Decreasing incidence of ruptured abdominal aortic aneurysm already before start of screening.

BACKGROUND: The aim of this study was to evaluate whether screening for abdominal aortic aneurysm (AAA) has led to a decrease in ruptured AAA (rAAA) incidence. METHOD: The Malmö population was evaluated regarding the incidence of rAAA and elective AAA surgery 4 years before and after start of AAA-screening in 2010. Data from 1971 to 1986 (J Vasc Surg 18:74-80, 1993) and 2000-2004 (J Vasc Surg 44:237-43, 2006), enabled analysis of trends over time. RESULTS: Analysis of time-periods 1971-1986, 2000-2004, 2006-2010 and 2010-2014 showed an incidence of rAAA of 5.6 (4.9-6.3), 10.6 (8.9-12.4), 6.1 (4.6-7.6) and 4.0 (2.9-5.1), respectively. In men aged 60-69 years the incidences were 16.0 (10.7-21.3), 45.6 (27.7-63.4), 19.3 (9.2-35.3) and 8.9 (2.8-20.6), respectively. The incidences of elective AAA surgery in men aged 60-69 years were 22.9 (16.5-29.2), 34.6 (19.1-50.2), 9.7 (1.2-18.5) and 44.2 (27.0-61.6), respectively. CONCLUSIONS: A decrease in incidence of rAAA in men was evident before the implementation of screening. We were yet not able to demonstrate a certain reduction in rAAA incidence after the start of screening.

Outcome of visceral chimney grafts after urgent endovascular repair of complex aortic lesions.

OBJECTIVE: Endovascular abdominal aortic repair requires an adequate sealing zone. The chimney graft (CG) technique may be the only option for urgent high-risk patients who are unfit for open repair and have no adequate sealing zone. This single-center experience provides long-term results of CGs with endovascular repair for urgent and complex aortic lesions. METHODS: Between July 2006 and October 2012, 51 patients (16 women) with a median age of 77 years (interquartile range, 72-81 years), were treated urgently (within 24 hours [61%]) or semiurgently (within 3 days [39%]) with endovascular aortic repair and visceral CGs (n = 73). Median follow-up was 2.3 years (interquartile range, 0.8-5.0 years) for the whole cohort, 3 years for 30-day survivors, and 4.8 years for patients who are still alive. RESULTS: Five patients (10%) died within 30 days. All of them had a sacrificed kidney. All-cause mortality was 57% (n = 29), but the chimney- and procedure-related mortality was 6% (n = 3) and 16% (n = 8), respectively. Chimney-related death was due to bleeding, infection, renal failure, and multiple organ failure. There were two postoperative ruptures; both were fatal although not related to the treated disease. The primary and secondary long-term CG patencies were 89% (65 of 73) and 93% (68 of 73), respectively. Primary type I endoleak (EL-I) occurred in 10% (5 of 51) of the patients, and only one patient had recurrent EL-I (2%; 1 of 51). No secondary endoleak was observed. Chimney-related reintervention was required in 16% (8 of 51) of the patients because of EL-I (n = 3), visceral ischemia (n = 4), and bleeding (n = 2). The reinterventions included stenting (n = 5), embolization (n = 3), and laparotomy (n = 2). Thirty-one visceral branches were sacrificed (9 celiac trunks, 9 right, and 13 left renal arteries). Among the 30-day survivors, 8 of 17 patients (47%) with a sacrificed kidney required permanent dialysis; of these, seven underwent an urgent index operation. The aneurysm sac shrank in 63% (29 of 46) of cases. CONCLUSIONS: The 6% chimney-related mortality and 93% long-term patency seem promising in urgent, complex aortic lesions of a high-risk population and may justify a continued yet restrictive applicability of this technique. Most endoleaks could be sealed endovascularly. However, sacrifice of a kidney in this elderly cohort was associated with permanent dialysis in 47% of patients.

