Chronic Total Occlusion Interventions in Patients with Reduced Ejection Fraction.

PURPOSE OF THE REVIEW: The goal of this paper is to review the current evidence surrounding CTO PCI in patients with low EF, the most high-risk population to treat. We also present pertinent case examples and offer practical tips to increase success and lower complications when performing CTO PCI in patients with low EF. RECENT FINDINGS: In a prospective randomized control study, greater improvement in angina frequency and quality of life, assessed by the Seattle Angina Questionnaire, was achieved by CTO PCI compared to optimal medical therapy. Furthermore, after successful CTO PCI, improvements in health status were similar in patients with both low and normal EF. CTO PCI can not only ameliorate symptoms of angina in patients with low EF but may also potentially improve EF in carefully selected populations. However, information regarding treatment of this high-risk population is lacking and large-scale studies targeting patients with severely reduced EF remain necessary.

Thirty-Year Time Trends in Diabetic Retinopathy and Macular Edema in Youth With Type 1 Diabetes.

OBJECTIVE: To examine trends in diabetic retinopathy (DR) and diabetic macular edema (DME) in adolescents with type 1 diabetes between 1990 and 2019. RESEARCH DESIGN AND METHODS: We analyzed 5,487 complication assessments for 2,404 adolescents (52.7% female, aged 12-20 years, diabetes duration >5 years), stratified by three decades (1990-1999, 2000-2009, 2010-2019). DR and DME were graded according to the modified Airlie House classification from seven-field stereoscopic fundal photography. RESULTS: Over three decades, the prevalence of DR was 40, 21, and 20% (P < 0.001) and DME 1.4, 0.5, and 0.9% (P = 0.13), respectively, for 1990-1999, 2000-2009, and 2010-2019. Continuous subcutaneous insulin infusion (CSII) use increased (0, 12, and 55%; P < 0.001); mean HbA1c was bimodal (8.7, 8.5, and 8.7%; P < 0.001), and the proportion of adolescents meeting target HbA1c <7% did not change significantly (8.3, 7.7, and 7.1%; P = 0.63). In multivariable generalized estimating equation analysis, DR was associated with 1-2 daily injections (odds ratio 1.88, 95% CI 1.42-2.48) and multiple injections in comparison with CSII (1.38, 1.09-1.74); older age (1.11, 1.07-1.15), higher HbA1c (1.19, 1.05-1.15), longer diabetes duration (1.15, 1.12-1.18), overweight/obesity (1.27, 1.08-1.49) and higher diastolic blood pressure SDS (1.11, 1.01-1.21). DME was associated with 1-2 daily injections (3.26, 1.72-6.19), longer diabetes duration (1.26, 1.12-1.41), higher diastolic blood pressure SDS (1.66, 1.22-2.27), higher HbA1c (1.28, 1.03-1.59), and elevated cholesterol (3.78, 1.84-7.76). CONCLUSIONS: One in five adolescents with type 1 diabetes had DR in the last decade. These findings support contemporary guidelines for lower glycemic targets, increasing CSII use, and targeting modifiable risk factors including blood pressure, cholesterol, and overweight/obesity.

A microanalysis of expert-student dialogue videos: Supporting preparation and learning for clinical competence assessment.

INTRODUCTION: The aim of this qualitative study was to analyse students' perceptions and impact of using a novel video genre designed to support their learning and preparation for a clinical competence assessment. The videos demonstrate expert-student dialogue (ESD) of authentic, one-on-one discourse between the teacher and student, relating to the case presentation and self-evaluation of the assessment. METHODS: Students who were about to perform a competence assessment were invited to participate in the study. Students were asked to watch a relevant ESD video they had not previously had access to, which showed the examiner-examinee dialogue relating to a peer's tooth preparation for the competence assessment. Immediately after watching the video, a video simulated recall approach was performed to analyse students' perceptions. Thematic analysis was performed to induce relevant themes. RESULTS: Five themes were identified: analysis and judgement, observational learning from expert dialogue, observational learning from student dialogue, self-efficacy and empathy. Positive responses from interviews suggested high cognitive engagement with this video genre with an affective component that was also valued as an informative learning resource. Students reported the video could stimulate them to think, make it easier to remember knowledge, avoid errors observed, and gain insights into assessment process and examiner's expectations. Empathy was also reported towards the examinee in the video. CONCLUSIONS: The ESD videos facilitated students' active and analytical thinking as well as improved their assessment preparedness. This video genre has shown how observing ESD can support students' learning and preparation for a clinical competence assessment.

