Body mass index standard deviation score and obesity in children with type 1 diabetes in the Nordic countries. HbA1c and other predictors of increasing BMISDS.

BACKGROUND: Intensified insulin therapy may increase body weight and cause obesity. This study compared body mass index standard deviation score (BMISDS) and obesity rate in children with type 1 diabetes (T1D) in Denmark, Iceland, Norway and Sweden, and uncovered predictors for increasing BMISDS. METHODS: Data registered in the Nordic national childhood diabetes databases during the period 2008-2012 on children below 15 years with T1D for more than 3 months were compiled, including information on gender, age, diabetes duration, hemoglobin A1c (HbA1c ), insulin dose, severe hypoglycemia (SH), treatment modality, height and weight. The Swedish reference chart for BMI was used for calculating BMISDS. RESULTS: Totally, 11 025 children (48% females) (30 994 registrations) were included. Medians by the last recorded examination were: age, 13.5 years; diabetes duration, 4.3 years; HbA1c , 7.9% (63 mmol/mol); insulin dose, 0.8 IU/kg/d and BMISDS, 0.70. Obesity rate was 18.5%. Adjusted mean BMISDS (BMISDS adj) was inversely related to HbA1c and directly to diabetes duration. Higher BMISDS adj was found in those with an insulin dose above 0.6 IU/kg/d, and in girls above 10 years. Pump users had higher BMISDS adj than pen users, and patients with registered SH had higher BMISDS adj than patients without SH (both P < .001). CONCLUSION: Obesity rate in children with T1D in the Nordic countries is high, however, with country differences. Low HbA1c , long diabetes duration, higher insulin dose, pump treatment and experiencing a SH predicted higher BMISDS. Diabetes caregivers should balance the risk of obesity and the benefit of a very low HbA1c.

Diabetic ketoacidosis at the onset of type 1 diabetes is associated with future HbA1c levels.

AIMS/HYPOTHESIS: We investigated the long-term impact of diabetic ketoacidosis (DKA) at onset on metabolic regulation and residual beta cell function in a Danish population with type 1 diabetes. METHODS: The study is based on data from DanDiabKids, a Danish national diabetes register for children. The register provides clinical and biochemical data on patients with type 1 diabetes diagnosed in 1996-2009 and then followed-up until 1 January 2012. Repeated-measurement models were used as statistical methods. RESULTS: The study population comprised 2,964 children <18 years. The prevalence of DKA at diagnosis was 17.9%. Of the total subjects, 8.3% had mild, 7.9% had moderate and 1.7% had severe DKA. DKA (moderate and severe) was associated with increased HbA1c (%) levels (0.24; 95% CI 0.11, 0.36; p = 0.0003) and increased insulin dose-adjusted HbA1c (IDAA1c, 0.51; 95% CI 0.31, 0.70; p < 0.0001) during follow-up, after adjustment for covariates. Children without a family history of diabetes were more likely to present with DKA (19.2% vs 8.8%, p < 0.0001); however, these children had a lower HbA1c (%) level over time (-0.35; 95% CI -0.46, -0.24; p < 0.0001). Continuous subcutaneous insulin infusion (CSII) was associated with a long-term reduction in HbA1c, changing the effect of DKA, after adjustment for covariates (p < 0.0001). CONCLUSIONS/INTERPRETATION: DKA at diagnosis was associated with poor long-term metabolic regulation and residual beta cell function as assessed by HbA1c and IDAA1c, respectively; however, CSII treatment was associated with improvement in glycaemic regulation and residual beta cell function, changing the effect of DKA at onset in our population.

Left ventricular dysfunction in Klinefelter syndrome is associated to insulin resistance, abdominal adiposity and hypogonadism.

