Increased mortality in a Danish cohort of young people with Type 1 diabetes mellitus followed for 24 years.

AIM: To determine the mortality rate in a Danish cohort of children and adolescents diagnosed with Type 1 diabetes mellitus compared with the general population. METHODS: In 1987 and 1989 we included 884 children and 1020 adolescents aged 20 years and under, corresponding to 75% of all Danish children and adolescents with Type 1 diabetes, in two nationwide studies in Denmark. Those who had participated in both investigations (n = 720) were followed until 1 January 2014, using the Danish Civil Registration System on death certificates and emigration. We derived the expected number of deaths in the cohort, using population data values from Statistics Denmark to calculate the standardized mortality ratio. Survival analysis was performed using Cox proportional hazards model. RESULTS: During the 24 years of follow-up, 49 (6.8%) patients died, resulting in a standardized mortality ratio of 4.8 (95% confidence interval 3.5, 6.2) compared with the age-standardized general population. A 1% increase in baseline HbA1c (1989), available in 718 of 720 patients, was associated with all-cause mortality (hazard ratio = 1.38; 95% confidence interval 1.2, 1.6; P < 0.0001). Type 1 diabetes with multiple complications was the most common reported cause of death (36.7%). CONCLUSION: We found an increased mortality rate in this cohort of children and adolescents with Type 1 diabetes compared with the general population. The only predictor for increased risk of death up to 24 years after inclusion was the HbA1c level in 1989. This emphasizes the importance of achieving optimal metabolic control in young people with Type 1 diabetes.

Retinal vascular geometry and its association to microvascular complications in patients with type 1 diabetes: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).

PURPOSE: To examine associations between retinal vascular geometry (tortuosity, branching coefficient [BC] and length-diameter ratio [LDR]) and diabetic proliferative retinopathy (PDR), nephropathy, and peripheral neuropathy in patients with type 1 diabetes mellitus (T1DM). METHODS: A cohort of patients with T1DM participated in a clinical examination in 2011. Blood and urine analyses were done and retinal images taken. PDR was defined as Early Treatment Diabetic Retinopathy Study level 61 or above, nephropathy as albumin-creatinin ratio ≥300 mg/g, and neuropathy as vibration perception threshold >25 Volt. Retinal vessel parameters were measured using semi-automated software. Multiple logistic regressions were performed to investigate correlations between retinal vascular parameters and outcomes. Models were adjusted for other variables (sex, age, duration of diabetes, systolic and diastolic blood pressure, HbA1c, and presence of microvascular complications). Odds ratios were given per standard deviation in retinal vascular parameter. RESULTS: Retinal vascular analyses were performed in 181 patients. Mean age and duration of diabetes were 37.0 years and 29.4 years respectively, and 50.8% were male. Prevalence of PDR, nephropathy, and neuropathy were 26.5%, 6.8%, and 10.1% , respectively. Patients with increased arteriolar BC had a higher risk of nephropathy (OR: 3.10, 95% CI: [1.01-9.54]). Patients with increased venular BC had a higher risk of neuropathy (OR: 2.11, 95% CI: [1.11-4.03]). No associations were found in patients with PDR. CONCLUSIONS: By analyzing the retinal vascular tree in patients with T1DM, we found a higher risk of complications in kidneys and nerves when BC was increased. This might indicate a suboptimal construction of the vascular tree in these patients.

Optimum bolus wizard settings in insulin pumps in children with Type 1 diabetes.

AIM: To evaluate current insulin pump settings in an optimally regulated paediatric population using bolus wizard. METHODS: We used a retrospective study design to analyse data from 124 children on insulin pump therapy who had optimum HbA1c levels [< 59 mmol/mol (< 7.5%)] and no history of severe hypoglycaemic events. Bolus wizard settings were used to calculate the insulin to carbohydrate factors and insulin sensitivity factors. Multiple regression analysis was used to analyse the variables associated with the calculation factors. RESULTS: Insulin to carbohydrate factor varied from 276 in the youngest group to 424 in the oldest group, and increased according to age. Insulin sensitivity factor was highest in the group aged 6 to < 12 years, with a value of 125. Age, amount of carbohydrates, number of boluses per day and insulin per kg were all significantly associated with both calculation factors. Furthermore, duration of insulin pump treatment was significantly associated with insulin sensitivity factor and percentage bolus/basal was significantly associated with insulin to carbohydrate factor. Gender, diabetes duration and BMI were not associated with any of the calculation factors. CONCLUSION: Optimum insulin pump settings at pump initiation depend on both insulin requirements and use of the pump. Settings need to be individualized because the standardized calculation factors are not constant for children. There is a need to develop specific age- and insulin dose-dependent calculation factors.