Cultural Considerations in Debriefing.

SUMMARY STATEMENT: Culture influences how we communicate, teach, and learn. Debriefings are laden with cultural influences. Without attention to cultural considerations, accepted debriefing techniques might not reach the desired outcome and, in certain cultures, may even harm teacher-learner relationships. We explore cultural considerations in healthcare simulation debriefing and offer guidance for debriefers to gain awareness of potential cultural biases.

An exploration of student access to a learning management system-challenges and recommendations for educators and researchers.

INTRODUCTION: This study examined student access to online resources of a faculty's learning management system (LMS). Issues relating to current e-learning resources usage were identified and formed the basis for recommendations to help assist stakeholders in teaching, learning and research. METHODS: Learning analytics from four cohorts of undergraduate dental students were extracted from the database of a LMS spanning between 2012 and 2016. Individual datasets were combined into one master file, re-categorised, filtered and analysed based on cohort, year of study, course and nature of online resource. RESULTS: A total of 157,293 access events were documented. The proportion of administrative to learning data varied across cohorts, with oldest cohort having the highest ratio (82:18) in their final year and most recent cohort having a ratio of 33:67 in their 4th year demonstrating a higher proportion to learning. Seven Learning domains were identified in the access data: access to problem-based learning resources was the highest and next was fixed prosthodontics videos. The prosthodontics discipline had the highest access across the curriculum while some others had very limited or even no learning access events. CONCLUSION: A number of limitations have been identified with the analytics and learning resources in this LMS and engagement with learning resource provision. More detailed data capture of access use and unique identifiers to resources as well as keyword tagging of the resources are required to allow accurate mapping and support of students learning. Moreover, motivation or nudging of students behaviour to more actively engage with learning content needs exploration.

The relation of online learning analytics, approaches to learning and academic achievement in a clinical skills course.

INTRODUCTION: This study examined relationships of students' access of e-learning (learning analytics) for a healthcare psychomotor skills course, approaches to learning (R-SPQ-2F psychometric) and academic achievement (summative examination results). An understanding of the relationships may help in supporting students learning. METHODS: Two consecutive cohorts of 5th year dental students were asked to complete the R-SPQ-2F questionnaire and permission to access data of online videos and associated quizzes and two summative written examination results were examined. The summative assessments were an OSCA and a written-paper question both in prosthodontics. Multiple linear regression and correlation analysis were performed. RESULTS: Students (n=98) performed a total of 10470 video access events and 7714 attempts in online quizzes. Deep learning approach was the strongest predictor variable (ß=0.270; P=.004) on written-paper question result. While video and quiz access were moderately correlated (r=0.600; P<.001) to each other, video access was not a significant predictor to either of the examination results. Quiz access was negatively associated with academic achievement for the written-paper question results (ß=-0.349; P<.001). CONCLUSIONS: Only deep approach to learning appeared to be relevant for the written-paper question examination grades. Conversely, the number of video and quiz access did not relate to either examination results. This suggests e-learning access and examinations do not appear to relate under the conditions explored. Other attributes of learning management access may need to be explored to determine if access to learning management systems may be useful in offering remedial support to students.

Obesity and Ventricular Repolarization: a Comprehensive Review.

