Search

OBJECTIVECurrent guidelines recommend biennial diabetic retinopathy (DR) screening commencing at the age of 11 years and after 2–5 years’ duration of type 1 diabetes. Growing evidence suggests less frequent screening may be feasible.RESEARCH DESIGN AND METHODSProspective data were collected from 2,063 youth with type 1 diabetes who were screened two or more times between 1990 and 2019. Baseline (mean ± SD) age was 13.3 ± 1.8 years, HbA1c was 8.6 ± 1.3% (70.1 ± 14.7 mmol/mol), diabetes duration was 5.6 ± 2.8 years, and follow-up time was 4.8 ± 2.8 years. DR was manually graded from 7-field retinal photographs using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Markov chain was used to calculate probabilities of DR change over time and hazard ratio (HR) of DR stage transition.RESULTSThe incidence of moderate nonproliferative DR (MNPDR) or worse was 8.6 per 1,000 patient-years. Probabilities of transition to this state after a 3-year interval were from no DR, 1.3%; from minimal DR, 5.1%; and from mild DR, 22.2%, respectively. HRs (95% CIs) for transition per 1% current HbA1c increase were 1.23 (1.16–1.31) from no DR to minimal NPDR, 1.12 (1.03–1.23) from minimal to mild NPDR, and 1.28 (1.13–1.46) from mild to MNPDR or worse. HbA1c alone explained 27% of the transitions between no retinopathy and MNPDR or worse. The addition of diabetes duration into the model increased this value to 31% (P = 0.03). Risk was also increased by female sex and higher attained age.CONCLUSIONSThese results support less frequent DR screening in youth with type 1 diabetes without DR and short duration. Although DR progression to advanced stages is generally slow, higher HbA1c greatly accelerates it.

Study Objective Coronavirus disease 2019 (COVID-19) infection poses significant risks during surgical interventions. We investigated the intraperitoneal presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients who are COVID-19 positive. Design A prospective group study. Setting Department of Obstetrics and Gynecology designated for patients with COVID-19, Central Clinical Hospital of the Ministry of Interior, Warsaw. Patients Overall, 65 pregnant women with COVID-19 infection underwent cesarian section. The diagnosis was confirmed either by positive antigen test or by positive reverse transcriptase-polymerase chain reaction assay performed within no more than 13 days before the operation. Interventions On the day of the operation, a nasopharyngeal swab was taken, and peritoneal fluid was collected at the beginning of the operation. Both the nasopharyngeal swab and peritoneal fluid samples were tested for SARS-CoV-2. Measurements and Main Results A total of 65 pregnant women with COVID-19 infection were enrolled in the study. The SARS-CoV-2 ribonucleic acid test by nasopharyngeal swab produced positive results in 34 patients. In this group as well as in 31 nonconfirmed patients, all peritoneal fluid samples tested negative for SARS-CoV-2 ribonucleic acid. Conclusion These results suggest a low risk of COVID-19 transmission from the peritoneal cavity at the time of laparoscopy or laparotomy.

The early prediction of health outcomes for people with diabetes mellitus is desirable, as are adjunct therapies to reduce the related chronic complications and risk of premature death. The length of telomeres, protective caps on chromosome ends, is influenced by genetic and acquired factors, and shorter telomeres have been associated with and predictive of adverse cardiometabolic outcomes. Many studies have shown associations between telomere length in white blood cells (WBC) and diabetes per se and its chronic complications, and some studies show that telomeres do not always progressively shorten in people with diabetes. With the pandemic of diabetes and taking into consideration the calculations of residual risk using existent risk equations, additional tests to stratify subject risk are desirable. In this evolving era of precision medicine for people with diabetes, this 'global biomarker' of WBC telomere length may be useful to help predict health outcomes, to monitor health status, and may be a therapeutic target. We comment on the field of telomere investigations in diabetes, including recommending areas for further clinical research.

The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n = 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p p p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (> 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend

Background: Mitochondrial DNA (Mt-DNA) copy number (mtDNA-CN) has been proposed as a marker of diabetic kidney disease (DKD) . Most studies are in type 2 diabetes. We determined mtDNA-CN in adults with type 1 diabetes vs. non-diabetic subjects, including associations with complications and risk factors. Methods: Cross-sectional study: 178 T1D adults (mean (SD) age: 38 (14) yrs, 21 (14) yrs T1D, HbA1c: 8.0 (1.5) %, 36% with complications (CX+)) ; 132 non-diabetic adults (CON) (age: 37 (14) yrs, HbA1c: 5.1 (0.4) %) . mtDNA-CN by RT-PCR (ScienCell, Carlsbad, CA) in DNA from whole blood samples. Results: T1D vs. CON: Median (LQ, UQ) mtDNA-CN in T1D vs. CON: 270.8 (189.4, 348.1) vs. 320.5 (264.4, 410.5) ; p Conclusion: T1D per se is associated with lower mtDNA-CN than CON, particularly with DKD. Higher mtDNA-CN in T1D is associated with detectable C-peptide. Age and inflammation related factors are associated with mtDNA-CN. Longitudinal and intervention studies are merited. Disclosure A.S.Januszewski: None. L.Carroll: None. Y.W.Loh: None. D.N.O'neal: None. A.Jenkins: Advisory Panel; Abbott Diabetes, Amgen Inc., Board Member; Insulin for Life , International Diabetes Federation Western Pacific Region, Research Support; JDRF, Medtronic, Mylan N.V., NHMRC Australia.

Diabetes is a major cause of vision loss globally, yet this devastating complication is largely preventable. Early detection and treatment of diabetic retinopathy necessitates screening. Ocular imaging is widely used clinically, both for the screening and management of diabetic retinopathy. Common eye conditions, such as glaucoma, cataracts and retinal vessel thrombosis, and signs of systemic conditions, such as hypertension, are frequently revealed. As well as imaging by a skilled clinician during an eye examination, non‐ophthalmic clinicians, such as general practitioners, endocrinologists, nurses and trained health workers, can also can carry out diabetic eye screening. This process usually comprises local imaging with remote grading, mostly human grading. However, grading incorporating artificial intelligence is emerging. In a clinical research context, retinal vasculature analyses using semi‐automated software in many populations have identified associations between retinal vessel geometry, such as vessel caliber, and the risk of diabetic retinopathy and other chronic complications of type 1 and type 2 diabetes. Similarly, evaluation of corneal nerves by corneal confocal microscopy is revealing diabetes‐related abnormalities, and associations with and predictive power for other chronic diabetes complications. As yet, the value of retinal vessel geometry and corneal confocal microscopy measures at an individual level is uncertain. In this article, targeting non‐ocular clinicians and researchers, we review existent and emerging ocular imaging and grading tools, including artificial intelligence, and their associations between ocular imaging findings and diabetes and its chronic complications., Investigating ocular imaging techniques for analyzing diabetic retinopathy and its complications.