Glucose-Dependent Insulinotropic Polypeptide Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the proatherogenic cytokine osteopontin (OPN) in mouse arteries via local release of endothelin-1 and activation of CREB. Infusion of GIP increases plasma OPN concentrations in healthy individuals. Plasma endothelin-1 and OPN concentrations are positively correlated in patients with critical limb ischemia. Fasting GIP concentrations are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared with control subjects. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients, and expression associates with parameters that are characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration, and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from humans, mice, rats, and pigs, remarkable upregulation is observed in endothelial and smooth muscle cells upon culture conditions, yielding a "vascular disease-like" phenotype. Moreover, the common variant rs10423928 in the GIPR gene is associated with increased risk of stroke in patients with type 2 diabetes.

Efficacy and durability of the chimney graft technique in urgent and complex thoracic endovascular aortic repair.

OBJECTIVE: This study reports the early and midterm to long-term experience of chimney grafts (CGs) in urgent endovascular repair of complex lesions in the thoracic aorta. METHODS: Twenty-nine high-risk patients (20 men) who were unfit for open repair were treated using CG technique for ruptured (n = 14) or symptomatic (n = 15) aortic lesions engaging the aortic arch itself (n = 9), the descending aorta (n = 10), or the thoracoabdominal aorta (n = 10). Twenty-two patients (76%) were treated urgently (≤24 hours) and seven were semiurgent (≤3 days). Of 41 chimneys used, 24 were placed in supra-aortic branches and 17 in visceral branches. Median follow-up (interquartile range) for the entire cohort was 2 years (0.6-3.8 years), 2.5 years (1-4 years) for 30-day survivors, and 3.5 years (1.9-6.4 years) for those who were still alive. RESULTS: Four patients (14%) died ≤30 days of cerebral infarction (n = 1), visceral ischemia secondary to the initial rupture (n = 1), multiple organ failure (n = 1), or heart failure (n = 1). There were 11 late deaths (38%); however, only two deaths were related to the CG technique. The primary and secondary technical success rates were 86% (25 of 29) and 97% (28 of 29), respectively. The secondary patency rate of CGs was 98%. Seventeen (68%) of the aortic lesions shrank significantly. Three patients (10%) had primary type I endoleak and another three (10%) had secondary type I endoleak. The endoleaks were managed with Onyx (ev3 Endovascular, Inc, Plymouth, Minn) or coil embolization (n = 2), restenting (n = 1), and conversion to open repair (n = 2). One secondary endoleak is still under observation after >20 months. All primary endoleaks and one secondary endoleak originated from CGs in the brachiocephalic trunk (4 of 6 [67%]). CONCLUSIONS: The midterm to long-term results of the CG technique for urgent and complex lesions of the thoracic aorta in high-risk patients are promising, with low early mortality and long durability of the CGs. More patients with longer follow-up are still needed.

Inflammatory mediators after endovascular aortic aneurysm repair.

OBJECTIVE: To evaluate patterns of inflammatory mediators before and after elective endovascular aortic aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: Inflammatory mediators including soluble urokinase plasminogen activator (suPAR), endothelin (ET)-1, tumour necrosis factor (TNF)-α, interleukin (IL)-6, CD40 ligand (CD40L) and IgM antibodies against phosphorylcholine (IgM anti-PC), were evaluated before and after elective EVAR in 21 patients. Five patients undergoing open AAA repair (OR) were evaluated for comparison. RESULTS: SuPAR (p<0.001), ET-1 (p=0.003) and IL-6 (p=0.02) increased whereas IgM anti-PC decreased (p<0.001) after EVAR. Both suPAR (p=0.04) and IL-6 (p=0.03) increased in the five patients with unchanged/expanded aneurysm sac after EAR, whereas only suPAR increased (p=0.04) and IL-6 remained unchanged (p=0.2) among the 16 patients with shrinking aneurysm sac. No difference was noted between patients undergoing EVAR and OR regarding levels or changes of studied markers. CONCLUSIONS: These changes in plasma biomarker profile are compatible with on-going inflammatory activation in AAA patients after EVAR. The potential role of IL-6 as a plasma biomarker for treatment failure in surveillance programs after EVAR needs to be further evaluated.