Obesity is known to be a strong predictor of sudden cardiac death. For this reason, concern exists that this association may be related to delayed ventricular repolarization (VR), which has been extensively studied in overweight and obese patients. The corrected QT interval (QTc) and QT or QTc dispersion have been the most commonly-used electrocardiographic methods for assessing VR. Multiple controlled studies demonstrated that QTc and QT or QTc dispersion were significantly longer/greater in overweight and obese subjects than in normal weight controls. The preponderance of evidence indicates that weight loss in overweight and obese patients, whether achieved by diet or bariatric surgery, significantly shortens QTc and decreases QT or QTc dispersion. Several co-morbidities that are commonly associated with obesity may delay VR. These include diabetes mellitus, the metabolic syndrome, systemic hypertension, left ventricular hypertrophy, heart failure, and obstructive sleep apnea. It is unclear whether overweight and obesity are independent predictors of delayed VR. It is also uncertain whether prolongation of QTc in such patients is sufficient to predispose to potentially fatal ventricular arrhythmias.

Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral Nerve Abnormality.

OBJECTIVE: To compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI). RESEARCH DESIGN AND METHODS: Prospective cohort of 989 patients (aged 12-20 years; diabetes duration >5 years) treated with CSII or MDI for >12 months. Microvascular complications were assessed from 2000-14: early retinopathy (seven-field fundal photography), peripheral nerve function (thermal and vibration threshold testing), autonomic nerve abnormality (heart rate variability analysis of electrocardiogram recordings) and albuminuria (albumin creatinine ratio/timed overnight albumin excretion). Generalized estimating equations (GEE) were used to examine the relationship between treatment and complications rates, adjusting for socio-economic status (SES) and known risk factors including HbA1c and diabetes duration. RESULTS: Comparing CSII with MDI: HbA1C was 8.6% [70mmol/mol] vs. 8.7% [72 mmol/mol]) (p = 0.7), retinopathy 17% vs. 22% (p = 0.06); microalbuminuria 1% vs. 4% (p = 0.07), peripheral nerve abnormality 27% vs. 33% (p = 0.108) and autonomic nerve abnormality 24% vs. 28% (p = 0.401). In multivariable GEE, CSII use was associated with lower rates of retinopathy (OR 0.66, 95% CI 0.45-0.95, p = 0.029) and peripheral nerve abnormality (OR 0.63, 95% CI 0.42-0.95, p = 0.026), but not albuminuria (OR 0.46, 95% CI 0.10-2.17, p = 0.33). SES was not associated with any of the complication outcomes. CONCLUSIONS: In adolescents, CSII use is associated with lower rates of retinopathy and peripheral nerve abnormality, suggesting an apparent benefit of CSII over MDI independent of glycemic control or SES.

Analysis of insulin pump settings in children and adolescents with type 1 diabetes mellitus.

AIM: To characterize current insulin pump settings used in young patients with type 1 diabetes mellitus (T1DM) and to assess their relationship to glycemic control. METHODS: This retrospective study included patients aged <18 yr old with T1DM >1 yr using a Medtronic pump device. Pump data including number of blood glucose (BG) tests per day, basal and bolus insulin parameters, carbohydrate ratio (CR), and insulin sensitivity factors (ISFs) were averaged over 14 d for statistical analyses. Anthropometric data and recent glycosylated hemoglobin A1c (HbA1c) were recorded. RESULTS: A total of 292 patients (144 males and 148 females) were included in the study. Participants had a median age (interquartile range, IQR) of 12.9 yr (10.0-15.1 yr) and pump duration of 2.8 yr (1.5-4.2 yr). No significant differences in median HbA1c (IQR) were observed in preschool [n = 14; HbA1c 7.8% (7.3-8.3%)], prepubertal [n = 105; HbA1c 8.1% (7.7-8.9%)], and adolescent subjects [n = 173; HbA1c 8.4% (7.7-9.0%)]. Adolescents took significantly fewer boluses and BG tests per day compared with younger children (p < 0.05). Age-specific diurnal variation in basal insulin delivery was noted. Additionally, stronger carbohydrate cover and weaker corrections were used in real-life compared with theoretical 500 and 100 rules, respectively. Lower HbA1c was associated with higher number of daily boluses, greater number of BG tests per day, lower average CR/500 rule ratio, and higher average ISF/100 rule ratio adjusted for age (R(2) = 0.22; p < 0.01). CONCLUSION: Insulin pump therapy requires continuous adjustments and glycemic targets are achieved by a minority. We believe this is the first study in pediatric cohort looking at association between CR and ISF with glycemic control.