For optimal diabetes management HbA1c, lipid and renal function measurements are key. Suitable point-of-care systems can provide such data in remote areas, diabetes camps, disaster relief, small community hospitals and in community screening days in disadvantaged regions. Some systems are currently used in Australian rural, remote and indigenous health services.

Aims To investigate whether long-term glycemic variability (GV) is associated with vascular complication development in type 2 diabetes. Methods In a post hoc FIELD trial analysis, GV was calculated as the standard deviation and coefficient of variation (CV) of glycated hemoglobin A1c (HbA1c) and fasting plasma glucose. Baseline variables were compared across quartiles of on-study variability by chi square and ANOVA. Prospective associations between baseline to 2-year GV and subsequent vascular and mortality outcomes were analyzed using landmark logistic and Cox proportional hazards regression. Results Baseline factors associated with higher on-study GV included younger age, male gender, longer diabetes duration, and higher pharmacological therapies usage. Both HbA1c and fasting glucose CV were associated with increased risk of microvascular complications (HR 1.02 [95% CI, 1.01-1.03] P < 0.01; and HR 1.01 [95% CI, 1.00-1.01] P < 0.001, respectively). HbA1c and fasting glucose CV were associated with increased cardiovascular disease (HR 1.02 [95% CI, 1.00-1.04]; and HR 1.01 [95% CI, 1.00-1.02], both P < 0.05). HbA1c CV associated with increased stroke (HR 1.03 [95% CI, 1.01-1.06) P < 0.01). Glucose CV associated with increased coronary events (HR 1.01 [95% CI, 1.00-1.02] P < 0.05). Both HbA1c and glucose CV associated with increased total mortality (HR 1.04 [95% CI, 1.02-1.06]; and HR 1.01 [95% CI, 1.01-1.02], both P < 0.001) and noncardiovascular mortality (HR 1.05 [95% CI, (1.03-1.07]; and HR 1.02 [95% CI, 1.01-1.03], both P < 0.001). HbA1c CV associated with coronary mortality (HR 1.04 [95% CI, 1.01-1.07] P < 0.05). Conclusions Long-term GV was associated with increased risk of vascular outcomes in type 2 diabetes.

Low insulin sensitivity (IS) increases Type 1 diabetes (T1D) complication risk and can be estimated by simple formulae developed from complex euglycemic hyperinsulinaemic clamp studies. We aimed to validate these formulae using independent clamp data.Clamps were performed in 104 T1D adults. Measured glucose disposal rate (GDR) was correlated with eGDR and eLog10 M/I calculated by five IS formulae.Correlations ranged between 0.23-0.40. Two IS formulae (by the authors), using age, sex, HDL-C, HbA1c, pulse pressure, BMI, and waist-hip-ratio had the highest correlation with measured GDR and the best performance in detecting low IS.

The diagnosis of atrophic gastritis (AG) and intestinal metaplasia (IM) is a crucial screening and surveillance strategy for gastric adenocarcinoma.The main objective was to assess the performance of endoscopic diagnosis of gastric precancerous conditions in a real‑life scenario.A total of 2099 gastroscopies with biopsy to evaluate gastritis performed in 3 endoscopic centers from March 2018 to October 2019 were retrospectively analyzed. Endoscopic data regarding gastritis, atrophy, and intestinal metaplasia were compared with histopathological reports.The endoscopic diagnosis sensitivity was 69.5% for AG and 19.4% for IM. The specificity of endoscopic detection of AG was 69.5% and of IM, 97.9%. The endoscopic detection of gastritis was a risk factor for AG and IM diagnosis (odds ratio [OR], 5.1; 95% CI, 1.9-14.1 and OR, 14.5; 95% CI, 5.9-35.8, respectively) and the patient's age was a risk factor for AG, IM, dysplasia, and advanced stage of AG (ASAG) diagnosis (OR, 1.05; 95% CI, 1.04-1.06; OR, 1.035; 95% CI, 1.03-1.04; OR, 1.04; 95% CI, 1.02-1.06; and OR, 1.05; 95% CI, 1.02-1.09, respectively). The age threshold of 45 or 40 years with endoscopically diagnosed gastritis for obtaining biopsy would result in 96.3% and 95% ASAG or dysplasia diagnosis sensitivity, and in the reduction of the number of biopsies by 20.2% and 20.5%, respectively.The application of the age threshold with or without an endoscopic diagnosis of gastritis could reduce the number of mapping biopsies to detect advanced stages of atrophic gastritis or dysplasia with high sensitivity.

We have analysed insulin antibodies in 149 adults with type 1 diabetes and 2859 people without diabetes. We have determined that insulin antibody levels are higher in adults with, versus without, diabetes and that the levels are falling, and more patients are becoming antibody-negative post islet cell transplantation.

People with diabetes are at risk of chronic complications and novel biomarkers, such as Advanced glycation end-products (AGEs) may help stratify this risk. We assessed whether plasma low-molecular weight AGEs, also known as LMW-fluorophores (LMW-F), are associated with risk factors, predict complications, and are altered by fenofibrate in adults with type 2 diabetes. Plasma LMW-F were quantified at baseline, after six weeks fenofibrate, and one year post-randomisation to fenofibrate or placebo. LMW-F associations with existing and new composite vascular complications were determined, and effects of fenofibrate assessed. LMW-F correlated positively with age, glycated haemoglobin (HbA1c), pulse pressure, kidney dysfunction and inflammation; and negatively with urate, body mass index, oxidative stress and leptin, albeit weakly (r = 0.04-0.16, all p

Understanding the mechanisms underlying the selective susceptibility to ischemia of the CA3 region is very important to explain the neuropathology of memory loss after brain ischemia. We used a rat model to study changes in gene expression of the amyloid protein precursor and its cleaving enzymes and tau protein in the hippocampal CA3 sector, after transient 10-min global brain ischemia with survival times of 2, 7, and 30 days. The expression of the α-secretase gene was below control values at all times studied. But, the expression of the β-secretase gene was below the control values at 2–7 days after ischemia and the maximal increase in its expression was observed on day 30. Expression of the presenilin 1 gene was significantly elevated above the control values at 2–7 days after ischemia and decreased below the control values at day 30. Expression of the presenilin 2 gene showed an opposite trend to the expression of presenilin 1. Expression of the amyloid protein precursor gene after ischemia was at all times above the control values with a huge significant overexpression on day 7. Additionally, the expression of the tau protein gene was below the control values 2 days after ischemia, but the significant increase in its expression was observed on days 7–30. Data show that brain ischemia activates neuronal changes and death in the CA3 region of the hippocampus in a manner dependent on amyloid and tau protein, thus determining a new and important way to regulate the survival and/or death of ischemic neurons.

