular risk factors (P < 0.001; r = -0.34). Furthermore, adiponectin was positively correlated with high-density lipoprotein-free cholesterol and serum apolipoprotein-A1 and negatively with triglycerides, insulin resistance, uric acid, and serum transaminases. By a multiple regression analysis, adiponectin was shown to be the strongest predictive variable for carotid IMT. Finally, adiponectin was found positively correlated with SAT thickness of the rear and inner thigh in boys and negatively with the SAT thickness of the neck in girls. CONCLUSION: In summary, our study describes an influence of SAT topography on adiponectin serum levels and provides first evidence that incipient atherosclerosis is associated with low serum levels of this adipocytokine.

Leptin responses to insulin administration in children with short stature.

Abstract The aim of the study was to investigate the effect of standard insulin tolerance test on plasma leptin levels in children with idiopathic short stature (ISS) and in children with growth hormone deficiency (GHD). Furthermore, plasma leptin levels were analyzed with regard to age, body mass index (BMI), and plasma levels of human growth hormone and of insulin-like growth factor-1 (IGF-1). Sixty-three patients with a height below the third percentile, an age of 10.24 +/- 0.40 years and a BMI standard deviation score (SDS) of -0.78 +/- 0.13 (weight SDS -0.07 +/- 0.12; height SDS -2.39 +/- 0.10) were investigated (mean +/- SD). Based on responses to insulin tolerance test, the patients were classified as ISS (n = 49) or GHD (n = 14). Plasma leptin levels were significantly lower in all patients 60 minutes ( P < .001) and 120 minutes ( P < .001) after insulin administration. This effect was independent of GHD, and no difference in leptin decrease was found when comparing patients with ISS to those with GHD. A correlation was found when comparing plasma leptin levels of all patients to BMI SDS (r = 0.43; P < .001) and plasma IGF-1 levels (r = 0.31; P < .01). Furthermore, positive correlation was found when BMI SDS was compared to IGF-1 (r = 0.25; P < .05). In summary, we found that insulin administration in children with short stature decreases plasma leptin levels, equally in those with and without GHD.

Reduced forearm blood flow in children and adolescents with type 1 diabetes (measured by near-infrared spectroscopy).

OBJECTIVE: The aim of this study was to measure forearm blood flow (FBF) to detect any possible changes that might indicate vascular disorders in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: FBF was measured by near-infrared spectroscopy (NIRS), venous occlusion at rest, and after handgrip exercise. A total of 40 children and adolescents with type 1 diabetes and 40 healthy children and adolescents (6-18 years) were matched for age and sex for comparison. RESULTS: In the diabetic group (age 12.79 +/- 2.9 years, duration of diabetes 51.5 +/- 36 months), FBF at rest was significantly lower (1.39 +/- 0.76 ml x 100 g muscle(-1) x min(-1)) than in control subjects (age 12.66 +/- 2.9 years, FBF at rest 1.90 +/- 1.19 ml x 100 g muscle(-1) x min(-1)). After exercise, FBF increased significantly less in the diabetic group (0.70 +/- 0.82 ml. 100 g muscle(-1) x min(-1)) compared with the control subjects (1.15 +/- 1.05 ml. 100 g muscle(-1) x min(-1)). FBF at rest decreased with increasing age in both groups. The change in FBF after exercise was independent of age in the diabetic group and increased with increasing age in control subjects. FBF is reduced with impaired hyperemic response after exercise in children and adolescents with type 1 diabetes. CONCLUSIONS: These data suggest that vascular disorders in childhood are detectable noninvasively by NIRS.

Accuracy of blood glucose meters for self-monitoring affects glucose control and hypoglycemia rate in children and adolescents with type 1 diabetes.

AIMS/HYPOTHESIS: This study investigated the accuracy of blood glucose meters for self-monitoring and its influence on glycated hemoglobin (HbA1c) levels and the frequency of hypoglycemic coma. MATERIALS AND METHODS: Self-measured and simultaneously obtained laboratory blood glucose values from 9,163 patients with type 1 diabetes <18 years of age in the German/Austrian Diabetes Prospective Documentation Initiative registry were analyzed by investigating their compliance with the International Organization for Standardization (ISO) criteria (versions 2003 and 2013) and by error grid analyses. Regression models elucidated effects on glucose control and hypoglycemia rates. RESULTS: Depending on the respective subgroup (defined by sex, age, duration of diabetes, mode of insulin therapy), 78.7-94.7% of the self-monitoring of blood glucose (SMBG) values met the old and 79.7-88.6% met the new ISO criteria. In Clarke and Parkes error grid analyses, the percentages of SMBG values in Zone A ranged between 92.8% and 94.6% (Clarke) and between 92.2% and 95.0% (Parkes). The patient group with SMBG devices measuring "far too low" (compared with the laboratory-obtained glucose levels) presented with a higher HbA1c level than those measuring "far too high," "too high," "identical/almost identical," or "too low" (based on quintiles of deviation). Performing "far too high" was associated with the highest rate of hypoglycemic coma in comparison with the other deviation quintiles. CONCLUSIONS: This study showed that current SMBG devices fulfilled neither the previous nor the new ISO criteria. Large deviations of the SMBG values from the "true" glucose levels resulted in higher HbA1c levels and markedly increased rates of hypoglycemic events.

Relationship between different subcutaneous adipose tissue layers, fat mass, and leptin in response to short-term energy restriction in obese girls.