Prognostic variables for clinical outcomes in valvular heart disease patients with moderate to severe secondary tricuspid regurgitation.

BACKGROUND AND AIM OF THE STUDY: Secondary tricuspid regurgitation (STR) is frequently seen in cardiology practice. Currently, few data are available on the prognostic variables associated with moderate or severe STR on death and progression to valve surgery. Hence, the study aim was to identify these prognostic variables. METHODS: In this retrospective study, patients with at least moderate STR were identified from an ongoing database and followed until death, any valvular heart surgery, or the end of the study. Clinical and echocardiographic variables including age, gender, coronary artery disease, device implantation (defibrillator or pacemaker), pulmonary disease, left ventricular ejection fraction, right ventricular size, right ventricular systolic pressure (RVSP), STR severity and concomitant valve disease were recorded. End-points were death and valve surgery. RESULTS: The average age of the 92 study participants was 68 +/- 16 years. During a mean follow up of 43 +/- 24 months, there were 13 deaths (14%) and 12 surgeries (13%). In multivariate analysis, both an elevated RVSP and device implantation were significant predictors of death (p = 0.0038 and 0.0487, respectively). Only an elevated RVSP was predictive of surgery (p = 0.05) and surgery-free survival (p = 0.0005). A RVSP > 48 mmHg had a hazard ratio of 3.93 (p = 0.0012) and a high diagnostic accuracy for predicting death, with an area under the receiver operating characteristic curve of 0.73. CONCLUSION: In patients with valvular heart disease and at least moderate STR, an elevated RVSP of at least 48 mmHg was associated with significantly increased mortality and decreased surgery-free survival.

A flexible diet using an insulin to carbohydrate ratio for adolescents with type 1 diabetes - a pilot study.

BACKGROUND & AIMS: There is significant interest in the utility of flexible meal plans for individuals with type 1 diabetes. However, there is a paucity of data examining this approach in adolescents. The aim of this study was to assess glycemic control, weight status and quality of life over 12 months in adolescents with type 1 diabetes, who were commenced on a flexible meal plan using an insulin to carbohydrate ratio. METHODS: 38 adolescents with type 1 diabetes were recruited and 28 completed the study. Glyceamic control, weight status and quality of life were measured using haemoglobin A1c, BMI and the Diabetes Quality of Life -Youth questionnaire. RESULTS: Nine months after the adolescents were transitioned to a flexible meal and insulin plan, mean BMI SDS decreased (by 0.15 ± 0.20; P < 0.001) and haemoglobin A1c increased (by 0.7 ± 0.83%; P = 0.001). Adolescents reported no change in the impact or concerns about diabetes. However, mean life satisfaction scores increased (5.5 ± 9.5; P = 0.008). CONCLUSIONS: On a flexible meal and insulin plan glycemic control deteriorated although weight status and life satisfaction, two outcomes which may be important to the adolescents, improved. A flexible meal and insulin plan warrants further investigation as a management option.

Continued reduction in the prevalence of retinopathy in adolescents with type 1 diabetes: role of insulin therapy and glycemic control.