OBJECTIVE: Epidemiological data suggest there is an increased risk of dying from heart disease among patients with Klinefelter syndrome (KS). Due to high prevalence of hypogonadism and metabolic syndrome, we speculated that patients with KS may have subclinical changes in the left ventricular function. Therefore, the aim was to assess left ventricular long axis function by tissue Doppler echocardiography in patients with KS and relate these findings to the metabolic status and testosterone levels. DESIGN: Cross-sectional study. Out-patient clinic. PATIENTS: We investigated 25 unselected patients with KS, recruited from endocrine and fertility clinics. Twenty-five age-matched males served as controls. MEASUREMENTS: Left ventricular systolic long axis function (velocities and strain rate) assessed by tissue Doppler echocardiography related to free testosterone, fasting values of plasma glucose, insulin, homeostasis model assessment (HOMA)-index, cholesterol and triglycerides in addition to dual energy X-ray absorptiometry (DEXA) scan derived assessment of truncal body fat. RESULTS: The long axis function was significantly reduced in patients with KS (peak systolic velocities 4.4 +/- 1.3 vs. 5.3 +/- 1.0 cm/s, P < 0.01 and strain rate -1.3 +/- 0.3 vs.-1.6 +/- 0.3 s(-1), P < 0.01). However, the ventricular dysfunction was mainly attributed KS patients with metabolic syndrome. The peak systolic velocities were significantly correlated to truncal body fat (r = -0.72, P < 0.01) and free testosterone (r = 0.63, P < 0.01), but uncorrelated to plasma glucose, insulin and HOMA-index. CONCLUSION: Systolic long axis function is decreased in patients with KS and metabolic syndrome. The decrease in myocardial systolic function was significantly related to truncal body fat and hypogonadism, but not correlated to insulin sensitivity.

Incidence of severe hypoglycemia in children with type 1 diabetes in the Nordic countries in the period 2008-2012: association with hemoglobin A 1c and treatment modality.

OBJECTIVE: Treatment of type 1 diabetes has been intensified aiming at normalizing blood glucose, which may increase the risk of severe hypoglycemia (SH). We aimed to compare the incidence of SH events in the four Nordic countries Denmark, Iceland, Norway and Sweden, and to assess the influence of hemoglobin A1c (HbA1c) and treatment modalities on the frequency of SH; particularly, to explore if a HbA1c target ≤6.7% (50 mmol/mol) is feasible. RESEARCH DESIGN AND METHODS: Data on children below 15 years with a diabetes duration more than 1 year, registered in the national childhood diabetes databases in the four Nordic countries from 2008 to 2012, were compiled. Data completeness was more than 95%. RESULTS: Totally 8806 (48% females) patients with 29 715 person years were included, mean age and diabetes duration were 11 years and 5.1 years, respectively. The overall rate of SH was 6.0 per 100 patient-years, and did not change during the study period. The Swedish population constantly had the lowest SH incidence while it decreased significantly in the Danish population. HbA1c decreased significantly over time (p<0.01), while the number of pump users increased (p<0.01). Stratifying for HbA1c levels showed the lowest risk of SH in patients with HbA1c ≤6.7% (≤50 mmol/mol), but in the statistical models adjusting for possible confounders the difference between the HbA1c groups disappeared. Pump users had the lowest SH risk, also after adjusting for possible confounders. CONCLUSIONS: Risk of SH differs between the Nordic countries with the lowest risk in Sweden. Pump therapy was associated with decreased risk of SH. The low HbA1c group had the same or a lower risk of SH compared with the highest HbA1c groups. A target HbA1c ≤6.7% (≤50 mmol/mol) seems achievable without increasing the risk of SH.

Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children.

BACKGROUND/OBJECTIVES: Childhood obesity is a major health problem with serious long-term metabolic consequences. CD36 is important for the development of obesity-related complications among adults. We aimed to investigate circulating sCD36 during weight loss in childhood obesity and its associations with insulin resistance, dyslipidemia, hepatic fat accumulation and low-grade inflammation. SUBJECTS/METHODS: The impact of a 10-week weight loss camp for obese children (N=113) on plasma sCD36 and further after a 12-month follow-up (N=68) was investigated. Clinical and biochemical data were collected, and sCD36 was measured by an in-house assay. Liver fat was estimated by ultrasonography and insulin resistance by the homeostasis model assessment (HOMA-IR). RESULTS: Along with marked weight loss, sCD36 was reduced by 21% (P=0.0013) following lifestyle intervention, and individual sCD36 reductions were significantly associated with the corresponding decreases in HOMA-IR, triglycerides and total cholesterol. The largest sCD36 decrease occurred among children who reduced HOMA-IR and liver fat. After 12 months of follow-up, sCD36 was increased (P=0.014) and the metabolic improvements were largely lost. CONCLUSIONS: Weight-loss-induced sCD36 reduction, coincident with improved insulin resistance, circulating lipids and hepatic fat accumulation, proposes that sCD36 may be an early marker of long-term health risk associated with obesity-related complications.