Long-term incidence of vitrectomy and associated risk factors in young Danish patients with Type 1 diabetes: the Danish Cohort of Paediatric Diabetes 1987.

AIMS: To examine the long-term incidence of vitrectomy in young people with Type 1 diabetes. METHODS: We prospectively studied 324 people with Type 1 diabetes who participated in baseline examinations in 1995. Surgical history was obtained from the Danish National Patient Registry in April 2012. RESULTS: During the 17-year study period, 39 people (12.0%) underwent vitrectomy at least once. The mean age and diabetes duration at first vitrectomy were 29.8 and 22.9 years, respectively, and 64.1% of the participants were men. In multivariable Cox regression analysis, baseline age (hazard ratio 0.81 per 1 year increase), BMI (hazard ratio 1.21 per 1 kg/m(2) increase), HbA1c (hazard ratio 1.72 per 1% increase) and diabetic retinopathy (hazard ratio 2.85 and 6.07 for mild and moderate/severe diabetic retinopathy vs none, respectively) were independent predictors of vitrectomy (P < 0.05 for all variables). CONCLUSIONS: Vitrectomy is a relatively common procedure in young people with Type 1 diabetes, with poor glycaemic control being the strongest modifiable risk factor.

Nationwide reduction in the frequency of severe hypoglycemia by half.

AIMS: To examine contemporary rates of severe hypoglycemia (SH) and identify the effect of predictors of SH in a pediatric type 1 diabetes population. METHODS: The national diabetes register provided data on children residing in Denmark from 2008 to 2013 in this register-based population study. Robust Poisson regression models were applied. RESULTS: The study population [n = 2,715 (50.9 % boys), mean (SD) age at onset; 8.1 (4.0) years, diabetes duration; 5.6 (4.9) years] comprised 7,390 person-years of data and 561 events of SH. The overall incidence of SH was 7.6 per 100 person-years. The incidence rate peaked with 16.0 per 100 person-years in 2008 reaching a nadir of 4.9 in 2011. Overall, insulin pump reduced the rate of SH with 27 % compared to any pen treatment (P = 0.003). When stratifying pen treatment, premixed insulin increased the rate of SH by 1.9-fold (P = 0.0015) and NPH increased the rate by 1.6-fold (P = 0.003) versus pump treatment, whereas long-acting insulin analogues were comparable with pump treatment (P = 0.1485). We found no association of SH with glycemic control (P > 0.05). CONCLUSIONS: A nationwide halving in rates of severe hypoglycemia was observed during the study period independent of the prevailing average HbA1c level. Changes in diabetes care and successful educational programs may have influenced the lower incidence rate of severe hypoglycemia.

Microaneurysm count as a predictor of long-term progression in diabetic retinopathy in young patients with type 1 diabetes: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).

PURPOSE: To investigate microaneurysm (MA) count as a predictor of long-term progression of diabetic retinopathy (DR) in young patients with type 1 diabetes mellitus (T1DM). METHODS: We examined 185 patients with T1DM at baseline (1995) and at follow-up (2011). At baseline, mean age and duration of diabetes were 20.6 and 12.9 years, respectively. Two-field (1995) and seven-field (2011) fundus photographs were taken in accordance with the European Diabetes Study Group (EURODIAB) and the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, respectively. DR was graded in accordance to the ETDRS protocol, allowing for non-standard photography at baseline. Baseline MAs were counted; patients without DR and those with MAs only were included. Multivariable logistic regressions were performed to investigate MA-count as a predictor of two-step progression, progression to proliferative DR (PDR), and incident diabetic macula edema (DME). RESULTS: We included 138 patients (138 eyes). Of these, 58 had no retinopathy and 80 had MAs only. At follow-up, rates of two-step progression of DR, progression to PDR and incident DME were 52.9, 21.7, and 10.1 %, respectively. In logistic regression models, MA count was able to predict progression to PDR (OR: 1.51 per MA; 95 % CI: [1.04-2.20]) and DME (OR: 1.69 per MA; 95 % CI: [1.05-2.77]), but not two-step progression (OR 0.91 per MA, 95 % CI: [0.64-1.31]). CONCLUSIONS: In younger patients with T1DM, MA count predicts long-term incidence of PDR and DME. This demonstrates that early DR is a warning sign of late retinopathy complications and that the number of MAs is an important factor for long-term outcome.