OBJECTIVE: To examine trends in microvascular complications in adolescents with type 1 diabetes between 1990 and 2009 in Sydney, Australia. RESEARCH DESIGN AND METHODS: We used analysis of complications in 1,604 adolescents (54% female, aged 12-20 years, median duration 8.6 years), stratified by four time periods using Generalized Estimation Equations as follows: T1 (1990-1994), T2 (1995-1999), T3 (2000-2004), and T4 (2005-2009). Early retinopathy was detected using seven-field fundal photography, albumin excretion rate (AER) using timed overnight urine collections, and albumin-to-creatinine ratio (ACR) and peripheral nerve function using thermal and vibration threshold. RESULTS: Retinopathy declined (53, 38, 23, and 12%; P < 0.001), as did borderline elevation of AER/ACR (45, 30, 26, and 30%; P < 0.001) and microalbuminuria (8, 4, 3, and 3%; P = 0.006). Multiple daily injections (MDI)/continuous subcutaneous insulin infusion (CSII) use increased (17, 54, 75, and 88%; P < 0.001), median HbA(1c) decreased (9.1, 8.9, 8.5, and 8.5%; P < 0.001), and severe hypoglycemia was unchanged (6, 8, 10, and 7%; P = 0.272). Retinopathy was associated with diabetes duration (odds ratio [OR] 1.12 [95% CI 1.08-1.17]), age (1.13 [1.06-1.20]), HbA(1c) (1.16 [1.08-1.25]), systolic blood pressure (BP) SDS (1.31 [1.16-1.48]), socioeconomic disadvantage (1.42 [1.04-1.95]), and 1 to 2 injections per day (vs. MDI/CSII; 1.35 [1.05-1.73]); borderline AER/ACR with male sex (1.32 [1.02-1.70]), age (1.19 [1.12-1.26]), HbA(1c) (1.18 [1.08-1.29]), weight SDS (1.31 [1.21-1.53]), insulin dose per kilograms (1.64 [1.13-2.39]), 1 to 2 injections per day (1.41 [1.08-1.84]), and socioeconomic disadvantage (1.68 [1.23-2.31]); and microalbuminuria with age (1.14 [1.01-1.29]), HbA(1c) (1.20 [1.05-1.37]), diastolic BP SDS (1.76 [1.26-2.46]), and 1 to 2 injections per day (1.95 [1.11-3.41]). CONCLUSIONS: The decline in retinopathy supports contemporary guidelines that recommend lower glycemic targets and use of MDI/CSII in children and adolescents with type 1 diabetes.

Arm exercise stress perfusion imaging predicts clinical outcome.

Treadmill exercise capacity in resting metabolic equivalents (METs) and stress hemodynamic, electrocardiographic (ECG), and myocardial perfusion imaging (MPI) responses are independently predictive of adverse clinical events. However, limited data exist for arm ergometer stress testing (AXT) in patients who cannot perform leg exercise because of lower extremity disabilities. We sought to determine the extent to which AXT METs, hemodynamic, ECG, and MPI responses to arm exercise add independent incremental value to demographic and clinical variables for prediction of all-cause mortality, myocardial infarction (MI), or late coronary revascularization, individually or as a composite. A prospective cohort of 186 patients aged 64 ± 10 (SD) yr, unable to perform lower extremity exercise, underwent AXT MPI for clinical reasons between 1997 and 2002, and were followed for 62 ± 23 mo, to an endpoint of death or 12/31/2006. Average annual rates were 5.4% for mortality, 2.2% for MI, 2.5% for late coronary revascularization, and 8.0% for combined events. After adjustment for age and clinical variables, AXT METs [P < 0.05; hazard ratio (HR) = 0.59; confidence interval (CI) = 0.35-0.84] and abnormal MPI (P < 0.01; HR = 2.48; CI = 2.15-2.81) were independently predictive of mortality. A positive AXT ECG (P < 0.05; HR = 2.61; CI = 2.13-3.10) was predictive of MI. Death and MI combined were prognosticated by METs (P < 0.05; HR = 0.63; CI = 0.41-0.85), MPI (P < 0.05; HR = 1.77; CI = 1.49-2.05), and a positive AXT ECG (P < 0.05; HR = 1.86; CI = 1.55-2.17). In conclusion, for high risk older patients who cannot perform leg exercise because of lower extremity disabilities, AXT METs are as important as MPI for prediction of mortality alone and death and MI combined, and a positive AXT ECG prognosticates MI alone and death and MI combined.

Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1 diabetes.