The macrophage activation marker sCD163 is associated with changes in NAFLD and metabolic profile during lifestyle intervention in obese children.

BACKGROUND: Obesity is associated with metabolic derangement and non-alcoholic fatty liver disease (NAFLD). Macrophages are involved in liver inflammation and fibrosis, and soluble (s)CD163 is a macrophage activation marker. OBJECTIVES: To associate sCD163 with parameters of paediatric obesity and NAFLD, as well as changes in these parameters during lifestyle intervention. METHODS: We studied 117 obese children during a 10-week lifestyle intervention; 71 completed the 12-month follow-up. We recorded clinical and biochemical data, and performed liver ultrasonography. RESULTS: Baseline sCD163 was higher in children with elevated alanine transaminase (ALT) (2.3 ± 0.7 vs. 2.0 ± 0.6 mg L(-1), P = 0.03), steatosis (2.3 ± 0.7 vs. 2.0 ± 0.6 mg L(-1), P = 0.01) and high paediatric NAFLD fibrosis index (2.3 ± 0.7 vs. 1.9 ± 0.6 mg L(-1) , P = 0.03). Baseline sCD163 was independently associated with ALT, cholesterol and high-sensitivity C-reactive protein (hs-CRP). The change in sCD163 during lifestyle intervention was associated with changes in ALT, homeostatic model assessment of insulin resistance (HOMA-IR), hs-CRP and cholesterol, and inversely associated with the change in high-density lipoprotein cholesterol. CONCLUSION: sCD163 was associated with markers of liver injury and metabolic parameters in obese children, and changes in these parameters during lifestyle intervention. This may suggest that activated macrophages play a role in NAFLD and sCD163 may serve as a marker of liver disease severity and treatment effect.

Endocrine status in patients with optic nerve hypoplasia: relationship to midline central nervous system abnormalities and appearance of the hypothalamic-pituitary axis on magnetic resonance imaging.

We here: 1) describe the phenotypic spectrum, including magnetic resonance imaging (MRI) appearances of the pituitary stalk and anterior and posterior pituitary [H-P (hypothalamic-pituitary) axis], in children with optic nerve hypoplasia (ONH) with or without an abnormal septum pellucidum (SP); and 2) define endocrine dysfunction according to the MRI findings. Medical records of 55 children with ONH who had been assessed by ophthalmology and endocrine services were reviewed. All had MRI of the brain and H-P axis. Forty-nine percent of the ONH patients had an abnormal SP on MRI, and 64% had a H-P axis abnormality. Twenty-seven patients (49%) had endocrine dysfunction, and 23 of these had H-P axis abnormality. The frequency of endocrinopathy was higher in patients with an abnormal SP (56%) than a normal SP (39%). Patients were divided into four groups based on SP and H-P axis appearance: 1) both normal; 2) abnormal SP and normal H-P axis; 3) normal SP and abnormal H-P axis; and 4) both abnormal. The frequency of multiple pituitary hormone deficiency was highest (56%) in group 4, lower (35%) in group 3, and even lower (22%) in group 2. Precocious puberty was most common in group 2. None of the patients in group 1 had endocrine dysfunction. Thus, SP and H-P axis appearances on MRI can be used to predict the likely spectrum of endocrinopathy.

Bordetella pertussis diagnosed by polymerase chain reaction.

The object of this work was to test the polymerase chain reaction (PCR) for demonstration of Bordetella pertussis (BP) in nasopharyngeal secretions. The method was applied to patients with recently diagnosed pertussis, as verified by BP culture. In order to test the sensitivity and specificity of PCR for the diagnosis of BP, we used known concentrations of BP, Bordetella parapertussis and Bordetella bronchiseptica in aqueous solutions. PCR was furthermore carried out on species of bacteria that might be isolated from the nasopharynx. The applicability of PCR to patient specimens was tested in 25 patients in whose nasopharyngeal secretions BP had been demonstrated after 4-7 days of culture. The detection limit of PCR in aqueous solution was 1-2 BP bacteria per reaction tube. PCR was 100% specific for BP, showing no response with other Bordetella species or other bacteria known to colonize the nasopharynx. Of 25 patient specimens, 16 were PCR-positive 4-7 days after the positive primary culture had been established; only 5 out of 13 patient specimens were positive by repeated conventional nasopharyngeal culture at that time. We conclude that PCR is a possible alternative to culture for the demonstration of BP, as PCR is considerably faster than culture and might be more sensitive.