To determine whether continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) therapy from near-diagnosis of type 1 diabetes is associated with reduced glycaemic variability (GV) and altered microRNA (miRNAs) expression. Adolescents (74% male) within 3-months of diabetes diagnosis (n = 27) were randomized to CSII (n = 12) or MDI. HbA1c, 1-5-Anhydroglucitol (1,5-AG), high sensitivity C-peptide and a custom TaqMan qPCR panel of 52 miRNAs were measured at baseline and follow-up (median (LQ-UQ); 535 (519–563) days). There were no significant differences between groups in baseline or follow-up HbA1c or C-peptide, nor baseline miRNAs. Mean ± SD 1,5-AG improved with CSII vs. MDI (3.1 ± 4.1 vs. − 2.2 ± − 7.0 mg/ml respectively, P = 0.029). On follow-up 11 miRNAs associated with diabetes vascular complications had altered expression in CSII-users. Early CSII vs. MDI use is associated with lower GV and less adverse vascular-related miRNAs. Relationships with future complications are of interest.

Objectives: Although the PARAGON-HF trial failed to reach its primary endpoint, subgroups of patients with heart failure with preserved ejection fraction (HFpEF) still appear to benefit from Sacubitril/Valsartan therapy. As HFpEF patients with pulmonary hypertension display a specifically high mortality and morbidity, we evaluated the effect of Sacubitril/Valsartan in this subgroup of HFpEF patients.Methods: In this retrospective case-series of 18 patients with HFpEF and pulmonary hypertension, right heart catheterisation (RHC) for determination of invasive pulmonary pressure were performed at baseline (pre-Sacubitril/Valsartan) and 99 (71–156) days after transition from angiotensin-converting enzyme inhibitors and angiotensin receptor blockers to Sacubitril/Valsartan (post-Sacubitril/Valsartan). Results are given as median and interquartile range.Results: After conversion to Sacubitril/Valsartan, RHC showed significantly reduced pulmonary artery pressure (PAP) and mean pulmonary capillary wedge pressure (PCWP) compared to pre-Sacubitril/Valsartan [PAP systolic/diastolic/mean 44 (38–55)/15 (11–20)/27 (23–33) mm Hg vs. 51 (41–82)/22 (13–29)/33 (28–52) mm Hg, p < 0.05 and p < 0.01, respectively; PCWP 16 (12–20) mm Hg vs. 22 (15–27) mm Hg, p < 0.05]. Median Sacubitril/Valsartan dosage was 24/26 mg BID (24/26 BID−49/51 mg BID). Clinically, New York Heart Association functional class improved in 12 of the 18 patients (p < 0.01) after conversion to Sacubitril/Valsartan. Echocardiographic parameters of left ventricular function and cardiovascular co-medication did not differ markedly between pre- and post-Sacubitril/Valsartan.Conclusion: Sacubitril/Valsartan therapy is associated with an improvement of pulmonary hypertension in HFpEF patients.

Introduction: Excess adipose tissue, esp. with the metabolic syndrome (MetS) promotes development of type 2 diabetes (T2D) and cardiovascular disease (CVD). A major feature of MetS, reduced insulin sensitivity (IS), is associated with increased hepatic lipogenesis, a marker of which is a low SHBG. Features of T2D are increasingly common in T1D. Aim: In T1D adults to determine if SHBG is associated with surrogate measures of IS and MetS. Methods: Cross-sectional analysis of sera from 279 people (Table). Of those with T1D 41 had microvascular complications. SHBG was quantified by chemiluminescent immunoassay (Roche Diagnostics, Mannheim, Germany). IS in T1D was assessed by estimation of M/I by modified published formulae using sex, HDL-C, pulse pressure, T1D duration, waist/height, WHR, BMI and HbA1c. Results: SHBG levels were higher in T1D than in CON and also higher in F vs. M. SHBG levels correlated with age in CON and T1D. M/I in tertile 3 (sex and T1D adjusted) of SHBG was significantly higher vs. tertiles 1 and 2 (in CON and T1D). In T1D SHBG (age and sex adjusted) decreased with increasing number of MetS features. ROC curve for MetS diagnosis in T1D using SHBG had an AUC of 0.73. Conclusion: Taken together these data show that IS and MetS are associated with lower SHBG levels in T1D. We propose a role for SHBG in personalising insulin sensitiser treatment in T1D. Disclosure A. S. Januszewski: None. W. Rankin: None. D. N. O9neal: Advisory Panel; Self; Abbott Diabetes, Medtronic, Sanofi, Research Support; Self; Dexcom, Inc., GlySens Incorporated, Medtronic, Pacific Diabetes Technologies. G. A. Wittert: Advisory Panel; Self; Bayer AG, Research Support; Self; Bayer AG, Speaker9s Bureau; Self; Bayer AG. A. Jenkins: Advisory Panel; Self; Abbott Diabetes, Sanofi-Aventis, Other Relationship; Self; Amgen Inc., Research Support; Self; Abbott, International Diabetes Federation, JDRF, Medtronic, Mylan N. V.

Introduction: The “gold standard” measure of insulin sensitivity (IS), a euglycemic hyperinsulinemic clamp, is costly, time- and labour-intensive. Several formulae, developed using clamp data estimate insulin sensitivity, expressed as estimated glucose disposal rate (eGDR) or insulin sensitivity index (eM/I or elog10M/I). Due to clamp complexity and cost these formulae often lacks independent validation. Aim: To validate several formulae estimating IS using independent euglycaemic hyperinsulinemic clamp data. Methods: Euglycemic, hyperinsulinemic clamps were performed in 108 T1D adults (age (mean±SD) 34±7 yrs, T1D duration 10±4 yrs, HbA1c 7.7±1.5%; 33 with microvascular complications). Measured GDR (last 30min of the clamp) ranged 0.5 - 9.6 mg/kg/min (median (LQ, UQ) 4.45 (3.04, 6.5 mg/kg/min) were compared with eGDR and eLog10M/I calculated using simple formulae by (1) Williams, (2) Zheng, (3) Dabelea and (4) and (5) (Australia (AU)) authors, all derived from routine clinical chemistry and demographics. eGDR formula (Duca) was not assessed as it includes adiponectin levels. Results: Results are in Table 1. Conclusion: Authors (AU) formulae to estimate IS, including age, sex, HDL-C, BMI, HbA1c, pulse pressure and WHR had highest correlation with measured GDR and better performance (AUROC) in detecting low IS than other formulae. Disclosure A. S. Januszewski: None. P. Niedzwiecki: None. N. Sachithanandan: None. G. M. Ward: None. C. Karschimkus: None. D. N. O’neal: Advisory Panel; Self; Abbott Diabetes, Medtronic, Sanofi, Research Support; Self; Dexcom, Inc., GlySens Incorporated, Medtronic, Pacific Diabetes Technologies. D. Zozulinska-ziolkiewicz: None. A. Uruska: None. A. Jenkins: Advisory Panel; Self; Abbott Diabetes, Sanofi-Aventis, Other Relationship; Self; Amgen Inc., Research Support; Self; Abbott, International Diabetes Federation, JDRF, Medtronic, Mylan N. V.