This study addresses whether the expected relationship of 15 specified subcutaneous adipose tissue layers (SAT layers) from 1-neck to 15-calf and body fat mass (FM) with leptin was influenced by a weight-loss program. In 30 obese girls (10 prepubertal, 15 pubertal, and 5 late/postpubertal) SAT layers were measured by means of the optical device Lipometer. Fat mass (FM) was estimated indirectly by means of bioelectrical impedance. Leptin and insulin were determined by means of radioimmunoassays. All measurements were performed before (pre) and after (post) 3 weeks of low-caloric diet and physical training. At the beginning of the study, there were significant correlations for all estimates of adiposity and leptin (0.67 to 0.79; P < 0.0001). Five SAT layers from the upper body and the trunk (0.48 to 0.67; P < 0.01) but none from the abdominal region and lower extremities were correlated with leptin. FM together with SAT layers 4-upper back and 8-lower abdomen (negative slope) explained 79% of the variation in pre leptin values (P < 0.0001). The weight-loss program significantly reduced leptin (P < 0.0001), insulin (P = 0.04), estimates of adiposity (P < 0.0001), and SAT layers 4-upper back (P = 0.0006), 11-front thigh, 13-rear thigh, and 14-inner thigh (P between <0.03 and <0.01). Although significant, the reductions in the four SAT layers were small. Estimated fat-free mass was significantly increased after three weeks (P < 0.05). Changes in SAT layers from the upper extremities and from the trunk were inversely correlated to the decrease in leptin (P between <0.05 and <0.001). Initial leptin was the best correlate of the decrease in leptin (adj. R(2) = 0.815; P < 0.0001). However, when only changes in adiposity and insulin were considered in the regression model, changes in insulin contributed to the fall in leptin (adj. R(2) = 0.23; P = 0.004). When changes in SAT layers were added to the model, changes in SAT layers 2-triceps and 10-hip (negative slopes) contributed to the decrease in leptin (adj. R(2) = 0.48; P < 0.0001). After weight loss, correlations between estimates of post adiposity and post leptin (0.40, P = 0.01 to 0.57, P = 0.0005) were lower compared with pre values. SAT layers 4-upper back and 3-biceps contributed independently to post leptin values (adj. R(2) = 0.50; P < 0.0001). It is suggested that fat mass and SAT layers from the upper body are the main determinants of leptin in obese girls before weight loss. The diet and sports intervention program reduced leptin independent of the reduction in adiposity. The distribution of subcutaneous fat might be a stable correlate of circulating leptin after a short-term reduction in energy intake. Am. J. Hum. Biol. 12:803-813, 2000. Copyright 2000 Wiley-Liss, Inc.

Rewarming index of the lower leg assessed by infrared thermography in adolescents with type 1 diabetes mellitus.

The aim of this study was to determine whether infrared thermography before and after challenge of the lower leg in cold water may be a useful tool to detect abnormalities in skin blood flow in adolescent asymptomatic patients with type 1 diabetes mellitus (DM1) and to assess the optimal setting of skin temperature measurements. Twenty-five adolescents (10 female, 15 male, mean age 21.2 +/- 6.2 years, body mass index [BMI] 23.0 +/- 2.1 kg/m2) with a duration of DMI of 13.8 +/- 5.4 years and mean HbA1c levels 8.5 +/- 1.3% were compared to age- and sex-matched controls (BMI 22.9 +/- 2.2 kg/m2). Seven defined sites of the lower leg were assessed by infrared thermography before and for 10 min after exposure of the leg to 14 degrees C cold water. As skin temperature before exposure to cold water differs from individual to individual and basal temperature was significantly warmer in patients at the tip of the first (p < 0.05) and fifth (p < 0.05) toe, the rewarming index was calculated in order to compare data. Rewarming indexes of skin temperature during the whole measurement procedure (0-10 min) were significantly lower at the tip of the first (p < 0.05) and fifth (p < 0.01) toes and from minute 2-10 also at the inner ankle (p < 0.05) in patients compared to healthy controls. Rewarming indexes of the other four sites were not significantly different between patients and controls. Infrared thermography of the lower leg after cold water exposure is an easily applicable method and a useful tool to detect abnormalities of skin blood flow in adolescents with DM1 especially at the tips of the first and fifth toes and the inner ankle.

Effects of TRH administration on plasma leptin levels in infants, children and adolescents.

The aim of this study was to investigate the effect of thyrotropin-releasing hormone (TRH) administration (standard TRH stimulation test) on plasma leptin levels in infants, children and adolescents. Plasma leptin levels were analyzed with regard to age, body mass index (BMI) and results in standard TRH stimulation test. The study population consisted of 79 infants, children and adolescents (age: 4.50 [0.04-20.49] years; BMI: 16.47 [12.46-38.32] kg/m2; BMI SDS: 0.21 [-2.97 to 3.26]) (median [range]). Plasma leptin levels significantly decreased 30 minutes after TRH administration (5 microg/kg; maximum 200 microg i.v.) (p <0.0001). No correlation was found in leptin decrease when comparing the different groups with regard to age, BMI and results in the TRH stimulation test. Positive correlation was found when comparing BMI SDS to plasma leptin levels before (r = 0.74; p <0.001) and 30 minutes after TRH injection (r = 0.73; p <0.001). There was poor correlation when age of patients was compared to plasma leptin levels before (r = 0.46; p <0.05) and 30 minutes after TRH injection (r = 0.47; p <0.05). In summary, we found that TRH administration decreases plasma leptin levels in infants and adolescents independent of age, BMI and thyroid function.