Analytical model of coincidence resolving time in TOF-PET.

The coincidence resolving time (CRT) of scintillation detectors is the parameter determining noise reduction in time-of-flight PET. We derive an analytical CRT model based on the statistical distribution of photons for two different prototype scintillators. For the first one, characterized by single exponential decay, CRT is proportional to the decay time and inversely proportional to the number of photons, with a square root dependence on the trigger level. For the second scintillator prototype, characterized by exponential rise and decay, CRT is proportional to the square root of the product of rise time and decay time divided by the doubled number of photons, and it is nearly independent of the trigger level. This theory is verified by measurements of scintillation time constants, light yield and CRT on scintillator sticks. Trapping effects are taken into account by defining an effective decay time. We show that in terms of signal-to-noise ratio, CRT is as important as patient dose, imaging time or PET system sensitivity. The noise reduction effect of better timing resolution is verified and visualized by Monte Carlo simulation of a NEMA image quality phantom.

Prevalence of overweight in children and adolescents with juvenile idiopathic arthritis.

OBJECTIVES: To assess the prevalence of overweight in patients with juvenile idiopathic arthritis (JIA) between 2003 and 2012 and to determine correlates of overweight relevant to the change in the overweight rate. METHOD: Annual overweight prevalence was determined in the National Paediatric Rheumatological Database (NPRD) between 2003 and 2012. The prevalence of overweight in JIA was compared to representative data from Germany in 2005. RESULTS: The median age of JIA patients was 11.5 years and the mean disease duration 4 years. Almost 50% of JIA patients had persistent oligoarthritis, followed by rheumatoid factor (RF)-negative polyarthritis (14%). The overweight prevalence decreased significantly from 14.2% in 2003 to 8.3% in 2012 [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.89-0.95]. Higher levels of physical activity and less frequent treatment with high-dose glucocorticoids (GCs) were associated with decreasing overweight rates. Systemic JIA had the highest decrease in the overweight rate over time. Patients with JIA had an overweight rate comparable to that of children and adolescents in the general population. However, systemic JIA and enthesitis-related arthritis were more likely to be associated with overweight. The use of high-dose GCs, lower functional limitations, and a lower level (or lack) of participation in school sports were significant predictors of overweight in multivariable analyses. CONCLUSIONS: The prevalence of overweight in JIA was comparable to the general population and decreased significantly over time. The decrease was associated with higher functional ability and JIA patients should be encouraged to be more physically active. The role of an elevated body mass index (BMI) in the long-term outcome of JIA needs to be addressed in future studies.

Treatment of young patients with HNF1A mutations (HNF1A-MODY).

AIM: Children and adolescents with a molecular diagnosis of HNF1A-MODY should be treated with oral sulfonylurea according to current International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines. METHODS: We surveyed the German-Austrian DPV database of 50 043 people and included 114 patients with a confirmed molecular-genetic diagnosis of HNF1A mutation and diabetes onset at below age 18 years. We analysed hypoglycaemic episodes, metabolic control (HbA1c ) and other clinical variables according to treatment groups. RESULTS: People with HNF1A-MODY were included and analysed according to treatment with insulin alone (n = 34), sulfonylurea (n = 30), meglitinides (n = 22) or lifestyle (n = 28). In those receiving any drug treatment (n = 86), severe hypoglycaemia did not occur with meglitinide and was highest (at 3.6 events per 100 patient-years) with insulin. HbA1c was highest with insulin treatment (insulin = 58 mmol/mol, 7.5%; sulfonylurea = 55 mmol/mol, 7.2%; meglitinides = 52 mmol/mol, 6.9%; P = 0.008), whereas weight (BMI SD score), serum lipids and blood pressure were not different. CONCLUSIONS: Of note, 40% of people with HNF1A-MODY and medical treatment were receiving insulin alone and thus were not being treated in line with up-to-date International Society for Pediatric and Adolescent Diabetes/International Diabetes Federation guidelines, despite insulin treatment being associated with worse metabolic control and the risk of hypoglycaemia. The unlicensed use of oral drugs in patients below age 18 years and adherence by both doctors and patients to the initial insulin treatment might contribute to this finding.