Funding Acknowledgements Type of funding sources: None. Introduction Left ventricular assist device (LVAD) is an expanding therapy in end-stage heart failure today. Although LVAD therapy bears the potential to normalize cardiac output, a majority of patients show a severely impaired physical condition at the time of LVAD implantation. To date, no validated standardized training protocol is available, and established practices to effectively improve LVAD patients’ exercise tolerance is lacking. This study sought to investigate exercise capacity quantified by cardiopulmonary exercise testing (CPX) and a standardized six-minute walk test (6MWT) in patients after LVAD implantation. Methods We enrolled 30 end-stage heart failure patients who had received an LVAD implantation 20.7 ± 7.6 days prior to examination, mean age 54.9 ± 7.8 years, 26 males (87 %). Exercise tolerance was assessed using cardiopulmonary exercise testing (CPX) for maximal and submaximal exercise capacity, followed by a standardized (6MWT). Results Patients showed peak oxygen uptake values of 8.3 ± 2.4 ml/min/kg at a mean workload of 46.7 ± 11.3 watts and a mean anaerobic threshold of 6.7 ± 1.7 ml/min/kg at a workload of 32.6 ± 6.9 watts. Mean standardized 6-minute walking distance was at 183.8 ± 71.4 meters. There were no adverse events during exercise testing. Conclusions Cardiopulmonary exercise testing (CPX) and standardized 6MWT show severely impaired cardiopulmonary exercise capacity in patients after LVAD implantation, warranting further studies for dedicated training protocols, specifically focusing on LVAD patients to improve exercise tolerance at an acceptable safety profile.

Aims We aimed to determine how white blood cell (WBC) telomeres and telomere length change over time are associated with health status in type 1 diabetes. Methods Relative telomere length (rTL) was measured in WBC DNA from two time-points (median 6.8 years apart) in 618 individuals from the Finnish Diabetic Nephropathy Study by quantitative PCR, with interassay CV ≤ 4%. Results Baseline rTL correlated inversely with age and was shorter in men. Individuals in the shortest vs. longest rTL tertile had adverse cardiometabolic profiles, worse renal function, and were prescribed more antihypertensive and lipid-lowering drugs. While overall rTL tended to decrease during the median 6.8-years of follow-up, telomeres shortened in 55.3% of subjects, lengthened in 40.0%, and did not change in 4.7%. Baseline rTL correlated inversely with rTL change. Telomere lengthening was associated with higher HDL-Cholesterol (HDL-C), HDL-C/ApoA1, and with antihypertensive drug and (inversely) with lipid-lowering drug commencement during follow-up. Correlates of rTL percentage change per-annum (adjusted model) were baseline BMI, eGFR, previous retinal laser treatment, HDL-C, and HDL-C/ApoA1. Conclusions Telomere length measurements may facilitate the treatment and monitoring of the health status of individuals with type 1 diabetes.

Background Esophagogastroduodenoscopy (EGD) is commonly used diagnostic method with no widely accepted quality measure. We assessed quality indicator—composite detection rate (CDR)—consisting of detection of at least one of the following: cervical inlet patch, gastric polyp and post-ulcer duodenal bulb deformation. The aim of the study was to validate CDR according to detection rate of upper gastrointestinal neoplasms (UGN). Methods It was a multicenter, prospective, observational study conducted from January 2019 to October 2019. The endoscopic reports from 2896 symptomatic patients who underwent diagnostic EGD were analyzed. The EGDs were performed in three endoscopy units located in tertiary university hospital, private outpatient clinic and local hospital. Results 64 UGNs were detected. The mean CDR was 21.9%. The CDR correlated with UGN detection rate (R = 0.49, p = 0.045). Based on CDR quartiles, operators were divided into group 1 with CDR 26%. Detection rate of UGN was significantly higher in the group 4 in comparison to group 1 (OR 4.4; 95% CI 2.2 − 9.0). In the multivariate regression model, patient age, male gender and operator’s CDR > 26% were independent risk factors of UGN detection (OR 1.03; 95% CI 1.01 − 1.05, OR 2; 95% CI 1.2 − 3.5, and OR 5.7 95% CI 1.5 − 22.3, respectively). Conclusions The CDR is associated with the detection of upper gastrointestinal neoplasms. This parameter may be a useful quality measure of EGD to be applied in general setting.

Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). As disturbed angiogenesis and endothelial dysfunction are strongly implicated in T2D and CVD, we aimed to investigate the association between a novel anti-angiogenic protein, FK506-binding protein like (FKBPL), and these diseases. Plasma FKBPL was quantified by ELISA cross-sectionally in 353 adults, consisting of 234 T2D and 119 non–diabetic subjects with/without CVD, matched for age, BMI and gender. FKBPL levels were higher in T2D (adjusted mean: 2.03 ng/ml ± 0.90 SD) vs. non-diabetic subjects (adjusted mean: 1.79 ng/ml ± 0.89 SD, p = 0.02), but only after adjustment for CVD status. In T2D, FKBPL was negatively correlated with fasting blood glucose, HbA1c and diastolic blood pressure (DBP), and positively correlated with age, known diabetes duration, waist/hip ratio, urinary albumin/creatinine ratio (ACR) and fasting C-peptide. FKBPL plasma concentrations were increased in the presence of CVD, but only in the non-diabetic group (CVD: 2.02 ng/ml ± 0.75 SD vs. no CVD: 1.68 ng/ml ± 0.79 SD, p = 0.02). In non-diabetic subjects, FKBPL was positively correlated with an established biomarker for CVD, B-type Natriuretic Peptide (BNP), and echocardiographic parameters of diastolic dysfunction. FKBPL was a determinant of CVD in the non-diabetic group in addition to age, gender, total-cholesterol and systolic blood pressure (SBP). FKBPL may be a useful anti-angiogenic biomarker in CVD in the absence of diabetes and could represent a novel CVD mechanism.

AIM: To measure skin autofluorescence in youth (

Telomeres are regions of repetitive nucleotide sequences at the ends of chromosomes. Telomere length is a marker of DNA damage, which is often considered a biomarker for biological ageing, and has also been linked with cardiovascular disease, diabetes, and cancer. Emerging studies have highlighted the role of genetic and environmental factors, and explored the effect of modulating telomere length. We provide an overview of studies to date on diabetes and telomere length, and compare different methods and assays for evaluating telomere length and telomerase activity. We highlight the limitations of current studies and areas that warrant further research to unravel the link between diabetes and telomere length. The value of adding telomere length to clinical risk factors to improve risk prediction of diabetes and related complications also merits further investigation.