Respiratory tract infections in cytomegalovirus-excreting and nonexcreting infants.

BACKGROUND: There is evidence of an immunosuppressive effect of cytomegalovirus (CMV), and CMV has been claimed to be a copathogen in respiratory tract infections (RTI). We therefore studied the significance of CMV viral load in infants with RTI, compared the frequency of infection with respiratory viruses and followed the course of RTI in CMV-excreting vs. nonexcreting infants. METHODS: We examined 201 infants consecutively admitted to the Department of Pediatrics for RTI. At admission nasopharyngeal aspirates, throat swabs and urine were examined for CMV, and nasopharyngeal aspirates were examined for respiratory viruses. RESULTS: In these patients 23.3% had CMV in the urine, 15.3% had CMV in the throat and 10.9% had CMV in the nasopharynx; 26.2% excreted CMV in at least one site. No relationship was found between CMV viral load and clinical symptoms. Infection with respiratory viruses was as common in infants excreting CMV as in nonexcreting infants. Symptoms and the course of infection were not different in the two groups except that CMV-excreting infants had a significantly higher frequency of rhonchi at admission (P = 0.007) and a tendency for longer duration of cough (P = 0.06). CONCLUSION: CMV viral load was not related to clinical symptoms. The frequency of infection with common respiratory viruses in infants was independent of CMV excretion. The course of infection was not more complicated in infants excreting CMV; however, a higher frequency of rhonchi was demonstrated in patients with CMV.

Fractional gastrointestinal transit time: intra- and interindividual variation.

The intra- and interindividual variation in the gastrointestinal transit times was measured in 12 healthy adult test subjects using a scintigraphic method with 111In marked single unit tablets. Test conditions were semi-standardized. The variation within the same individual was as large as the variation between different subjects regarding the transit times through both the small and the large intestines. The small intestine transit time was 5 h (median) with an interquartile range of 4-7 h. The median transit time through the large intestine was 23.5 h (interquartile range 19.0-40.5 h). The coefficient of repeatability for the small intestinal and large intestinal transit time was 4 h and 33 h respectively. Our conclusion is that the 111In single unit capsule method can be used for measuring the fractional gastrointestinal transit times, but the intra- and interindividual variations are rather large and similar. From a radiation-hygienic point of view the 111In single unit capsule method is acceptable. The large inter- and intraindividual variation in gastrointestinal transit time might be an important factor in the absorption of certain drugs.

[Effects of antihypertensive agents on lipoproteins and thrombocyte function]. / Effekten af antihypertensiva på lipoproteiner og trombocytfunktion.

This article is a review of the literature concerning the effects of antihypertensive agents on the lipid status and thrombocyte function. Many investigations have revealed that thiazide diuretics, non-selective beta-blockers and beta-1 selective beta-blockers have resulted in alteration of lipids in a potentially atherogenic direction. Only thiazide diruetics have caused increase in low density lipoprotein, which is causally connected with increased tendency to atheroschlerosis. In some investigations, alpha-1 blockers have had a favourable effect on lipids in an atherogenic direction. Other antihypertensive agents appear, by and large, to be lipid neutral even although isolated investigations have demonstrated displacement of lipids both in positive and negative directions. Non-selective beta-blockers appear to alter thrombocyte function towards a greater tendency to aggregation while beta-1 selective beta-blockers are neutral. Ca-antagonists, angiotensin converting enzyme inhibitors and ketanserin have, theoretically, anti-aggregatory effects on the thrombocytes but only few ex vivo and in vivo experiments have confirmed this effect. Monitoring of lipids is recommended before and after antihypertensive treatment. Finally, the effect on thrombocyte function should be considered in the choice of hypertensive agent.

[Late endocrine and growth sequelae after cancer treatment in children]. / Endokrine og vaekstmaessige senfølger efter cancerbehandling af børn.