Optimal management of renal artery fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory angiopathy of unknown cause affecting medium-sized (most commonly renal) arteries and causing renovascular hypertension. The most common medial multifocal type of FMD (with the "string of beads" appearance) is more than four times more prevalent in females than in males. FMD accounts for up to 10% of cases of renovascular hypertension. Compared with patients with atherosclerotic renal artery stenosis, patients with FMD are younger, have fewer risk factors for atherosclerosis, and a lower occurrence of atherosclerosis in other vessels. The etiology is multifactorial, including vessel wall ischemia and smoking, as well as hormonal and genetic factors. Intra-arterial digital subtraction angiography is still the gold standard for exclusion or confirmation of renal artery stenosis caused by FMD, at least in young patients, who more often have lesions in branches of the renal artery. For FMD patients with atherosclerosis and those who are older (>50-55 years), significant renal artery stenosis may be confirmed or excluded with ultrasonography. The FMD lesion is typically truncal or distal, whereas atherosclerotic lesions are more often proximal or ostial. Treatment options are medical, endovascular (percutaneous transluminal renal angioplasty [PTRA]), and surgical. Invasive treatment should be considered when hypertension cannot be controlled with antihypertensive drugs and in patients with impaired renal function or ischemic nephropathy. PTRA has become the treatment of choice and normally yields good results, especially in unifocal disease and young patients. Pressure gradients are normally completely abolished, and there is no indication for stent placement. Surgical revascularization is indicated after PTRA complications; thrombosis, perforation, progressive dissection, repeated PTRA failure or restenosis. Centralization of handling is recommended.

Equal access to health care may diminish the differences in outcome between native and immigrant patients with type 1 diabetes.

BACKGROUND/OBJECTIVE: Previous studies have found that ethnicity influences glycemic control. We hypothesized that differences between Nordic and non-Nordic patients are less pronounced for children with type 1 diabetes in high incidence countries in Northern Europe. RESEARCH DESIGN AND METHODS: We investigated patients aged 0-15 yr in national pediatric registers in Denmark (D), Iceland (I), Norway (N), and Sweden (S) (2006-2009). Ethnic origin was defined by maternal country of birth as being Nordic or non-Nordic (other countries). RESULTS: The cohort (n = 11,908, 53.0% boys, onset age 7.7 (3.9) yr, diabetes duration 6.1 (3.6) yr, [mean, (SD)]) comprised 921 (7.7%) non-Nordic patients. The frequencies of non-Nordic patients according to country of residence were: 5.7% (D), 2.7% (I), 5.5% (N), and 9.4% (S). Sex distribution and BMI z-score did not differ between Nordic and non-Nordic patients, but non-Nordic patients were 0.5 yr younger at onset than Nordic patients (p < 0.0006). Non-Nordic patients had a lower number of daily insulin bolus injections and higher daily insulin doses compared to their Nordic peers. Patients of non-Nordic origin had slightly higher HbA1c levels (0.6-2.9 mmol/mol, p < 0.001) and, with the exception of Norway, were less frequently treated with CSII (p = 0.002) after adjusting for confounders. CONCLUSIONS: The reported differences in glycemic regulation between Nordic and non-Nordic type 1 diabetes children and adolescents in four Nordic countries are diminutive, but persist after accounting for treatment intensity.