Results of the German ESPED-recording of new patients with juvenile dermatomyositis (JDM).

In a nation-wide registration project 38 incident cases of juvenile dermatomyositis were collected in Germany over a 2-year-period. Diagnostic methods as well as the primary treatment for these patients were recorded. Detailed information was available for 25 of these patients. Diagnostic as well as therapeutic decisions varied widely. Steroids were used in almost all of the 25 patients either as oral or as parenteral pulse therapy, additional immunosuppressive drugs were used in 52%. We plan to establish national consensus recommendations for diagnostic and therapeutic standards in JDM. Due to the rarity of JDM clinical trials will have to be performed on an international basis.

Genetic and clinical characteristics of patients with HNF1A gene variations from the German-Austrian DPV database.

OBJECTIVE: To determine prevalence, genetic and phenotype characteristics of patients with hepatocyte nuclear factor-1α (HNF1A) variants in the Diabetes Patienten Verlaufsdokumenation (DPV) multicentre database and to examine the influence of HNF1A mutation type, or location on clinical phenotypes. PATIENTS AND METHODS: Seventy-one DPV patients were labelled as HNF1A-MODY (MODY3). Forty-four patients carried HNF1A mutations, while 27 patients were found to have HNF1A polymorphisms only. Associations between mutation type/position and age at disease onset, HbAlc, body mass index (BMI), diagnosis, family history and treatment modality were analysed using non-parametric statistics (Wilcoxon test). RESULTS: Patients with HNF1A mutations were 36% male, aged 14.1±5.8 years at diagnosis, and slightly overweight (BMI-SDS: +0.8±1.1). Treatment was lifestyle intervention (20.5%), insulin (35.3%), oral anti-diabetic (OAD, 43%) and both insulin+OAD (15.9%). More patients with missense mutations (60%) than patients with nonsense mutations/frameshift (23.8%) did not use insulin (P=0.03). No differences were found with regard to mutation types, isoform or domain. We identified several previously undescribed mutations in the cohort including c.-158insGGGTTGG in the promoter region, G31X, E41X, Q130X, L162P, R245I, A269P, S355X, Q398X, Q473X, Q495X, E508X, P588fs-insGCCA and P588fs-delAC. Patients carrying HNF1A polymorphisms were significantly younger at diagnosis than patients with HNF1A mutations (10.9±4.2 vs 14.19±5.8 years; P=0.027), and all carried I27L, S487N and A98V (n=3). CONCLUSION: HNF1A-MODY is the second most frequent MODY diagnosis registered in the DPV database, and previously undescribed HNF1A mutations account for about one-third of HNF1A-MODY cases. Patients with HNF1A polymorphisms documented as HNF1A-MODY were misclassified. They may have autoantibody-negative type 1B or type 2 diabetes or may have other MODY types.

Entities and frequency of neonatal diabetes: data from the diabetes documentation and quality management system (DPV).

AIMS: The aim of this study was to elucidate the entities and the frequency of neonatal diabetes mellitus (NDM) in a large representative database for paediatric diabetes patients in Germany and Austria. METHODS: Based on the continuous diabetes data acquisition system for prospective surveillance (DPV), which includes 51,587 patients with onset of diabetes before the age of 18 years from 299 centres in Germany and Austria, we searched for patients with onset of diabetes mellitus in the first 6 months of life. RESULTS: Ninety patients were identified, comprising 0.17% of all paediatric cases in the DPV registry. This represented an incidence of approximately one case in 89,000 live births in Germany. A monogenic basis for NDM was established in 30 subjects (seven UPD6, 10 KCNJ11, seven ABCC8, two FOXP3, two PDX1, one INS, one EIF2AK3). Pancreatic hypoplasia or agenesis was reported in 10 patients and seven subjects were classified as having Type 1 diabetes by their centres. Transient neonatal diabetes (TNDM) accounted for approximately 10% of all cases with NDM. No aetiology was defined in 41 subjects, which may reflect incomplete genetic testing or novel genetic aetiologies. CONCLUSION: Based on a large database, we identified a higher rate of NDM in Germany than has been reported previously. Full molecular genetic testing should be performed in all patients diagnosed before 6 months of age.