Introduction: Current ISPAD guidelines recommend biennial diabetic retinopathy (DR) screening starting at age 11 yrs with type 1 diabetes (T1D) duration 2-5 yrs. Growing evidence suggesting less frequent screening. Methods: DR was ETDRS graded and progress assed by Markov chain model analysis. Retinal photos were from 2,169 patients (baseline (mean±SD): age 13.1±2.1 yrs, HbA1c 8.5±1.4%, 5.4±2.9 yrs T1D, follow-up 5.3±3.6 yrs) who attended the T1D clinic at least twice in 1990-2018. Results: In 11/2,169 patients DR progressed to severe non-proliferative (SNP) DR or above. See tables 1 and 2 below for detailed results. Conclusions: Our data support less frequent DR screening in T1D youth without any DR. Although DR progression is generally slow, poor glycaemic control greatly accelerates it. Disclosure A.S. Januszewski: None. V. Velayutham: None. P.Z. Benitez-Aguirre: None. M.E. Craig: None. G. Liew: None. Y. Cho: None. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. K.C. Donaghue: None.

Background There is a global concern that physician-researchers are 'a dying breed'. Recent studies of clinical career choices of Australian medical students and doctors have signalled the rising age of medical graduates, generational shifts in work-life attitudes and increased proportion of female graduates. There are scant data regarding Australian physician-researchers. Aims To develop and utilise a questionnaire determining respondent characteristics and 'push' and 'pull' factors for medical graduates to incorporate research into their careers. Methods We developed and administered an 88-item online survey, including quantitative and qualitative questions, to medical students, faculty and alumni of Sydney Medical School, The University of Sydney, asking about their medical career, research experience and interest and reasons for doing or not doing medical research. Responses to all 74 quantitative questions are reported here. Results Data from 427 respondents (44% female; mean ± standard deviation age 38 ± 13 years; 56% completed or undertaking a PhD) were analysed. Attractions of research included a desire to improve human health, intellectual stimulation and career diversity. Barriers included low funding rates, job insecurity and low salaries. Although few were prepared to undertake or recommend full-time research, 71% would recommend part-time research. Respondents perceived a smaller-than-actual gap between clinical and research salaries, and if comparable (75-100% of a clinician's) salaries were available, 89% would like to spend 21-60% of their work time undertaking research. Conclusion Many Australian medical students and doctors are interested in research, especially part time. Perceived obstacles include job insecurity, low funding rates and salary. Respondents underestimated clinical and research salary differences.

To evaluate the risk algorithm by Aspelund et al. for predicting sight-threatening diabetic retinopathy (STDR) in Type 2 diabetes (T2D), and to develop a new STDR prediction model.The Aspelund et al. algorithm was used to calculate STDR risk from baseline variables in 1012 participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) ophthalmological substudy, compared to on-trial STDR status, and receiver operating characteristic analysis performed. Using multivariable logistic regression, traditional risk factors and fenofibrate allocation as STDR predictors were evaluated, with bootstrap-based optimism-adjusted estimates of predictive performance calculated.STDR developed in 28 participants. The Aspelund et al. algorithm predicted STDR at 2- and 5-years with area under the curve (AUC) 0.86 (95% CI 0.77-0.94) and 0.86 (0.81-0.92), respectively. In the second model STDR risk factors were any DR at baseline (OR 24.0 [95% CI 5.53-104]), HbA1c (OR 1.95 [1.43-2.64]) and male sex (OR 4.34 [1.32-14.3]), while fenofibrate (OR 0.13 [0.05-0.38]) was protective. This model had excellent discriminatory ability (AUC = 0.89).The algorithm by Aspelund et al. predicts STDR well in the FIELD ophthalmology substudy. Logistic regression analysis found DR at baseline, male sex, and HbA1c were predictive of STDR and, fenofibrate was protective.

BACKGROUND: In people with type 1 diabetes (T1D), nocturnal hypoglycaemia (NH) can be slept through and can cause seizures, arrhythmias and death. Hypoglycaemia avoidance can induce hyperglycaemia and ketosis. Patient behaviour impacts clinical outcomes and may be changed by education. AIM: To develop and utilise a survey to evaluate patient self-management of overnight glycaemia in adults with T1D. METHODS: Adults with T1D attending two Australian tertiary referral diabetes clinics completed a survey about their diabetes self-management and glycaemic control, including responses to hypothetical pre-bed blood glucose (BG) levels (4-20 mmol/L). Statistical analyses included t-tests, Chi square tests and ANOVA with significance considered at P < 0.05. RESULTS: There were 205 participants (103 females), with a mean (SD) age of 41 (17) years, T1D duration of 20 (16) years, HbA1c of 7.8(1.4)%, (61.3(8.2) mmol/mol), 38% on insulin pump therapy (CSII) and 36% with impaired hypoglycaemia awareness (IHA). Mean (SD) number of BG tests/day was 5.4 (2.7). Patients set higher BG target levels at bedtime and overnight: 7.5(1.4) and 7.1(1.3) mmol/L, respectively, compared to daytime (6.9(1.0); P < 0.0001 and P = 0.002 respectively). Only 36% of participants reported treating nocturnal hypoglycaemia (NH) with the recommended refined, then complex, carbohydrate. Only 28% of patients made safe choices in all bedtime BG scenarios, with higher rates for CSII users, P = 0.0005. Further education was desired by 32% of respondents, with higher rates in those with (44%) versus without IHA (25%), P = 0.006. CONCLUSIONS: Many adults with T1D have suboptimal knowledge and behaviour regarding overnight BG self-management. A survey, piloted herein, may facilitate the identification of patients who could benefit from further education.

Objectives: The optimal blood glucose target in critically ill patients with preexisting diabetes and chronic hyperglycemia is unknown. In such patients, we aimed to determine whether a“liberal” approach to glycemic control would reduce hypoglycemia and glycemic variability and appear safe. Design: Prospective, open-label, sequential-period exploratory study Setting: Medical-surgical ICU. Patients: During sequential 6-month periods, we studied 83 patients with preexisting type 2 diabetes and chronic hyperglycemia (glycated hemoglobin, ≥ 7.0% at ICU admission). Intervention: During the “standard care” period, 52 patients received insulin to treat blood glucose concentrations greater than 10 mmol/L whereas during the “liberal” period, 31 patients received insulin to treat blood glucose concentrations greater than 14 mmol/L. Measurements and Main Results: Time-weighted mean glucose concentrations and the number and duration of moderate(< 4.0 mmol/L) and severe (≤ 2.2 mmol/L) hypoglycemic episodes were recorded, with moderate and severe hypoglycemic episodes grouped together. Glycemic variability was assessed by calculating the coefficient of variability for each patient. Safety was evaluated using clinical outcomes and plasma concentrations of markers of inflammation, glucose-turnover, and oxidative stress. Mean glucose (TW glucoseday 0–7, standard care: 9.3 [1.8]vs liberal: 10.3 [2.1] mmol/L; p = 0.02) and nadir blood glucose(4.4 [1.5] vs 5.5 [1.6] mmol/L; p < 0.01) were increased during the liberal period. There was a signal toward reduced risk of moderate-severe hypoglycemia (relative risk: liberal compared with standard care: 0.47 [95% CI, 0.19–1.13]; p = 0.09). Ten patients (19%) during the standard period and one patient (3%)during the liberal period had recurrent episodes of moderate severe hypoglycemia. Liberal therapy reduced glycemic variability (coefficient of variability, 33.2% [12.9%] vs 23.8% [7.7%];p < 0.01). Biomarker data and clinical outcomes were similar Conclusions: In critically ill patients with type 2 diabetes and chronic hyperglycaemia, liberal glycemic control appears to attenuate glycemic variability and may reduce the prevalence of moderate-severe hypoglycemia usc Refereed/Peer-reviewed