Outcome, revision rate and indication for revision following resurfacing hemiarthroplasty for osteoarthritis of the shoulder: 837 operations reported to the Danish Shoulder Arthroplasty Registry.

In this study, we evaluated patient-reported outcomes, the rate of revision and the indications for revision following resurfacing hemiarthroplasty of the shoulder in patients with osteoarthritis. All patients with osteoarthritis who underwent primary resurfacing hemiarthroplasty and reported to the Danish Shoulder Arthroplasty Registry (DSR), between January 2006 and December 2010 were included. There were 772 patients (837 arthroplasties) in the study. The Western Ontario Osteoarthritis of the Shoulder (WOOS) index was used to evaluate patient-reported outcome 12 months (10 to 14) post-operatively. The rates of revision were calculated from the revisions reported to the DSR up to December 2011 and by checking deaths with the Danish National Register of Persons. A complete questionnaire was returned by 688 patients (82.2%). The mean WOOS was 67 (0 to 100). A total of 63 hemiarthroplasties (7.5%) required revision; the cumulative five-year rate of revision was 9.9%. Patients aged < 55 years had a statistically significant inferior WOOS score, which exceeded the minimal clinically important difference, compared with older patients (mean difference 14.2 (8.8; 95% CI 19.6; p < 0.001), but with no increased risk of revision. There was no significant difference in the mean WOOS or the risk of revision between designs of resurfacing hemiarthroplasty.

The clinical outcomes of mosaicplasty in the treatment of osteochondritis dissecans of the distal humeral capitellum of young athletes.

BACKGROUND: The purpose of this study was to evaluate the clinical outcomes of mosaicplasty in the treatment of osteochondritis dissecans of the distal humeral capitellum. MATERIALS AND METHODS: Between 2003 and 2007, 10 patients (6 female and 4 male patients), with a mean age at surgery of 18 years (range, 13 to 27 years), with advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. The surgical technique involves transplanting small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyle at the level of the patellofemoral joint to the defect of the capitellum. At a mean follow-up of 30 months, all elbows were assessed with the Mayo Elbow Performance Score and a modified functional elbow score (Constant). RESULTS: Postoperative radiographs and control magnetic resonance imaging/computed tomography images showed incorporation of the subchondral cortex in all patients. All but 2 patients were completely pain free after surgery. Of the patients, 8 (80%) had no reduction in range of motion. By use of the Mayo Elbow Performance Score, the injured elbow had a preoperative mean score of 71 points (range, 55 to 85 points) and increased significantly to a mean score of 93.5 points (range, 85 to 100 points) postoperatively (P = .0005, paired t test). The nonoperative elbows had a mean score of 100 points, whereas the operated elbows had a mean score of 93.5 points. The functional elbow score showed a mean difference of 7.5 points between the operated and nonoperative elbows. No infection or neurologic deficit developed after surgery in any case. CONCLUSIONS: Autologous osteochondral mosaicplasty for advanced lesions of capitellar osteochondritis dissecans can provide satisfactory clinical and radiographic results.

Laxity of the elbow after experimental excision of the radial head and division of the medial collateral ligament. Efficacy of ligament repair and radial head prosthetic replacement: a cadaver study.

