Comparing effects of insulin analogues and human insulin on nocturnal glycaemia in hypoglycaemia-prone people with Type 1 diabetes.

AIMS: To assess the difference between analogue and human insulin with regard to nocturnal glucose profiles and risk of hypoglycaemia in people with recurrent severe hypoglycaemia. METHODS: A total of 72 people [46 men, mean ± sd age 54 ± 12 years, mean ± sd HbA1c 65 ± 12 mmol/mol (8.1 ± 1.1%), mean ± sd duration of diabetes 30 ± 14 years], who participated in a 2-year randomized, crossover trial of basal-bolus therapy with insulin detemir/insulin aspart or human NPH insulin/human regular insulin (the HypoAna trial) were studied for 2 nights during each treatment. Venous blood was drawn hourly during sleep. Primary endpoints were nocturnal glucose profiles and occurrence of hypoglycaemia (blood glucose ≤ 3.9 mmol/l). RESULTS: During insulin analogue treatment, the mean nocturnal plasma glucose level was significantly higher than during treatment with human insulin (10.6 vs 8.1 mmol/l). The fasting plasma glucose level was similar between the treatments. Nocturnal hypoglycaemia was registered during 41/101 nights (41%) in the human insulin arm and 19/117 nights (16%) in the insulin analogue arm, corresponding to a hazard ratio of 0.26 (95% CI 0.14 to 0.45; P < 0.0001) with insulin analogue. CONCLUSIONS: Treatment with insulin analogue reduces the occurrence of nocturnal hypoglycaemia assessed by nocturnal glucose profiles in people with Type 1 diabetes prone to severe hypoglycaemia. Nocturnal glucose profiles provide a more comprehensive assessment of clinical benefit of insulin regimens as compared to conventional recording of hypoglycaemia.

Effect of a school environment intervention on adolescent adiposity and physical fitness.

The aim of this study was to evaluate the effect of an intervention targeting the physical and organizational school environment for noncurricular physical activity (SPACE) on adiposity, aerobic fitness, and musculo-skeletal strength in Danish adolescents. The study used a cluster randomized controlled design. Fourteen schools and 1348 adolescents aged 11-14 years were included at baseline. Seven schools were randomized to the intervention, which was designed to change the organizational and physical environment of the school. The analysis revealed no significant differences between the adolescents in the intervention group compared to the comparison group after a 2-year follow-up. Adjusted for baseline, sex, age, and clustering within schools, the difference between the intervention schools compared to the comparison schools was 6 m in the shuttle run test [95% confidence interval (CI): -21; 33], 0.2 cm in waist circumference (95% CI: -2.6; 3.1), and -1.1 kg in handgrip strength (95% CI: -2.2; -0.1). The results did not provide evidence for the effect of the intervention on adiposity, aerobic fitness, or musculo-skeletal strength in adolescents. Reasons for not finding an effect could be related to both the design and the implementation of the intervention.

Skin temperature measured by infrared thermography after specific ultrasound-guided blocking of the musculocutaneous, radial, ulnar, and median nerves in the upper extremity.

BACKGROUND: Sympathetic block causes vasodilatation and increases in skin temperature (T(s)). However, the T(s) response after specific nerve blocking is unknown. In this study, we hypothesized that T(s) would increase after specific blocking of the nerve innervating that area. METHODS: Forty-six patients undergoing hand surgery were included. We performed ultrasound-guided, specific nerve blocking of either the musculocutaneous, radial, ulnar, or median nerve in each patient and analysed T(s) in the forearm and hand at 2 min intervals in the following 22 min by the use of infrared thermography. Areas of interest corresponding to the cutaneous innervation area of each of the four nerves were defined and the mean T(s) in each area was analysed. RESULTS: Specific blocking of the ulnar and median nerves caused a substantial increase in mean (sd) T(s) in the areas innervated by these nerves [5.2 (3.2)°C and 5.1 (2.5)°C, respectively; both P<0.0001]. The increase was even larger at the fingertips. Median nerve blocking also increased T(s) in the area of the hand innervated by the radial nerve (P<0.0001). However, T(s) did not increase in any area after either musculocutaneous or radial nerve blocking. CONCLUSIONS: Specific blocking of the ulnar and median nerve causes substantial increases in T(s) in specific areas of the hand. In contrast, the specific blocking of the musculocutaneous or radial nerve does not increase T(s). Further studies are needed to clarify if these findings can be used to objectively evaluate brachial plexus block success.