Down's syndrome in diabetic patients aged <20 years: an analysis of metabolic status, glycaemic control and autoimmunity in comparison with type 1 diabetes.

AIMS/HYPOTHESIS: Intellectual impairment in individuals with Down's syndrome and diabetes mellitus potentially limits the quality of diabetic control. In addition, these patients are at risk of having immunological abnormalities. The present study compared metabolic status and concomitant diseases in young (<20 years old) Down's syndrome patients with diabetes vs young type 1 diabetic patients. METHODS: The Diabetes-Patienten-Verlaufsdaten is a longitudinal follow-up database, which collects data from 298 German and Austrian diabetes centres. Data available on diabetic patients aged <20 years were analysed statistically. RESULTS: We compared data for 159 Down's syndrome patients with diabetes and 41,983 type 1 diabetic patients. The former used less insulin, but showed better glycaemic control (HbA1c). Diabetes onset during the first 3 years of life occurred in 18.9% of Down's syndrome patients with diabetes and in 6.4% of type 1 diabetic patients. Antibody titres indicative of coeliac disease and thyroid peroxidase antibodies were more frequent in Down's syndrome patients with diabetes. No significant differences were found regarding the beta cell autoantibodies studied. CONCLUSIONS/INTERPRETATION: The age-of-onset distribution showed a shift towards younger ages and was bimodal in the Down's syndrome group. The better metabolic control found, despite intellectual impairment, in young Down's syndrome patients with diabetes cannot be conclusively explained by our data, but is likely to be due to a less complex lifestyle. Our data provide further confirmation that coeliac and thyroid antibodies are more prevalent in Down's syndrome. The presence of beta cell autoantibodies supports an autoimmune cause of diabetes in some children with Down's syndrome.

The economic burden of juvenile idiopathic arthritis-results from the German paediatric rheumatologic database.

OBJECTIVE: To estimate the cost of juvenile idiopathic arthritis (JIA) and to evaluate the influence of specific disease characteristics on the various costs domains. METHODS: Data on JIA outpatients (n=369) who were enrolled in the national paediatric rheumatologic database and completed a cost questionnaire were analysed. Direct JIA-related costs, families' out-of-pocket expenses and parents' income loss were calculated per patient and year, using physicians' reports, parents' 3-month recall, and average prices as the basis. RESULTS: The mean total cost of JIA was estimated to be 4,663 euro per patient per year. The highest costs were calculated for patients with seropositive polyarthritis and systemic arthritis (7,876 euro), and the lowest costs were seen for patients with persistent oligoarthritis (2,904 euro). Health-care costs accounted for 89% of total costs, and medication contributed to almost half of this value. A considerable amount of the cost was borne by the families, with a mean out-of-pocket cost of 223euro and a mean indirect cost due to time loss from work of 270 euros per year per family. Cost increased with disease activity and pain, disease duration, and time period from symptom onset to first paediatric rheumatologist visit; it also increased with the presence of uveitis. However, function, as measured by the Childhood Health Assessment Questionnaire, was the only factor significantly contributing to the variation in patient total costs. CONCLUSION: JIA imposes a significant economic burden. Medication (i.e. biologic drugs) contributes substantially to the total costs. However, these must be considered in the light of the patients' long-term outcomes.

Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database.