Growth and endocrinological disturbances are possible late side-effects of cancer treatment in childhood. These side-effects can be treated, thus their discovery is important. The side-effects particularly appear in the years following treatment with irradiation and/or alkylating chemotherapy. After irradiation of the brain or the neck the function of the thyroid and the parathyroid glands should be tested every third month the first year, and later on annually. Two years after the end of treatment, the patient should be examined for growth hormone deficiency. This examination should be carried out annually. One should be alert to symptoms of pubertas praecox the years prior to puberty. At the age when puberty is expected and thereafter one should look for signs of secondary hypogonadism. Primary hypogonadism may follow radiotherapy below the diaphragm and/or treatment with alkylating chemotherapeutics; further, reduced fertility in men and early menopause in women may follow these treatments. The bone structure of the face and the teeth may be damaged by radiation and chemotherapy, so therefore yearly examination by a dentist with specialty in this subject is recommended. Surgery in order to improve function may be a possibility.

[Hearing loss among premature and full-term infants in Rinköbing county. Results of tone and speech audiometry]. / Høretab blandt praemature og mature børn i Ringkøbing Amt. Tone- og taleaudiometrisk undersøgelse.

A material of 101 out of 111 premature infants admitted with gestational ages less than or equal to 35 weeks and birth weights less than or equal to 2,000 g to the Paediatric Department, Herning Central Hospital during the years 1977-1980 and 101 infants born at term and matched for age and sex were investigated with pure-tone audiometry in quiet surroundings and speech-audiometry in noisy surroundings in the Ringkøbing County Audiological Department in Holstebro. Where all frequencies were concerned, we found slightly more children from the premature group with hearing thresholds greater than 15 dB HL. One premature child had been equipped with a hearing aid (HA) at the age of 6 1/2 years on account of a hearing threshold in the best ear of 55 dB HL for all frequencies. Two children in the premature group had unrecognized hearing loss in the best ear between 30-40 dB HL for the average of the frequencies 500, 1,000 and 2,000 Hz. One of these children was equipped with a hearing aid. None of the children in the control group had hearing loss justifying a hearing aid. Good agreement was found between speech audiometry in noisy surroundings carried out with the Danish test material "Dantale" and pure-tone audiometry. In this group, speech-audiometry did not provide further information as compared with pure-tone audiometry. Although only few children with severe hearing defects were found, it is important that these are detected as soon as possible in view of their intellectual development. Premature infants constitute a risk group for defective hearing.

[Human herpesvirus 6. The etiological agent in exanthema subitum]. / Human herpesvirus 6. Det aetiologiske agens ved exanthema subitum.

Human Herpesvirus 6 (HHV-6) is the sixth human pathogenic Herpesvirus. It was isolated for the first time in 1986. The virus is isolated from blood and saliva and it is probable that it is latent in salivary glands and possibly also in blood. The most probable route of infection is droplet infection via saliva and thereafter possibly by blood. Sero-epidemiological investigations demonstrate that newly born infants are practically all passively immunised via maternal antibodies. At about the age of six months, HHV-6 antibody can be demonstrated in a minority of children. From the age of two years and until 50 years, HHV-6 antibody is present in 90-100% of the population. This is in agreement with the extensive HHV-6 infection in the age group from six months to two years. It is demonstrated that HHV-6 is the cause of exanthema subitum. It is uncertain whether HHV-6 is of pathogenetic significance for other diseases.

[Investigation for penicillin allergy among children]. / Undersøgelse for penicillinallergi hos børn.

During the period 1986-1991, 109 children were tested for penicillin allergy in the paediatric departments of Odense and Roskilde Hospitals. Determinations of specific IgE to penicillin (SIgEP) were performed on all of the children. Prick tests for penicillin were undertaken in the children i Odense only. All of the children who reacted negatively to SIgEP and the prick test were provoked by oral penicillin. Two children were SIgEP positive. One of these children was subsequently treated with penicillin without reaction. All of the prick tests were negative. One child reacted with an urticarial rash five hours after oral provocation. It is recommended that investigation for allergy to penicillin in children should be restricted to meticulous history taking and oral provocation with penicillin with equipment for treatment of anaphylaxis in readiness.

[Cerebral apoplexy in children]. / Apoplexia cerebri hos børn.