Secular trends in physical fitness in Danish adolescents.

It is important to monitor changes over time in aerobic fitness and obesity in order to target interventions when health deteriorates. We analyzed data from three population studies of adolescents carried out in 1983, 1997, and 2003. Participants were 1050 adolescents from the whole country of Denmark in 1983, 410 in 1997, and 418 in 2003, the two latter cohorts from the City of Odense. VO(2max) was estimated from maximal power output (MPO) in a cycle test with progressively increasing workload. Estimated VO(2max) for boys and girls was 52 and 41 mL/min/kg, respectively, both in 1983, 1997, and 2003 with no difference between the three cohorts. However, body mass index (BMI) increased 10% in the upper decentile of the distribution since 1983. MPO decreased over time, but validation studies showed that this was not due to decreased VO(2max) . The cohort from 1983 was tested twice by school teachers and experienced scientists, and the scientists found higher MPO than school teachers in the same subjects, which emphasize the importance of good validation studies.

Objectively measured habitual physical activity in 1997/1998 vs 2003/2004 in Danish children: the European Youth Heart Study.

Based on two cross-sectional studies conducted in 8-10-year-old third-grade children living in the municipality of Odense, potential differences were examined in the level of habitual physical activity (HPA) in Danish children between 1997/1998 and 2003/2004. HPA was assessed objectively by accelerometry. Primarily, overall differences were analyzed as gender and day type specific (i.e. Mon-Thu vs Fri-Sun) levels in HPA. Secondarily, differences were analyzed across socioeconomic gradients defined according to parents' occupation. Data were expressed as total counts per registered time. During the period 1997/1998-2003/2004, no significant differences were observed in the level of HPA during Mon-Thu or Fri-Sun or across socioeconomic gradients. Post hoc analyses indicated a slightly more favorable ratio between the percentages of time spent in light and moderate intensity levels during Mon-Thu in 2003/2004 when compared with 1997/1998. Gender differences in the level of HPA were found to be more distinct during Mon-Thu than during Fri-Sun. This study does not support the idea that Danish children are becoming less physically active. However, a limited statistical power should be considered when interpreting differences across socioeconomic gradients. Boys were found to be more physically active than girls, especially during the weekdays (Friday not included).

Varenicline may trigger severe hypoglycaemia in Type 1 diabetes.

BACKGROUND: Varenicline is a new drug indicated for smoking cessation. It has primarily been investigated in healthy adults. The commonest side-effects are nausea, headache, sleep disturbance, constipation, flatulence and vomiting. Hypoglycaemia has not been reported. As smoking cessation is important to reduce risk of cardiovascular morbidity, especially in diabetes, use of effective drugs indicated for smoking cessation is rational. CASE REPORT: We report multiple episodes of severe hypoglycaemia after starting varenicline in a 53-year-old woman with Type 1 diabetes. Since onset of diabetes at age 25 years and until start of varenicline therapy, she had only experienced one episode of severe hypoglycaemia and hypoglycaemia awareness was not impaired. The severe hypoglycaemic episodes disappeared after withdrawal of varenicline. CONCLUSIONS: We recommend cautious prescription of varenicline, intensified blood glucose monitoring and careful education of patients with diabetes treated with varenicline. Further investigation of the use of varenicline in patients with diabetes is warranted.

Effect of insulin analogues on frequency of non-severe hypoglycaemia in patients with type 1 diabetes prone to severe hypoglycaemia: The HypoAna trial.