AIMS: To analyse and compare clinical characteristics in young patients with maturity-onset diabetes of the young (MODY) and Type 2 diabetes mellitus (T2DM). METHODS: We conducted an observational investigation using the DPV-Wiss database containing clinical data on 40 757 diabetic patients < 20 years of age from Germany and Austria. RESULTS: Three hundred and thirty-nine cases were clinically categorized as MODY (0.83%); 562 patients were diagnosed as T2DM (1.4%). In 20% of cases, the diagnosis of MODY was based on clinical findings only. Of the 272 subjects where genetic testing was available, 3% did not carry mutations in the three examined MODY genes. Glucokinase-MODY was commoner than HNF1A-MODY and HNF4A-MODY. Age at diagnosis was younger in MODY patients. The body mass index of T2DM was significantly higher compared with all MODY subgroups. Macrovascular risk factors such as dyslipidaemia and hypertension were commoner in T2DM, but 23% of MODY patients had dyslipidaemia and 10% hypertension. Glycaemic control was within the therapeutic target (HbA(1c) < 7.5%) in 86% of MODY and 70% of T2DM patients. CONCLUSIONS: The prevalence of MODY in children and adolescents in Germany and Austria is lower than that of T2DM in this age group. Dyslipidaemia and hypertension are less frequent in MODY compared with T2DM patients, but do occur.

Information needs in parents of children with a rheumatic disease.

BACKGROUND AND OBJECTIVE: Incorporating the patient's perspective and expectations into the delivery of health care has become an important indicator of today's quality of medical care. Our aim was consequently to explore the information needs of parents of children with juvenile idiopathic arthritis and other rheumatic diseases. MATERIALS AND METHODS: Cross-sectional, anonymous survey using a purpose-designed questionnaire, which separately assessed sources of information and topics. With respect to sources, we also asked about their degree of helpfulness, and regarding topics, we also asked about further interests (information needs). The questionnaire was sent to 146 families continuously attending our paediatric rheumatology outpatient clinic. The response rate was 79.5%. The mean age of the children was 6.9 +/- 4.3 years, 69% were girls and disease duration averaged 2.6 +/- 4.3 years. Mean Child Health Assessment Questionnaire score as a measure of functional disability was 0.259 (+/-0.45; range 0.0-2.13). RESULTS: Regarding sources, those with a professional medical background were appreciated, while information from friends and family members, in particular, was not. Overall, parents considered themselves well-informed. Parents had frequently received information on core domains of medical aspects. They described deficits related to psychosocial impact, to (vocational) education and to complementary therapy. However, their interest in further information was high almost irrespective of the amount of prior information. CONCLUSION: For further tailored information and support strategies it should be taken into account that even for topics largely covered by usual medical advice, residual interest and information needs of parents remain high.

Beta-cell autoantibodies in children with type 2 diabetes mellitus: subgroup or misclassification?

BACKGROUND: In adults, a fraction of diabetic individuals with beta-cell autoantibodies has initially non-insulin requiring diabetes clinically appearing as type 2 diabetes mellitus (T2DM), named latent autoimmune diabetes in adulthood (LADA). The occurrence of beta-cell autoantibodies in European children and adolescents with T2DM has not been reported so far. METHODS: The frequency of beta-cell autoantibodies (anti-GAD, anti-IA-2, and anti-ICA) was determined in 7050 diabetic children and adolescents. The type of diabetes was classified by paediatric diabetic specialists based on the clinical presentation. Children with non-insulin dependent T2DM over a one year period were studied separately. RESULTS: A total of 6922 children were clinically classified as having type 1 diabetes (T1DM) and 128 children as having T2DM. Thirty six per cent of the children with T2DM had at least one detectable beta-cell autoantibody. These children did not differ significantly from the children with T2DM and without autoantibodies in respect of age, gender, weight status, lipids, blood pressure, C-peptide, glucose, and HbA1c at manifestation, as well as frequency of anti-thyroidal antibodies and insulin treatment during follow up. In the subgroup of the 38 children with T2DM without insulin requirement over a one year period, autoantibodies occurred in 32%. These 12 children were predominantly obese (67%), female (67%), and in the pubertal age range. CONCLUSION: beta-cell autoantibodies were detectable in a subgroup of initially non-insulin dependent diabetic children and adolescents with the clinical appearance of T2DM. Following the terminology "latent autoimmune diabetes in adulthood (LADA)", this subgroup might be classified as "LADY" (latent autoimmune diabetes in youth).