OBJECTIVE: To examine the hypothesis that vitamin D deficiency (VDD) is associated with an increased prevalence of microvascular complications in young people with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a cross-sectional study of 517 patients, 25-hydroxyvitamin D was measured. Retinopathy was assessed by 7-field stereoscopic retinal photography, peripheral neuropathy by thermal and vibration threshold testing, and microalbuminuria by albumin excretion rate or albumin-to-creatinine ratio. RESULTS: Retinopathy prevalence was higher in cases with VDD versus sufficiency (18 vs. 9%, P = 0.02); deficiency was not associated with microalbuminuria or neuropathy. In logistic regression, retinopathy was associated with VDD (odds ratio 2.12 [95% CI 1.03-4.33]), diabetes duration (1.13, 1.05-1.23), and HbA(1c) (1.24, 1.02-1.50). CONCLUSIONS: VDD is associated with an increased prevalence of retinopathy in young people with type 1 diabetes. The inflammatory and angiogenic effects of VDD may contribute to early retinal vascular damage; however, further investigations are warranted.

Dobutamine stress echocardiography Doppler estimation of cardiac diastolic function: a simultaneous catheterization correlation study.

BACKGROUND: Doppler echocardiography using the ratio of early diastolic transmitral velocity to early diastolic mitral annular tissue velocity (E/E') is routinely used to evaluate left ventricular (LV) filling pressures at rest. We tested the hypothesis that measurement of E/E' in patients undergoing dobutamine stress echocardiography (DSE) will detect changes in LV filling pressures. METHODS: In this prospective study, 16 patients with normal LV ejection fraction and normal coronary arteries by angiography underwent a standard DSE protocol with simultaneous LV filling pressure monitoring with a fluid filled pigtail catheter. Doppler echocardiographic assessment of LV diastolic function was performed using E/E' at rest and during DSE. RESULTS: The average age of the study participants was 57 ± 8 years. Average heart rate was 61 ± 11 bpm at baseline and 141 ± 12 bpm at peak stress. LV mean diastolic pressure decreased from 12.3 ± 2.6 mmHg at baseline to 9.0 ± 2.3 mmHg at peak stress (P = 0.0001). Baseline E/E' at the septum and lateral annulus were 8.7 ± 2.2 and 7.5 ± 1.9 and during peak stress were 8.3 ± 3.1 and 7.9 ± 3.5, respectively. There was no significant change in E/E' at either the septum or the lateral annulus (P = 0.55, P = 0.66). There was no significant correlation between LV mean diastolic pressure and E/E' with dobutamine stress. CONCLUSIONS: In patients with normal LV ejection fraction and no significant coronary artery disease undergoing DSE, the ratio of early diastolic transmitral velocity to early diastolic tissue velocity (E/E') at peak stress with dobutamine does not predict changes in LV filling pressures.

Myocardial perfusion imaging analysis in patients with regurgitant valvular heart disease.

BACKGROUND/AIM: We noticed that there was decreased correlation of the findings from myocardial perfusion imaging (MPI) and cardiac catheterization (CATH) in patients with mitral regurgitation (MR) and aortic regurgitation (AR) compared to patients without valve disease. METHODS: Through a systematic review of MPI records at the Harry S. Truman Memorial Veterans' Hospital between 1998 and 2008, we identified 58 patients with at least moderate MR or AR by echocardiogram who underwent cardiac catheterization within 6 months of the MPI study. A control group was formulated with 60 patients who did not have significant MR or AR on echocardiogram and who had both MPI and CATH. Correlation between MPI and CATH was graded as complete, partial, or absent. RESULTS: Correlation between MPI and CATH was lower in the valve disease patients (study group) when compared to controls. Correlation was complete in 76% of study patients and 90% of controls, partial in 15% of study patients and 5% of controls, and absent in 9% of study patients and 5% of controls. Differences between the groups were significant (P < .05). CONCLUSIONS: Patients with regurgitant valvular heart disease may have myocardial perfusion abnormalities that are not associated with angiographic critical coronary stenosis.