High plasma levels of islet amyloid polypeptide in young with new-onset of type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Islet amyloid polypeptide (IAPP) is a beta cell hormone secreted together with insulin upon glucose stimulation. IAPP participates in normal glucose regulation, but IAPP is also known for its ability to misfold and form islet amyloid. Amyloid fibrils form through smaller cell toxic intermediates and deposited amyloid disrupts normal islet architecture. Even though IAPP and amyloid formation are much discussed in type 2 diabetes, our aim was to study the significance of IAPP in type 1 diabetes. RESULTS: Plasma IAPP levels in children and adolescents with newly diagnosed type 1 diabetes (n = 224) were analysed and concentrations exceeding 100 pmol/L (127.2-888.7 pmol/L) were found in 11% (25/224). The IAPP increase did not correlate with C-peptide levels. CONCLUSIONS/INTERPRETATION: Plasma levels of IAPP and insulin deviate in a subpopulation of young with newly-diagnosed type 1 diabetes. The determined elevated levels of IAPP might increase the risk for IAPP misfolding and formation of cell toxic amyloid in beta cells. This finding add IAPP-aggregation to the list over putative pathological factors causing type 1 diabetes.

Islet cell antibodies (ICA) identify autoimmunity in children with new onset diabetes mellitus negative for other islet cell antibodies.

AIMS: The aim of this study was to explore whether islet cell antibodies (ICA) could be identified in children with newly onset diabetes mellitus but negative for autoantibodies against glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A), insulin (IAA), or any of the three variants with arginine (R), tryptophan (W), or glutamine (Q) at position 325 of the zinc transporter 8 (ZnT8A). METHODS: A population-based analysis of autoantibodies was performed from 1 May 2005 to 2 September 2010 in Swedish children newly diagnosed with diabetes. ICA was analyzed with an enzyme-linked immunosorbent assay and if positive, reanalyzed in the classical ICA immunofluorescence assay, in 341 samples among 3545 children who had been tested negative for all of GADA, IA-2A, IAA, or ZnT8A (R, W, Q). RESULTS: An isolated positivity for ICA was identified in 5.0% (17/341) of the newly diagnosed children. The levels of ICA in positive subjects ranged from 3 to 183 JDF-U (median 30). This finding increased the diagnostic sensitivity of islet autoimmunity as 3204/3545 patients (90.4%) were islet autoantibody positive without the ICA analyses and 3221 patients (90.9%) were positive with the inclusion of ICA. CONCLUSIONS: The finding of an isolated positivity for ICA despite negativity for GADA, IA-2A, IAA, and ZnT8A (R, W, Q) suggests that still another yet unidentified autoantigen(s) may contribute to the ICA immunofluorescence. Hence, ICA is important to analyze in type 1 diabetes children and adolescents that would otherwise be islet autoantibody negative.

External quality assessment of HbA1c and its effect on comparison between Swedish pediatric diabetes clinics. Experiences from the Swedish pediatric diabetes quality register (Swediabkids) and Equalis.

BACKGROUND: To explore to what extent measurement error can explain the variation of mean patient HbA(1c) between clinics. METHODS: For each year 2005-2010 data from 5380-6985 children, age <18 years, in 35-43 Swedish pediatric clinics was analyzed. Each year 13,000-19,000 HbA(1c) analyses were evaluated. Year mean HbA(1c) for each patient was calculated for HbA(1c) values when insulin dose was ≥0.5 U/kg. In Sweden HbA(1c) values were during the study period standardized to the Mono S level, HbA(1c)(Mono S)%, but are given also in the international unit HbA(1c)(IFCC), mmol/mol. Performance of locally measured HbA(1c) is monitored by Equalis through monthly external quality assessment (EQA) schemes. RESULTS: The yearly mean bias term for each clinic varied from -0.54 to 0.41 HbA(1c)(Mono S)%. The bias between clinic HbA(1c) and target value improved during the 6 years and the mean bias was for 79%-88% of clinics within the recommended level ±0.14 HbA(1c)% the last 2 years. Inter-clinic mean HbA(1c) had a wide interquartile range, 0.30-0.43 HbA(1c)(Mono S)% [3.2-4.5 HbA(1c)(IFCC)mmol/mol]. CONCLUSIONS: Regular participation in EQA schemes is necessary when comparing HbA(1c) values. The measurement error decreased during the 6-year period and explained from 28% to <10% of the inter-clinic variation in year mean clinic HbA(1c).