[Epidemiology of uveitis in juvenile idiopathic arthritis from a national paediatric rheumatologic and ophthalmologic database]. / Epidemiologische Daten zur Uveitis bei juveniler idiopathischer Arthritis aus einer bundesweiten pädiatrischen und ophthalmologischen Datenerhebung (Uveitis-Modul der Kerndokumentation).

BACKGROUND: Uveitis is a frequent and potentially vision-threatening manifestation of juvenile idiopathic arthritis (JIA). There are only a few population-based studies providing data on the frequency and severity of uveitis. METHODS: Documentation of patients with JIA was collected in a national database. An analysis of the paediatric rheumatologic and ophthalmologic data collected from all patients that were included in 2002 was performed. RESULTS: Uveitis was documented in 12 % of a total of 3271 JIA patients: extended oligoarthritis (25 %), persistent oligoarthritis (16 %), seronegative polyarthritis (4 %), seropositive polyarthritis (2 %), psoriatic arthritis (10 %), enthesitis-related arthritis (ERA) (7 %), systemic arthritis (1 %), other arthritis forms (11 %). Ophthalmologic data were available from 115 uveitis patients (28 %). Mean age at onset of uveitis was 5.2 (SD 3.2) years. JIA patients with uveitis were significantly younger at onset of arthritis (3.8 vs. 7.0 years), and were more often girls (74 vs. 63 %) or ANA-positive (86 vs. 42 %) than the patients without uveitis. Uveitis complications were present in 45 % at initial presentation of uveitis. After a mean duration of 5.6 years, complications were noted in 56 %, and included band keratopathy (29 %), posterior synechiae (27 %), cataract (26 %), glaucoma (8 %), and macula oedema (6 %). Final visual acuity was less than 20/50 in 31 % and less than 20/200 in 12 % of eyes. In patients with uveitis, immunosuppressive or immunomodulatory drugs were used significantly more often than in patients without uveitis (75 % vs. 43 %). CONCLUSIONS: The nationwide data documents the spectrum of uveitis in patients with JIA, the complications and the therapy for uveitis. The high rate of uveitis complications at the time of diagnosis points out the need for early ophthalmologic screening and therapy, and for a close collaboration between ophthalmologist and paediatric rheumatologist.

The German etanercept registry for treatment of juvenile idiopathic arthritis.

OBJECTIVE: To describe a registry set up to monitor children treated with etanercept in Germany and Austria. METHODS: Giannini's criteria, duration of morning stiffness, number of swollen, tender and contracted joints, adverse events, and reasons for discontinuation were assessed. RESULTS: 322 patients with juvenile idiopathic arthritis (JIA) and 12 additional patients with non-JIA rheumatic diagnoses were included. Therapeutic efficacy was observed from one month after treatment was started. The number of patients with significant improvement and the degree of improvement increased during the first year. The mean (SD) number of tender and swollen joints decreased from 9 (9) and 8.4 (9) to 3.0 (6.5) and 4.5 (7) after one month, and to 2.2 (5.5) and 3.3 (5.5) after three months; morning stiffness decreased from 45 (65) minutes to 12 (30) and 7 (19) after one and three months (p<0.001 for all). Using Gianinni's criteria of 30%, 50%, and 70% improvement, a therapeutic response in JIA patients was achieved in, respectively, 66%, 54%, and 30% after one month, 78%, 61%, and 38% after three months, and 83%, 72%, and 52% after six months. Therapeutic efficacy was lower in patients with systemic onset arthritis. Overall tolerability was good: in 592 patient treatment-years there were 69 reports of adverse events in 56 patients, including one CNS demyelination. There were no opportunistic infections or lupus-like reactions. Treatment was discontinued in 53 JIA patients, in 25 because of lack of efficacy. CONCLUSION: Etanercept treatment was safe and led to a significant improvement in most JIA patients resistant to conventional treatment.

How do adolescents with juvenile chronic arthritis consider their disease related knowledge, their unmet service needs, and the attractiveness of various services?