AIM: Insulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night. METHODS: This 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal-bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996). RESULTS: Analogue-based treatment resulted in a 6% (2-10%; P=0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32-46%; P<0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36-57%]; P<0.0001) and asymptomatic (28% [14-39%]; P=0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months. CONCLUSION: In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with human insulin.

Insulin analogues and severe hypoglycaemia in type 1 diabetes.

INTRODUCTION: The effect of insulin analogues on glycaemic control is well-documented, whereas the effect on avoidance of severe hypoglycaemia remains tentative. We studied the frequency of severe hypoglycaemia in unselected patients with type 1 diabetes treated with insulin analogues, human insulin, or mixed regimens. METHODS: A questionnaire was posted from six Danish diabetes clinics to 6112 unselected patients with type 1 diabetes and filled in by 3861 patients (63.2%). Primary endpoint was number of episodes of severe hypoglycaemia in the preceding year. Mild hypoglycaemia was also reported. RESULTS: The frequency of severe hypoglycaemic episodes per patient-year in patients receiving long-acting insulin analogues was 1.47±0.18 versus 1.09±0.10 in patients on long-acting human insulin (p=0.01). The frequency of severe hypoglycaemic episodes per patient-year was 1.09±0.11 in patients on short-acting insulin analogues versus 1.26±0.13 in patients on short-acting human insulin (p=0.15), which was statistically significant in an adjusted analysis. CONCLUSIONS: Severe hypoglycaemia is more frequent in patients with type 1 diabetes treated with long-acting insulin analogues. Confounding by indication may be involved. Clinical intervention trials using insulin analogues in patients prone to severe hypoglycaemia are highly needed.

Hemodynamic variables during exercise in childhood and resting systolic blood pressure levels 6 years later in adolescence: the European Youth Heart Study.

The aim of this study was to analyze whether systolic blood pressure (SBP), heart rate (HR) and rate pressure product (RPP) during exercise in childhood can predict resting SBP levels in adolescence independent of resting SBP and conventional cardiovascular risk factors. We studied this in a sample of Danish children followed longitudinally for 6 years. The study comprised 226 children randomly sampled at age 9, who had their blood pressure and HR measured during ergometer exercise to exhaustion and was reassessed in adolescence. SBP and RPP during exercise in stage two of the test were positively associated with future resting SBP, independent of resting SBP in childhood (P=0.045 and P=0.013, respectively). After additional adjustment for conventional cardiovascular risk factors the associations with SBP and RPP during stage two on future resting SBP only slightly materially change, although only RPP remained significant (P=0.059 and P=0.012, respectively). No significant independent associations were observed for HR during exercise, but associations were in the same direction. Our results supports that measuring SBP and RPP, during a standard acute ergometer exercise test in children, improves the prediction of future SBP levels during rest in adolescence independent of resting SBP and conventional cardiovascular risk factors.

Erythropoietin and vascular endothelial growth factor as risk markers for severe hypoglycaemia in type 1 diabetes.

OBJECTIVE: Circulating erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increase during hypoglycaemia and may represent protective hormonal counter-regulatory responses. We tested the hypothesis that low levels of EPO and VEGF are associated with a higher frequency of severe hypoglycaemia in a cohort of patients with type 1 diabetes. DESIGN: Prospective observational follow-up study. METHODS: Totally 219 patients with type 1 diabetes (41% females, age 46+/-13 years (mean+/-s.d.), duration of diabetes 21+/-12 years, and HbAlc 8.5+/-1.1%) were followed in a 1-year observational study. Plasma EPO and serum VEGF levels were measured at baseline with ELISA. Events of severe hypoglycaemia defined by third party assistance were recorded and validated in telephone interviews within 24 h. RESULTS: Totally 235 episodes of severe hypoglycaemia (1.1 episodes per patient-year) were reported by 82 patients (37%). At baseline, plasma EPO was 8.6 (3.1-34.3) U/l (median (range)), and serum VEGF was 52.2 (6.6-337) pg/ml. The levels of EPO and VEGF were not associated with frequency of severe and mild hypoglycaemia. The levels of EPO were not associated with age, sex, duration of diabetes, body mass index, HbAlc, C-peptide level or hypoglycaemia awareness status. The levels of VEGF were positively associated with age and female sex. CONCLUSIONS: Although several studies suggest that VEGF and EPO may affect brain function during hypoglycaemia, this study does not support random VEGF or EPO levels to determine future risk of severe hypoglycaemia in people with type 1 diabetes.