The importance of socioeconomic factors for compliance and outcome at screening for abdominal aortic aneurysm in 65-year-old men.

OBJECTIVE: To evaluate compliance with screening and prevalence of abdominal aortic aneurysm (AAA) in relation to background data regarding area-based socioeconomic status. METHODS: Our department annually invites 4300 65-year-old men from the city of Malmö and 15 neighboring municipalities to ultrasound AAA screening. In a cross-sectional cohort study, compliance and AAA prevalence among 8269 men were related to background socioeconomic data such as mean income, proportion of immigrants, percentage of subjects on welfare, smoking habits, and unemployment rate in the different municipalities. The 10 different administrative areas in Malmö were evaluated separately. RESULTS: Compliance with screening in the entire area was 6630/8269 (80.2%) but varied between 64.4% and 89.3% in different municipalities (P < .001). In univariate analysis, compliance increased with increasing mean income (r = 0.873; P < .001) but decreased with increasing proportion of immigrants (r = -0.685; P =.005) and subjects on welfare (r = -0.698; P = .004). Compliance in 10 different administrative parts of Malmö (P = .002) also increased with increasing mean income (r = 0.948; P < .001), and decreased with increasing proportion of immigrants (r = -0.650; P = .042) and increasing unemployment rate (r = -0.796; P = .006). Altogether, 117 (1.8%) AAAs were found, the prevalence differing between both different municipalities (P =.003) and the 10 different administrative parts of Malmö (P =.02). The prevalence of AAA in the 10 administrative parts of Malmö increased with increasing percentage of smokers (r = 0.784; P = .007), percentage of immigrants (r = 0.644; P = .044), and unemployment rate (r = 0.783; P =.007) but decreased with increasing mean income (r = -0.754; P = .012). CONCLUSIONS: Compliance with ultrasound screening for AAA differed between different geographical areas. In areas with low socioeconomic status, compliance rates were lower, whereas AAA prevalence was higher. The identification of contextual factors associated with low compliance is important to be able to allow targeted actions to increase efficacy of ultrasound screening for AAA. Targeted actions to increase compliance in those areas are being scientifically investigated and implemented.

Decline of C-peptide during the first year after diagnosis of Type 1 diabetes in children and adolescents.

AIMS/HYPOTHESIS: We studied the decline of C-peptide during the first year after diagnosis of Type 1 diabetes (T1D), and its relation to various factors. METHODS: 3824/4017 newly diagnosed patients (95%) were classified as T1D in a national study. In a non-selected subgroup of 1669 T1D patients we determined non-fasting C-peptide both at diagnosis and after 1 year, and analyzed decline in relation to clinical symptoms and signs, initial C-peptide and occurrence of auto-antibodies. RESULTS: Younger children lost more C-peptide (p<0.001) and the higher the C-peptide at diagnosis the larger the decline during the first year (p<0.0000). Patients with higher BMI had higher C-peptide at diagnosis but lost more (p<0.01), and those with lower HbA1c, without symptoms and signs at diagnosis, and with higher BMI, had higher C-peptide at diagnosis, but lost more during the first year (p<0.001). Finally, patients diagnosed during autumn had higher C-peptide at diagnosis, but lost more during the coming year (p<0.001). Occurrence of auto-antibodies did not correlate with C-peptide decline, except possibly for a more rapid loss in IAA-positive patients. CONCLUSIONS/INTERPRETATION: Even in a restricted geographical area and narrow age range (<18 years), the natural course of Type 1 diabetes is heterogeneous. This should be considered in clinical trials.

APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] µg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 µg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

APC resistance due to Factor V Leiden is not related to baseline inflammatory mediators or survival up to 10 years in patients with critical limb ischemia.