AIMS: To explore the information needs of adolescents with juvenile chronic arthritis (JCA) with respect to patient education and other measures to promote self-management. METHODS: Standardized cross-sectional inquiry concerning disease-related knowledge, perceived importance of information giving, unmet needs as well as perceived attractiveness of a range of services (lecture, structured patient education, support group, self-help group) to promote self-management. SAMPLE: N = 48 adolescents (68% of all adolescents with JCA of our outpatient clinic); mean age x = 14.9 (+/- 2.1) years; 56% female; 17% had the oligoarthritis form of JCA, 40% juvenile spondylarthritis, 25% polyarthritis and systemic form, 19% other rheumatic diseases. RESULTS: The majority of adolescents considered themselves as sufficiently well-informed and voted in favour of detailed information giving. However, 30% were unsatisfied with their current information and knowledge. Information needs predominantly related to the prognosis, course, and treatment of JCA, whereas the psychosocial impact (except sports and job matters) were judged as less important. Adolescents with a lower level of education were generally more interested than those with a high level of education. As for the attractiveness of services nearly half of the adolescents judged all of them as not very attractive. CONCLUSIONS: The majority of adolescents is interested in detailed information giving and some of them point to unmet needs, but nearly half of them is hesitant towards services which are delivered in a group format (such as structured patient education or support groups).

Absence of spinal response to extracorporeal shock waves on the endogenous opioid systems in the rat.

Extracorporeal shock wave therapy (ESWT) seems to be a new therapeutic strategy for chronic pain due to tendopathies. Neurophysiological mechanisms of action for pain relief following ESWT are still unknown. The aim of this study was to investigate if the analgesic effect of ESWT is caused by modulation of the endogenous spinal opioid system. Rats were treated with two different energy flux densities (0.04 and 0.11mJ/mm(2)) and immunohistochemical analysis of met-enkephalin (MRGL) and dynorphin (Dyn) was performed at 4 or 72 h after ESWT. ESWT had no modulatory influence on the expression of the spinal opioid systems. Different energy doses or repetitive treatment did not alter MRGL or Dyn immunoreactivity in the spinal cord. Furthermore, a delayed effect of ESWT at 72 h after treatment was not detectable. We conclude from these findings that the analgesic effects of ESWT treatment are not supported by endogenous opioids.

[Value of exact focusing of extracorporeal shock waves (ESWT) in therapy of tendinitis calcarea. A prospective randomized study]. / Bedeutung der exakten Fokussierung extrakorporaler Stosswellen (ESWT) bei der Therapie der Tendinitis calcarea. Eine prospektive randomisierte Studie.

A controlled randomized study was designed to analyse the effect of extracorporeal shockwave therapy (ESWT) focussed on either the calcified region or the insertion of the supraspinatus tendon. The study included 50 patients who were treated with a Storz Minilith SI-1 prototype shockwave generator. In the treated group, 4000 impulses (ED+ 0.78 ml/mm2) were applied, under local anaesthesia to the insertion of the supraspinatus in 2 treatment sessions. Control patients received ESWT focussed on the calcified region. Follow-up examinations were carried out 12 weeks after treatment by an independent observer. We found functional improvement and pain reduction in both groups. Statistical analyses showed significant superiority of ESWT focussed on the calcified region for the parameters constant-score (primary endpoint, p < 0.001) and pain intensity (p = 0.001). For the treatment of calcific tendinitis affecting the supraspinatus, we recommend accurate fluoroscopy-controlled focussing of ESWT on the calcification. Focussing on the calcification rather than on the insertion of the supraspinatus tendon is significantly more effective. On the basis of our results, ESWT requires the use of suitable shockwave generators that permit accurate focussing.

Surface plasmon dynamics in silver nanoparticles studied by femtosecond time-resolved photoemission.

Multiphoton photoelectron spectroscopy reveals the multiple excitation of the surface plasmon in silver nanoparticles on graphite. Resonant excitation of the surface plasmon with 400 nm femtosecond radiation allows one to distinguish between photoemission from the nanoparticles and the substrate. Two different previously unobserved decay channels of the collective excitation have been identified, namely, decay into one or several single-particle excitations.

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.