To examine the trajectory of small artery elasticity (SAE) and pulse pressure (PP) in people with Type 1 diabetes and non-diabetic controls across the lifespan, and explore associations with microvascular complications (CX+).This cross-sectional study included 477 Type 1 diabetes patients (188 with CX+, 289 without CX-) and 515 controls. Relationships between SAE and PP and age were evaluated using segmented linear regression. Logistic regression was used to assess the associations between microvascular complications (retinopathy and/or nephropathy) and SAE and PP.SAE peaked significantly later among controls than diabetic patients CX- vs. CX+ (21.2 vs. 20.4 vs. 17.6 years respectively, p 0.001). In adults, mean SAE was significantly lower in CX+ vs. CX- vs. controls (6.8 vs. 7.8 vs. 8.0 ml/mm Hg × 10; p 0.0001), and mean PP was significantly higher in CX+ vs CX- and controls (60 vs. 55 vs. 53 mm Hg; p 0.0001).Type 1 diabetes CX+ subjects have an earlier peak and decline in SAE relative to CX- and controls, who did not differ. Lower SAE and higher PP were associated with increased odds of Type 1 diabetes complications in adults. These clinically applicable techniques demonstrate an association between accelerated vascular aging and vascular complications in diabetes.

BACKGROUND It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associated with glycemic progression in patients with established type 2 diabetes. This study reports this relationship in type 2 diabetes patients participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. METHODS Plasma FGF21 was quantified in 9697 study participants. Among patients with lifestyle-only glucose control measures at baseline, glycemic progression was defined as the initiation of oral hypoglycemic agents or insulin therapy. We assessed the relationship of FGF21 concentrations with glycohemoglobin (Hb A1c), the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycemic progression. RESULTS Among 2584 patients with lifestyle-only glycemic therapy at baseline, plasma FGF21 concentrations were positively associated with HOMA-IR (5.1% increase per 100% increase in FGF21 concentrations). Patients with higher baseline plasma FGF21 concentrations had higher risk of glycemic progression over a 5-year period (P = 0.02), but the association was not significant after further adjusting for alanine aminotransferase (ALT) enzyme activity. During the fenofibrate active run-in phase, higher tertiles of fenofibrate-induced increase in FGF21 concentrations were associated with higher risk of glycemic progression (adjusted hazards ratio = 1.09 and 1.18 for tertiles 2 and 3, respectively, P for trend = 0.01), even after adjusting for ALT enzyme activity. This association was statistically significant in the fenofibrate group only (P = 0.01). CONCLUSIONS Higher baseline and fenofibrate-induced increase in FGF21 concentrations predict more rapid glycemic progression in type 2 diabetes patients. This association may be partly explained by hepatic function.

Background: In the FIELD trial, a 5-year randomized double-blind placebo-controlled trial of fenofibrate vs. placebo in 9,795 adults with type 2 diabetes (T2D), the only standard lipid parameter correlating with microvascular (renal) events was triglycerides. Given the high prevalence of stroke among diabetic patients, we explored associations between lipoprotein subfractions and risk for stroke in the FIELD trial. Methods: We performed ultracentrifugation using the vertical auto profile (VAP, Atherotech) on plasma (baseline and after 6 weeks of fenofibrate). Analyses were performed using Cox proportional hazards and logistic regression for new on-study events. Results were adjusted for gender and fenofibrate or placebo allocation. Results: HDL related analytes (HDL-C, HDL3-C, apo A1, apoA2) correlated with reduced risk for all stroke. LDL and its subfractions and Lp(a)-C did not. VLDL and its subfractions, non-HDL-C, triglycerides, apo B, apo En, various ratios incorporating apo C3, and the ratios of apoB/A1 and apoB/apoA2 all correlated with increased risk for stroke. Conclusions: VAP identifies multiple lipoprotein subclasses, apoproteins, and VAP subclass/apoprotein ratios associated with stroke. Many of these measures improved with fenofibrate therapy.

Insulin resistance in people with type 1 diabetes (T1D) is associated with increased risk of chronic complications and death. The gold standard to quantify insulin sensitivity, a euglycaemic hyperinsulinaemic clamp, is not applicable to clinical practice. We have employed clamp studies to develop a panel of formulae to estimate insulin sensitivity in adults with T1D for use in clinical practice and trials.Clamps were conducted in 28 adults with T1D, who were also characterised with 38 clinical and research biomarkers. Exhaustive search analysis was used to derive equations correlating with clamp-quantified glucose disposal rate (GDR), GDR/plasma insulin (M/I) and logMeasured insulin sensitivity correlated with BMI, WHR, HDL-C, adipokines and inflammation markers on univariate analysis. Exhaustive search analysis derived three formulae correlating with clamp-derived GDR and logM/I (p 0.0001), accounting for ≈62% of their variability. A formula using gender, age, HDL-C, pulse pressure and WHR performed as well as those containing inflammation and adipokine measures.The performance of formulae using routinely available parameters with/without research biomarkers in clinical studies and trials, particularly related to future complications, relevant lifestyle interventions, insulin delivery modes and insulin sensitisers is merited.

ObjectiveTo determine if continuous subcutaneous insulin infusion (CSII) therapy is associated with lower glycated haemoglobin (HbA1c) variability (long-term glycaemic variability; GV) relative to multiple daily injection (MDI) treatment in adults with type 1 diabetes mellitus (T1DM).DesignRetrospective audit.Setting and participantsClinic records from 506 adults with T1DM from two tertiary Australian hospitals.Outcome measuresLong-term GV was assessed by HbA1c SD and coefficient of variation (CV) in adults on established MDI or CSII therapy, and in a subset changing from MDI to CSII.ResultsAdults (n=506, (164 CSII), 50% women, mean±SD age 38.0±15.3 years, 17.0±13.7 years diabetes, mean HbA1c 7.8%±1.2% (62±13 mmol/mol) on CSII, 8.0%±1.5% (64±16 mmol/mol) on MDI) were followed for 4.1±3.6 years. CSII use was associated with lower GV (HbA1c SD: CSII vs MDI 0.5%±0.41% (6±6 mmol/mol) vs 0.7%±0.7% (9±8 mmol/mol)) and CV: CSII vs MDI 6.7%±4.6% (10±10 mmol/mol) vs 9.3%±7.3% (14±13 mmol/mol), both pConclusionsIn clinical practice with T1DM adults relative to MDI, CSII therapy is associated with lower HbA1c GV.