Stroke in children is rare. No really good studies of the incidence are available, an estimate, however, is 2-3/100,000 children per year. In this paper we discuss the pathophysiology and the many different causes of stroke in children. In many of the cases more than one prothrombotic condition exists. If the cause is not obvious an extensive programme of examinations is recommended. This is important not only in order to give the best individual treatment, but also necessary in order to decide whether the stroke has a genetic cause. Initially, the treatment is symptomatic, attaching importance to achieving good perfusion of the cerebrum and lowering the energy consumption of the cerebrum. The rational treatment might be prompt reperfusion by thrombolytic medicine: this regime has been tried in adults, but as yet no consensus about this treatment modality exists. In some cases causal treatment is possible. If the stroke has a genetic cause genetic consultation is important and prenatal investigations might be possible. Overall, the mortality in stroke in children is about 25%. About 25% will live without any sequelae and approximately 50% of the children will disabled to a greater or lesser extent.

[Metaphyseal chondrodysplasia as differential diagnosis to rickets]. / Metafysaer kondrodysplasi som differentialdiagnose til rakitis.

Metaphyseal chondrodysplasias are a heterogeneous group of rare disorders, with flaring and irregularity of various metaphyses. The radiographic changes are similar to rickets, but calcium and phosphorus metabolism is normal. Other types are Schmid, Spahr, McKusick, Schwachman and Jansen, which can be separated by clinical, radiographic, genetic and biochemical criteria. We present a patient with metaphyseal chondrodysplasia, Schmid type, whose bone disorder was thought to be rickets and was treated as such.

[The effects of nifedipine and captopril on blood pressure, clinical chemical parameters and general health]. / Nifedipins og captoprils effekt på blodtrykket, klinisk-kemiske parametre samt almenbefindendet.

The anti-hypertensive effects of slowly absorbable nifedipin in doses of 20-40 mg twice daily and 25-50 mg captopril twice daily were investigated in a randomized cross-over trial on 19 patients with slight to moderate hypertension. Both of these preparations caused significant reduction in the diastolic blood pressure (BT) measured two and 12 hours after the last dose. Nifedipin caused 5% reduction of the diastolic blood pressure measured 12 hours after the last dose more frequently than did captopril. Where both preparations were concerned, the blood pressure measured two hours after the last intake of medicine was significantly lower than after 12 hours. Neither of the two anti-hypertensive preparations resulted in changes in the clinical-chemical variables measured here. No changes in weight of over 5% were observed. Treatment with nifedipin frequently resulted in headache and flushing during the first days of treatment. Three of the patients did not wish to continue nifedipin treatment and one did not wish to continue captopril treatment after the period of observation. Six patients experienced considerably improved general health during captopril treatment and three during nifedipin as compared with their condition prior to treatment.

[Hereditary antithrombin deficiency resulting in severe neonatal thrombosis]. / Alvorlig neonatal trombose grundet hereditaer antitrombinmangel.

We report a severe vena cava inferior thrombosis in a mature two day-old boy. Pregnancy and birth were event free. The mother had antithrombin deficiency. During pregnancy she was treated with enoxaparin and just before delivery with 2000 IE antithrombin concentrate. At admission the child had unmeasurable antithrombin and low protein C concentrations. He was treated with antithrombin concentrate and heparin. The thrombus disappeared, and now he is on maintenance treatment with warfarin. Risk factors and treatment of inherited antithrombin deficiency are discussed.

[Pediatric evaluation of children with heart murmurs]. / Paediatrisk vurdering af børn med hjertemislyd.

In order to analyse the non-specialized paediatrician's ability to evaluate children with a heart murmur and the consequences of this evaluation for the need of further investigations, we made a prospective and consecutive study concerning 100 children who were referred for initial evaluation of a heart murmur. Based on the clinical evaluation, the children were assigned to one of the three categories of "no heart disease" "heart disease" or "definite heart disease". Within two months each child underwent a complete colour Doppler echocardiographic study. Except for one child with an insignificant peripheral pulmonary artery stenosis, 53% of the children were correctly diagnosed as having no heart disease. We conclude that clinical evaluation without laboratory tests performed by paediatricians without any special training in cardiology could correctly acquit half of the children of heart disease, with no need for further investigation.