We studied the stabilising effect of prosthetic replacement of the radial head and repair of the medial collateral ligament (MCL) after excision of the radial head and section of the MCL in five cadaver elbows. Division of the MCL increased valgus angulation (mean 3.9 +/- 1.5 degrees) and internal rotatory laxity (mean 5.3 +/- 2.0 degrees). Subsequent excision of the radial head allowed additional valgus (mean 11.1 +/- 7.3 degrees) and internal rotatory laxity (mean 5.7 +/- 3.9 degrees). Isolated replacement of the radial head reduced valgus laxity to the level before excision of the head, while internal rotatory laxity was still greater (2.8 +/- 2.1 degrees). Isolated repair of the MCL corrected internal rotatory laxity, but a slight increase in valgus laxity remained (mean 0.7 +/- 0.6 degrees). Combined replacement of the head and repair of the MCL restored stability completely. We conclude that the radial head is a constraint secondary to the MCL for both valgus displacement and internal rotation. Isolated repair of the ligament is superior to isolated prosthetic replacement and may be sufficient to restore valgus and internal rotatory stability after excision of the radial head in MCL-deficient elbows.

The treatment of recurrent posterolateral instability of the elbow.

This study describes the surgical technique used for reconstruction and reinforcement of the lateral collateral ligament complex in patients with posterolateral instability of the elbow and the results. A triceps tendon graft from the ipsilateral elbow which was inserted through bone tunnels and fixed with bone anchors augmented the reconstruction. The operation was performed on 18 consecutive patients with instability after an acute traumatic dislocation. The mean follow-up was 44 months (14 to 88). There were no recurrent dislocations. The elbow was stable in 14 patients; three had some minor limitation of movement. Thirteen had no or only occasional slight pain, 15 returned to their normal level of activity and 17 were satisfied with the outcome. There was only one failure.

Nucleotide sequence and infectious cDNA clone of the L1 isolate of Pea seed-borne mosaic potyvirus.

The complete nucleotide sequence of Pea seed-borne mosaic potyvirus isolate L1 has been determined from cloned virus cDNA. The PSbMV L1 genome is 9895 nucleotides in length excluding the poly(A) tail. Computer analysis of the sequence revealed a single long open reading frame (ORF) of 9594 nucleotides. The ORF potentially encodes a polyprotein of 3198 amino acids with a deduced Mr of 363537. Nine putative proteolytic cleavage sites were identified by analogy to consensus sequences and genome arrangement in other potyviruses. Two full-length cDNA clones, p35S-L1-4 and p35S-L1-5, were assembled under control of an enhanced 35S promoter and nopaline synthase terminator. Clone p35S-L1-4 was constructed with four introns and p35S-L1-5 with five introns inserted in the cDNA. Clone p35S-L1-4 was unstable in Escherichia coli often resulting in amplification of plasmids with deletions. Clone p35S-L1-5 was stable and apparently less toxic to Escherichia coli resulting in larger bacterial colonies and higher plasmid yield. Both clones were infectious upon mechanical inoculation of plasmid DNA on susceptible pea cultivars Fjord, Scout, and Brutus. Eight pea genotypes resistant to L1 virus were also resistant to the cDNA derived L1 virus. Both native PSbMV L1 and the cDNA derived virus infected Chenopodium quinoa systemically giving rise to characteristic necrotic lesions on uninoculated leaves.

A 6-year nationwide cohort study of glycaemic control in young people with type 1 diabetes. Risk markers for the development of retinopathy, nephropathy and neuropathy. Danish Study Group of Diabetes in Childhood.