To prospectively evaluate the potential influence of resistance to activated protein C (APC-resistance) on the initial inflammatory response, amputation rate and survival during 10 years of follow-up in patients with critical limb ischemia (CLI). Two hundred and fifty-six consecutive CLI patients were analyzed for APC-ratio, the Factor V Leiden mutation and inflammatory mediators and then prospectively followed for 10 years. Inflammatory mediators, amputation rate, morbidity and mortality were compared between patients with and without APC resistance. Of the 256 CLI patients, 35 (14 %) were heterozygotes and 2 (1 %) homozygotes for the Factor V gene mutation, whereas 219 (86 %) patients were non-APC resistant. No significant differences were found between APC resistant and non-APC resistant patients regarding inflammatory mediators. Non-APC resistant patients more often had infrainguinal atherosclerosis (172 [79 %] vs 22 [59 %]; p = 0.017). Amputation rate at 1 year did not differ. Furthermore, there were no significant differences between groups regarding 1-, 3-, 5-, or 10-year survival. APC resistance in patients with CLI was not related to inflammatory activity, and had no impact on limb salvage or rate of amputation or long-term mortality. APC-resistant CLI-patients less frequently had infrainguinal arteriosclerosis, however.

Socioeconomic factors and concomitant diseases are related to the risk for venous thromboembolism during long time follow-up.

While the risk for arterial vascular disease has been shown to be influenced by socioeconomic status (SES), there is limited information whether SES also influences the risk for venous thromboembolism (VTE). To evaluate whether there is an association between SES and VTE incidence. In 1990, all 730,050 inhabitants (379,465 women and 350,585 men) above 25 years of age in the County of Skåne in Sweden were evaluated with regard to age, household income, marital status, country of birth, number of years of residence in Sweden, educational level, and concomitant diseases. The cohort was hereafter prospectively investigated regarding diagnosis of, or death from VTE (deep venous thrombosis or pulmonary embolism ), during 1991-2003. The association between socioeconomic data and concomitant diseases at the baseline investigation 1990 and incidence of VTE during follow-up was examined by Cox proportional hazard models. During the 13 years prospective follow-up, 10,212 women and 7,922 men were diagnosed with VTE. In both genders, age above 40 years at baseline, low income, single status, and a lower level of education were associated with an increased risk of VTE. However, both men and women born outside of Sweden have a lower risk for VTE during follow-up, however. Age above 40 years, low income, single marital status, and lower level of education were independently related to an increased risk of VTE diagnosis during 13 years of prospective follow-up.

Chimney grafts preserve visceral flow and allow safe stenting of juxtarenal aortic occlusion.

OBJECTIVE: Chimney grafts have proven useful for urgent endovascular repair of juxtarenal aortic aneurysms. Stenting of juxtarenal aortic occlusive disease is not routinely advocated due to the risk of visceral artery obstruction. We report on the potential applicability of chimney grafts in 10 patients with juxtarenal aortic stenosis or occlusion. To our best knowledge, chimney grafts have not been applied previously in this challenging setting. METHODS: Ten high-risk female patients (mean age, 68 years) with severe stenosis or occlusion of the aorta at the level of the visceral arteries were offered stenting. "Chimney" stents or stent grafts (20-40 mm long) were implanted from a brachial approach into visceral arteries that needed to be covered by the aortic stent. The chimney stents were then temporarily obstructed by balloon catheters to prevent visceral embolization until the aortic stent or stent graft was deployed. RESULTS: All procedures were technically successful, and patency was obtained in all visceral arteries and the aorta without distal embolization. One patient died after 9 days of acute heart failure. The nine surviving patients presented no complications, and all stented vessels remained patent at up to 6 years. Another patient died after 5.5 years due to lung cancer. All three patients with renal impairment have improved renal function, and a reduction in antihypertensive medication has been possible. CONCLUSIONS: Chimney grafts may allow stenting of juxtarenal aortic occlusive disease by protecting the patency of visceral arteries. Further evaluation with more patients and longer follow-up is required.