ContextSex hormone–binding globulin (SHBG) levels are associated with cardiovascular disease (CVD) risk factors. However, prospective data on the association between SHBG levels and CVD events are sparse, with conflicting results.ObjectivesTo examine associations between serum SHBG, total testosterone (TT), and incident CVD and CVD-related mortality in middle-aged to elderly men.Design and MethodsData on 2563 community-dwelling men (35 to 80 years) were obtained from participants in the Men Androgen Inflammation Lifestyle Environment and Stress cohort. The analytic sample included 1492 men without baseline (2002 to 2007) CVD and with fasted morning serum SHBG and TT available at both baseline and follow-up (2007 to 2010) and without medications affecting TT or SHBG. Associations of baseline SHBG and TT, with incident CVD and CVD mortality, were analyzed using logistic regression for incident CVD and Cox proportional hazard regression for CVD mortality, adjusting for established CVD risk factors.ResultsIn multivariable models, elevated baseline SHBG and lower baseline TT were independently associated with incident CVD (SHBG: OR, 1.54; 95% CI, 1.15 to 2.06 per SD increase in SHBG, P = 0.003; TT: OR, 0.71; 95% CI, 0.52 to 0.97 per SD decrease in TT; P = 0.03). A decrease in TT between time points was associated with incident CVD (OR, 0.72; 95% CI, 0.56 to 0.92; P = 0.01). Neither SHBG nor TT was significantly associated with all-age CVD mortality [hazard ratio (HR), 0.69; 95% CI, 0.29 to 1.63; P = 0.40; and HR, 0.60; 95% CI, 0.28 to 1.26; P = 0.18, respectively].ConclusionsAmong all men and men >65 years, elevated SHBG and lower TT were independently associated with both a greater risk of CVD and an increased CVD mortality risk.

Aim: Current guidelines recommend screening for retinopathy from 11 years in youth with type 1 diabetes (T1D) and 2-5 years T1D duration. We examined the longitudinal progression and regression of retinopathy in adolescents seen at our Diabetes Complications assessment service (DCAS) clinic. Methods: We analyzed digitized retinal photographs taken from 2000-2018 (n=814) in youth with >3 assessments. Retinopathy was graded using the modified Airlie house classification. Generalized estimating equations were used to explore the association between progression/regression and covariates (HbA1c, gender, and diabetes duration). Results: Mean age at baseline was 13.3+2.6 years, mean T1D duration 6.1+>3.4 years and mean follow- up 7.4 years. Retinopathy was present in 18.7% (n=152) at baseline assessment; with progression in 32.6% (n=266), regression in 7% (n=57) and persistence in 60.3% (n=491). Of those with progression, 185/266 (22.7%) had one step and 81 (9.9%) had > 2 step progression. Factors associated with retinopathy progression were HbA1c and T1D duration and for regression T1D duration (Table 1). Neither height nor SBP was significant for other outcomes. Conclusion: In adolescents with T1D, retinopathy persistence or progression was greater than of regression. Follow-up of into adulthood will inform the development of appropriate retinopathy screening schedules. Disclosure V. Velayutham: None. G. Liew: None. A.S. Januszewski: None. Y. Cho: None. P.Z. Benitez-Aguirre: None. M.E. Craig: None. A. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. K.C. Donaghue: None.

Background: Haptoglobin (Hp) is a plasma protein with anti-oxidant, anti-inflammatory and pro-angiogenic properties. Based on the Hp gene alleles there are three Hp phenotypes (1-1, 2-1 and 2-2). In diabetes, Hp-2 is associated with substantially increased risk of cardiac and renal damage relative to Hp-1. AIMS: To evaluate 1) associations between Hp phenotype and levels; and 2) effects of fenofibrate vs. placebo on Hp levels. Methods: A substudy of 180 adults with type 2 diabetes (T2D) (50% females) from the FIELD trial. Average age was 60±6 years, BMI 30.4±5.1 kg/m2 and HbA1c 6.8±1.3%. Plasma (citrate) samples were evaluated at baseline, after 6-weeks daily 200 mg co-micronised fenofibrate (end of active run-in) and 2-years after randomisation to fenofibrate or placebo. Results: Hp phenotype 1-1 was detected in 19%, Hp 2-1 in 48% and Hp 2-2 in 33% subjects. Hp levels at baseline were 1.44±1.10, 1.31±0.49 and 0.99±0.46 mg/mL in type 1-1, 2-1 and 2-2 respectively (all p Conclusions: Hp levels differ by Hp phenotype in T2D adults. Fenofibrate lowers Hp levels in all phenotypes, however the effect is significantly attenuated in Hp 2-2. Disclosure A.S. Januszewski: None. H.K. Young: Other Relationship; Self; Medtronic. L. Li: None. R.L. OConnell: None. T. Lyons: None. C.B. Kelly: None. D. Sullivan: None. R. Scott: None. A.C. Keech: None. A. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. Funding Sydney Medical School Foundation; National Health and Medical Research Council of Australia

Background: Fenofibrate increases renal clearance of uric acid (UA). Relationships between baseline and short-term changes in plasma UA with fenofibrate and subsequent cardiovascular risk in patients with type 2 diabetes (T2D) are unknown. Method: Post hoc analyses of the FIELD trial explored the relationships between CVD events and 1) baseline UA level; and 2) short-term change in UA level over 6-week single-blind active fenofibrate run-in. Results: The FIELD trial showed 11% fewer cardiovascular events in patients with T2D assigned to fenofibrate compared to placebo over 5 years (HR = 0.89, 95% CI: 0.80-0.99, p = 0.035). Baseline UA (n=9622) ranged between 0.11 to 0.79 mmol/L (mean = 0.33, SD = 0.078). Each 0.1 mmol/L higher baseline UA increased CVD events by 21% (HR = 1.21 95% CI: 1.13-1.29, p < 0.001; Fig. 1A), and remained after adjusting for other classic risk factors (HR = 1.12, 95% CI: 1.04-1.21, p = 0.002). Fall in UA level with fenofibrate run-in also predicted lower CVD risk, adjusted for baseline UA and irrespective of trial treatment allocation (HR = 0.86, 95% CI: 0.76-0.97, p = 0.015; Fig. 1B). Discussion: Baseline and short-term fenofibrate-induced lowering of UA predict cardiovascular risk in patients with T2D, irrespective of long-term trial treatment allocation. The reduction in total CVD events with fenofibrate was not shown to be mediated through lowering of UA levels. Disclosure J.Y. Cao: None. B. Waldman: None. R.L. OConnell: None. D. Sullivan: None. V. Gebski: None. A.S. Januszewski: None. I. Marschner: None. R. Scott: None. M. Taskinen: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Akcea Therapeutics, Chiesi USA, Inc. Research Support; Self; Amgen Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; Amgen Inc. R. Simes: None. N. McGill: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.C. Keech: None.