The study aimed to identify risk markers (present at the start of the study in 1989) for the occurrence and progression of microvascular complications 6 years later (in 1995) in a Danish nationwide cohort of children and adolescents with Type 1 diabetes (average age at entry 13.7 years). Probabilities for the development of elevated albumin excretion rate (AER), retinopathy, and increased vibration perception threshold (VPT) could then be estimated from a stepwise logistic regression model. A total of 339 patients (47% of the original cohort) were studied. Sex, age, diabetes duration, insulin regimen and dose, height, weight, HbA(1c), blood pressure, and AER were recorded. In addition, information on retinopathy, neuropathy (VPT), and anti-hypertensive treatment was obtained at the end of the study. HbA(1c) (normal range 4.3-5.8, mean 5.3%) and AER (upper normal limit <20 microg min(-1)) in two, timed overnight urine collections were analysed centrally. Eye examination was performed by two-field fundus photography. Determination of VPT was assessed by biothesiometry. Increased AER (> or =20 microg min(-1)) was found in 12.8% of the patients in 1995, and risk markers for this were increased AER and high HbA(1c), in 1989 (both p<0.001). Retinopathy was present in 57.8% of patients in 1995, for which the risk markers were long duration of diabetes (p<0.0001), age (p<0.01), and high HbA(1c) (p<0.0001) in 1989. Elevated VPT (>6.5 V) was found in 62.5% of patients in 1995, for which the risk markers were male sex (p<0.05), age (p<0.0001), and increased AER (p<0.05) in 1989. This study confirms that hyperglycaemia plays a major role for the development of microvascular complications in kidneys and eyes, and emphasises the need for optimal glycaemic control in children and adolescents with Type 1 diabetes.

Rapid appearance and onset of action of insulin aspart in paediatric subjects with type 1 diabetes.

UNLABELLED: The pharmacokinetics of the novel, rapid-acting insulin aspart were compared with those of soluble human insulin following subcutaneous administration in nine children (aged 6-12 years) and nine adolescents (aged 13-17 years) with stable type 1 diabetes. The study had a randomised, double-blind, two-period crossover design. Each patient received a single subcutaneous dose of insulin aspart or human insulin (0.15 IU/kg body weight) 5 min before breakfast and the plasma insulin and glucose concentrations were measured at intervals during the following 5 h. The pharmacokinetic profile of insulin aspart differed significantly from that of human insulin with a higher mean maximum serum insulin (Cmax ins), 881 +/- 321 (SD) pmol/l versus 422 +/- 193 pmol/l for human insulin (P < 0.001); and with a shorter median serum insulin tmax ins, 40.0 min (interquartile range: 40-50 min) versus 75.0 min (interquartile range: 60-120 min) for human insulin, (P < 0.001). An age-related effect on Cmax ins and area under the curve (AUC0-5 h ins) was observed with higher values in adolescents than in children for both insulin aspart and human insulin. Postprandial glycaemic control was improved with insulin aspart; the baseline-adjusted delta Cmax glu being lower for insulin aspart compared with human insulin (increase of 7.6 +/- 5.1 versus 9.4 +/- 4.4 mmol/l respectively, P < 0.05). The incidence of adverse events was similar for the two insulin types. CONCLUSION: The more rapid onset of action of insulin aspart versus human insulin, previously observed in adults, is confirmed in a paediatric population with type 1 diabetes.

[Intramedullary tuberculous abscess in a patient with liver transplantation]. / Intramedullaer tuberkuløs absces hos levertransplanteret patient.

Recipients of solid-organ transplants are, due to immunosuppressive treatment, disposed to opportunistic infections including tuberculosis. We report a rare case of acute intramedullary tuberculous abscess in a Danish male recipient of a liver transplant. The problems in diagnostics, medical and surgical treatment are discussed.

Functional and magnetic resonance imaging evaluation after single-tendon rotator cuff reconstruction.

The aim of this study was to investigate tendon integrity after surgical repair of single-tendon rotator cuff lesions. In 31 patients, 31 single-tendon repairs were evaluated. Thirty-one patients were available for clinical assessment and magnetic resonance imaging (MRI) at follow-up. A standard series of MR images was obtained for each. The results of functional assessment were scored according to the system of Constant. According to MRI evaluation, 21 (68%) patients had an intact or thinned rotator cuff and 10 (32%) had recurrence of a full-thickness cuff defect at follow-up. Patients with an intact or thinned rotator cuff had a median Constant score of 75.5 points; patients with a full-thickness cuff defect had a median score of 62 points. There was no correlation between tendon integrity on postoperative MR images and functional outcome. Patients with intact or thinned cuffs did not have significantly better functional results than patients with retorn cuffs. Because of the presence of metal artifacts and the difficulty in distinguishing postoperative scar tissue from partial tears or thinning, MRI is of minor diagnostic value in assessing the shoulder after cuff repair. However, full-thickness tears are readily diagnosed after operation with MRI.

Elbow joint kinematics after excision of the radial head.