Management of premature ventricular complexes.

Premature ventricular contractions (PVCs) are frequently encountered, and management is determined by symptoms, precipitating factors, and the presence of underlying cardiac disease. No treatment is indicated in patients with asymptomatic PVCs in absence of cardiac disease. Symptomatic patients without cardiac disease may be managed by identifying and correcting reversible causes. In patients with cardiac disease, management includes treating the underlying cardiac disease to improve both symptoms and prognosis.

Autonomic nerve testing predicts the development of complications: a 12-year follow-up study.

OBJECTIVE: Cardiac autonomic nerve tests have predicted increased mortality in adults with diabetes, predominantly due to nephropathy, cardiac disease, and hypoglycemia. The significance of subclinical autonomic nerve test abnormalities has not been systematically studied in adolescents. We aimed to reassess an adolescent cohort, whose autonomic nervous system had been tested 12 years earlier by both pupillometry and cardiovascular tests. RESEARCH DESIGN AND METHODS: From 1990 to 1993, adolescents with type 1 diabetes (n = 335) were assessed for autonomic neuropathy (median age 14.7 years [interquartile range 13.0-16.8], duration of diabetes 6.3 years [4.0-9.6], and A1C 8.3% [7.5-9.4]). Between 2003 and 2005, contact was made with 59% of the original group. Individual assessment 12 years later included completion of a validated hypoglycemia unawareness questionnaire (n = 123) and urinary albumin-to-creatinine ratio (n = 99) and retinal (n = 102) screening, as well as analysis of reports from external doctors (n = 35). RESULTS: At baseline, there was no difference in age, duration of diabetes, or complications between those who participated in the follow-up phase (n = 137) and those who did not participate (n = 196). However, baseline A1C was lower in the follow-up participants (8.2 vs. 8.5% for participants vs. nonparticipants, respectively, P = 0.031). At 12 years of follow-up, 93% were aware and 7% were unaware that they had hypoglycemia; 32 (31%) had no retinopathy, but 10% required laser therapy, and 80 (81%) had no microalbuminuria. Small pupil size at baseline was independently associated with the development of microalbuminuria (odds ratio 4.36 [95% CI 1.32-14.42], P = 0.016) and retinopathy (4.83 [1.3-17.98], P = 0.019) but not with the development of hypoglycemia unawareness. There was no association with baseline cardiovascular tests and the development of complications 12 years later. CONCLUSIONS: In this study, we found an association between baseline pupillometry tests and the presence of microalbuminuria and retinopathy at 12 years of follow-up. This suggests that pupillometry abnormalities may be early indicators of patients who are at high risk of future microvascular disease.

Association between PON 1 polymorphisms, PON activity and diabetes complications.

The paraoxonase (PON) gene cluster maps to human chromosome 7q21-22. In the PON 1 gene, several polymorphisms in the promoter and coding regions have been identified and are known to influence gene expression levels. Promoter polymorphisms have been shown to have the strongest influence on paraoxonase activity levels. Paraoxonase, a high-density lipoprotein associated enzyme, protects lipoproteins from oxidation. Lipid oxidation may play an important role in the development of micro- and macrovascular disease. There is evidence that paraoxonase activity is reduced in patients with diabetes. We therefore hypothesise that PON 1genotypes influence paraoxonase activity levels and increase the risk of microvascular disease in type 1 diabetes. Genotyping of 156 Caucasian adolescents with diabetes for seven PON 1 polymorphisms was performed, including that of a novel PON 1 promoter polymorphism A(-1074)G. PON genotypes were related to paraoxonase and arylesterase activities and diabetes complication status. There was strong linkage disequilibrium between the PON 1 promoter polymorphisms. Both promoter and coding region polymorphisms strongly influenced activity levels and were associated with diabetes complications. PON 1 genotypes Leu/Leu 54, AA(-162) and GG(-1074) were associated with higher urinary albumin loss, while the genotype GG(-907) was protective for retinopathy.