Sources of variation in habitual physical activity of children and adolescents: the European youth heart study.

The present study examined the influence of gender, maturity state, seasonality, type of measurement day and socioeconomic status (SES) on habitual physical activity in 8-10-year-old children and 14-16-year-old adolescents (n=1318). Physical activity was assessed objectively by accelerometry. The results showed a significant effect of the type of measurement day on physical activity with a general pattern of lower activity levels in weekends compared with weekdays. Furthermore, higher physical activity levels were observed during the months of spring/summer compared with the months of autumn/winter for the 8-10-year-olds, whereas no significant effect of months was observed for the 14-16-year-olds, possibly due to exam preparations and lack of physical activity registration during the months of summer for this cohort. SES was unrelated to physical activity in the 8-10-year-olds, whereas an inverse association was observed in the 14-16-year-olds. However, a post hoc analysis provided strong evidence that this latter result was biased by the accelerometers inability to pick up bicycling activities. Finally, boys were more physically active compared with girls, and maturity state was unrelated to physical activity. The results could prove useful for working out strategies to prevent inactivity and for adjusting for temporal sources of variation in physical activity in future studies.

Tracking of objectively measured physical activity from childhood to adolescence: the European youth heart study.

A number of studies have investigated tracking of physical activity from childhood to adolescence and, in general, these studies have been based on methods with some degree of subjectivity (e.g., questionnaires). The aim of the present study was to evaluate tracking of physical activity from childhood to adolescence using accelerometry, taking into account major sources of variation in physical activity. Both a crude and an adjusted model was fitted, and, in the adjusted model, analyses were corrected for seasonal variation, within-week variation, activity registration during night time sleep, within instrumental measurement error, and day-to-day variation in physical activity. In all, 208 subjects were included in the crude analyses. Stability coefficients estimated from the crude model were low (i.e., 0.18 and 0.19 for boys and girls, respectively) and only borderline significant. However, in the adjusted model highly significant stability coefficients of 0.53 and 0.48 for boys and girls, respectively, were observed. It was concluded that physical activity behavior tends to track moderately from childhood to adolescence.

Secular trends in cardiorespiratory fitness and body mass index in Danish children: The European Youth Heart Study.

AIM: To examine the secular trends in cardiorespiratory fitness (CF) and body fatness in Danish children. Trends were analyzed overall and across socioeconomic status (SES). METHODS: Two cross-sectional studies conducted on 589 and 458 third-grade Danish children in 1997-1998 and 2003-2004, respectively. CF was determined by a maximal cycle-ergometer test. The lowest sex-specific quartile of CF in the study from 1997 to 1998 was used as a cut-point for low CF. Body mass index (BMI) cut-points were used to describe overweight, and SES was divided into two groups according to parents' occupation. RESULTS: This study showed a secular decline in CF in girls overall. Increased CF, BMI, and prevalence of overweight were observed in boys with high SES, in boys with low SES, and in girls with low SES, respectively. However, after additional Bonferroni's correction, none of the statistical analyses performed across socioeconomic gradients reached significant P-values. CONCLUSION: CF declined in girls overall. Although not statistically significant after additional Bonferroni's correction, results in general showed less favorable trends in low SES children. Thus, trying to describe secular trends in CF and body fatness overall without any regard to SES might disguise social-caused differences. However, further studies are needed in order to verify this hypothesis.