The contribution of the radial head to elbow joint kinematics was studied in 7 osteoligamentous elbow preparations. During unloaded flexion and extension, radial head excision induced a maximum varus displacement of 1.6 degrees with 20 degrees of joint flexion and a maximum external rotation of 3.2 degrees at 110 degrees of flexion. With application of a 0.75-Nm load, radial head excision induced a maximum laxity of 3.3 degrees at 20 degrees of flexion in forced varus and a maximum laxity of 8.9 degrees at 10 degrees of flexion in forced external rotation. No laxity was observed in forced valgus or internal rotation. The results were independent of the rotation of the forearm. This study indicates that the radial head acts as stabilizer to the elbow joint in forced varus and in forced external rotation. The results suggest that fractures of the radial head cannot be treated by simple excision without altering the basic kinematics of the elbow joint.

Metabolic control and prevalence of microvascular complications in young Danish patients with Type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood.

AIMS: After Danish nationwide investigations (1987, 1989) demonstrated unacceptable blood glucose control in unselected young diabetic patients, we set out to estimate the present glycaemic control and the prevalence of microvascular complications in a cohort of children and adolescents participating in the two previous studies. METHODS: This follow-up represents 339 patients (47% of the inception cohort), median age 21.1 years (range 12.0-26.9), median diabetes duration 13.2 years (range 8.9-24.5). A standardized questionnaire, fundus photographs (with central reading) and a physical examination were performed. HbA1c and overnight albumin excretion rate (AER) were analysed centrally. RESULTS: Although 88% (n= 309) of the young persons were treated with three or more daily insulin injections, HbA1c (nondiabetic range 4.3-5.8, mean 5.3%) was 9.7+/-1.7% (mean+/-SD). Males had higher HbA1c values than females (P < 0.015). Mean daily insulin dose was 0.92+/-0.25 IU.kg(-1).24h(-1). Microalbuminuria (AER > 20-150 microg/min) and macroalbuminuria (AER > 150 microg/min) were found in 9.0% and 3.7% of the patients, respectively, and was associated with increased diastolic blood pressure (P<0.01) and presence of retinopathy (P<0.01). Retinopathy was present in approximately 60% of the patients and was associated with age, diabetes duration, HbA1c, diastolic blood pressure and AER (all P<0.01). Subclinical neuropathy (vibration perception threshold by biothesiometry > 6.5 V) was found in 62% and showed a significant association with age, linear height, diastolic blood pressure (all P < 0.01) and diabetic retinopathy (P = 0.01). CONCLUSIONS: In spite of the majority of the patients being on multiple insulin injections, only 11% had HbA1c values below 8% and the prevalence of diabetic microvascular complications in kidneys, eyes and nerves was unacceptable high.

No stabilizing effect of the elbow joint capsule. A kinematic study.

We dissected 7 cadaveric elbow specimens, leaving the collateral ligaments and the joint capsule intact. The anterior and the posterior capsule were sequentially transected, followed by kinematic testings. We found no change in joint laxity after total transection of the capsule.

Kinematics of partial and total ruptures of the medial collateral ligament of the elbow.

In this study the kinematics of partial and total ruptures of the medial collateral ligament of the elbow are investigated. After selective transection of the medial collateral ligament of 8 osteoligamentous intact elbow preparations was performed, 3-dimensional measurements of angular displacement, increase in medial joint opening, and translation of the radial head were examined during application of relevant stress. Increase in joint opening was significant only after complete transection of the anterior part of the medial collateral ligament was performed. The joint opening was detected during valgus and internal rotatory stress only. After partial transection of the anterior bundle of the medial collateral ligament was performed, there was an elbow laxity to valgus and internal rotatory force, which became significant after transection of 100% of the anterior bundle of the medial collateral ligament and was maximum between 70 degrees to 90 degrees of flexion. No radial head movement was seen after partial or total transection of the anterior bundle of the medial collateral ligament was performed. In conclusion, this study indicates that valgus or internal rotatory elbow instability should be evaluated at 70 degrees to 90 degrees of flexion. Detection of partial ruptures in the anterior bundle of the medial collateral ligament based on medial joint opening and increased valgus movement is impossible.