Hormonal response during physical exercise of different intensities in adolescents with type 1 diabetes and healthy controls.

BACKGROUND: Physical activity is a critical component in the care of diabetes. Although it offers health benefits it presents challenges. OBJECTIVE: To investigate differences between adolescent boys and girls with type 1 diabetes and healthy controls in terms of maximal work capacity (VO(2) max) and hormonal response to physical exercise of different intensities. SUBJECTS: Twelve individuals (six boys and six girls; age 14-19 yr, pubertal stage 4-5) with type 1 diabetes (duration, 6.3 ± 4.4 yr; hemoglobin A1c, 63 ± 10 mmol/mol) were compared with 12 healthy controls matched for age, sex, pubertal stage, body mass index standard deviation score, and amount of regular physical activity. METHODS: During consecutive days, three different workloads; maximal, endurance, and interval, were performed on an Ergometer cycle. During the tests, levels of lactate, glucose, insulin, and regulatory hormones [glucagon, cortisol, growth hormone (GH), adrenaline, and noradrenaline] were measured in blood. Subcutaneous glucose was measured continuously. RESULTS: VO(2) max did not differ between the groups, diabetes 49.8 ± 9.9 vs. control 50.7 ± 12.0 mL/min/kg. Hormonal responses did not differ between the groups except for mean peak GH level during the interval test, diabetes 63.2 ± 27.0 vs. control 33.8 ± 20.9 mU/L, p < 0.05. CONCLUSIONS: Physical capacity and hormonal regulation of blood glucose in connection with physical exercise of different intensities did not differ between adolescents with diabetes and healthy controls. Thus, adolescents with type 1 diabetes can participate in physical activity on the same terms as healthy peers.

Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.

OBJECTIVES: The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. BACKGROUND: It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. METHODS: The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (n(e) = 4,572); venous thromboembolism (n(e) = 4,607); intracranial aneurysm (n(e) = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). RESULTS: LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 × 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 × 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 × 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 × 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 × 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). CONCLUSIONS: LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes.

Zinc transporter 8 autoantibodies and their association with SLC30A8 and HLA-DQ genes differ between immigrant and Swedish patients with newly diagnosed type 1 diabetes in the Better Diabetes Diagnosis study.

We examined whether zinc transporter 8 autoantibodies (ZnT8A; arginine ZnT8-RA, tryptophan ZnT8-WA, and glutamine ZnT8-QA variants) differed between immigrant and Swedish patients due to different polymorphisms of SLC30A8, HLA-DQ, or both. Newly diagnosed autoimmune (≥1 islet autoantibody) type 1 diabetic patients (n = 2,964, <18 years, 55% male) were ascertained in the Better Diabetes Diagnosis study. Two subgroups were identified: Swedes (n = 2,160, 73%) and immigrants (non-Swedes; n = 212, 7%). Non-Swedes had less frequent ZnT8-WA (38%) than Swedes (50%), consistent with a lower frequency in the non-Swedes (37%) of SLC30A8 CT+TT (RW+WW) genotypes than in the Swedes (54%). ZnT8-RA (57 and 58%, respectively) did not differ despite a higher frequency of CC (RR) genotypes in non-Swedes (63%) than Swedes (46%). We tested whether this inconsistency was due to HLA-DQ as 2/X (2/2; 2/y; y is anything but 2 or 8), which was a major genotype in non-Swedes (40%) compared with Swedes (14%). In the non-Swedes only, 2/X (2/2; 2/y) was negatively associated with ZnT8-WA and ZnT8-QA but not ZnT8-RA. Molecular simulation showed nonbinding of the relevant ZnT8-R peptide to DQ2, explaining in part a possible lack of tolerance to ZnT8-R. At diagnosis in non-Swedes, the presence of ZnT8-RA rather than ZnT8-WA was likely due to effects of HLA-DQ2 and the SLC30A8 CC (RR) genotypes.