Background: In the FIELD trial, a 5-year randomized double-blind placebo-controlled trial of fenofibrate vs. placebo in 9,795 adults with type 2 diabetes (T2D), the only standard lipid parameter correlating with microvascular (renal) events was triglycerides. Given the high prevalence of diabetic microangiopathy, we explored associations between lipoprotein subfractions and nephropathy, retinopathy, microvascular amputations (MiAmp) and neuropathy. Methods: We performed ultracentrifugation using the vertical autoprofile (VAP, Atherotech) on plasma (baseline and after 6 weeks of fenofibrate). Analyses were performed using Cox proportional hazards and logistic regression for new on-study events. Results were adjusted for gender and fenofibrate or placebo allocation. Results: HDL related analytes (HDL-C, HDL3-C, apo A1, apoA2) correlated with reduced risk for neuropathy, nephropathy, and MiAmp. Buoyant LDL (LDL1-C) and densest LDL (LDL4-C) correlated negatively with neuropathy and positively for MiAmp, respectively. Triglycerides and apo C3 increased neuropathy and nephropathy risk. VLDL species correlated with increased MiAmp and retinopathy risk. Conclusions: VAP identifies multiple lipoprotein subclasses and VAP subclass/apoprotein ratios associated with diabetic microangiopathy. Many were improved with fenofibrate. Disclosure P.P. Toth: Consultant; Self; Amarin Corporation, Amgen Inc., AstraZeneca, Kowa Pharmaceutical Europe Co. Ltd., Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Amgen Inc., Merck & Co., Inc., Novo Nordisk Inc., Regeneron Pharmaceuticals, Sanofi US. A.C. Keech: None. A.S. Januszewski: None. R.L. OConnell: None. L. Li: None. D. Sullivan: None. M. Taskinen: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Akcea Therapeutics, Chiesi USA, Inc. Research Support; Self; Amgen Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; Amgen Inc. P.L. Drury: None. G.F. Watts: None. J.D. Best: Consultant; Self; Abbott. J. Ansquer: Research Support; Self; Abbott, Mylan. S.R. Jones: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.

Background: Glucose variability (GV) may be reflected by variation in either the short-term glucose levels (assessed by continuous glucose monitoring (CGM)) or the long-term by HbA1c or intermediate by 1,5-anhydroglucitol (1,5-AG). In patients with T1DM management by continuous subcutaneous insulin infusion (CSII) is usually associated with improved glycaemia compared to multiple daily insulin injections (MDI). Serum 1,5-anhydroglucitol (1,5-AG) correlates with GV on CGM in adult and pediatric T1D groups. It is not known whether CSII therapy without CGM improves intermediate GV. Methods: Blood was obtained from children (mean age 14.1 +/- 1.3 years) within 3-months of T1D diagnosis. Children were treated with CSII (n=12) or MDI (n=15) and followed for a further 1 to 3 time points (median, LQ-UQ 535, 519-563 days follow-up). GV was assessed measuring 1,5-anhydroglucitol (1,5-AG) (GlycoMark, Inc., Winston-Salem, NC). The mean difference, standard deviation (SD) and coefficient of variation (CV) of 1,5-AG and HbA1c was compared between treatment arms. Results: There was no difference between treatment modalities in baseline HbA1c (median, LQ-UQ 11.8, 10.2-13.5 % (105, 87-124 mmol/mol) vs. 12.6, 10.3-14.0 % (114, 89-130 mmol/mol) CSII vs. MDI) nor baseline 1,5-AG (median, LQ-UQ 2.8, 1.8-4.0 μg/mL vs. 3.6, 2.1-12.1 μg/mL CSII vs. MDI). 1,5-AG improved more (increased) in the CSII vs. MDI group (3.1 +/- 4.1 vs. -2.2 +/- 7.0 μg/ml respectively, P=0.029). This difference persisted following adjustment for the duration of follow-up. There was no significant difference in the HbA1c improvement between the CSII and MDI groups. There was no significant difference in the SD or CV of 1,5-AG or HbA1c between groups. Conclusions: Early use of CSII post-T1D-diagnosis in a pediatric population is associated with a higher 1,5-AG than with MDI therapy implying reduced glycaemic variability. Disclosure E.S. Scott: None. A.S. Januszewski: None. G. Fulcher: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Research & Development, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Research & Development, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Research Support; Self; Novo Nordisk Inc. T. Jones: Research Support; Self; Dexcom, Inc., Medtronic MiniMed, Inc. Speaker's Bureau; Self; Eli Lilly and Company, Roche Diabetes Care. E.A. Davis: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.

Objective: Despite therapeutic advances, type 1 diabetes (T1D) is associated with a risk of development of micro- and macrovascular complications. Early treatment of complications is associated with a more favorable prognosis, hence biomarkers to enable early detection and to monitor treatments may be useful. Methods: Plasma (EDTA) samples were obtained from 30 adult (M/F = 20/10) individuals with T1D, age 42±16 years, T1D duration 24±11 years, HbA1c 7.5±1.2% and BMI 26.5±4.0 kg/m2 (15 with microvascular complications (retinopathy or nephropathy) - CX+, and 15 without complications - CX-) and compared with 15 nondiabetic controls (CON, matched age, gender, smoking and BMI). T1D CX+ and CX- individuals were matched for age, gender, diabetes duration, smoking, BMI, HbA1c and insulin therapy modality (CSII/MDI). In these discovery cohort samples, profiling of 754 miRs was done using a high throughput probe based quantitative PCR on nanofluidics Open Array platform . Results were analyzed using independent T test, Mann-Whitney test and classification trees. Statistical analysis was undertaken using R (ver. 3.5.1) and XLStat (ver. 2018.6). Results: Of 754 available miRs on the array, 186 miRs were detectable in plasma. Using an unbiased approach expression of 32 miRs differed significantly in CON vs. T1D and 16 miRs were differentially expressed between CX+ and CX- T1D subjects. Using a Random Forest wrapper algorithm 5 miRs were identified with importance for segregating CX+ vs. CX- status: miR-483-5p, miR-328, miR-1274B, miR-7 and miR-30a-5p. In logistic regression those 5 miRs provided a ROC curve with AUC=0.90 for the CX+ vs. CX- discrimination. Conclusion: In a discovery analysis of well- matched CX+ and CX- selected miRs provided good discrimination between T1D CX status. Validation studies in a larger cohort of cross-sectional and longitudinal samples are in progress. Disclosure A.S. Januszewski: None. E.S. Scott: None. M. Joglekar: None. L. Carroll: None. R. Farr: None. W. Wong: None. D.N. O’Neal: None. C. Karschimkus: None. G. Fulcher: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Research & Development, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Research & Development, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Research Support; Self; Novo Nordisk Inc. A. Hardikar: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. Funding Sydney Medical School Foundation; National Health and Medical Research Council of Australia

Background: The FIELD study, a 5-year randomized double-blind placebo-controlled trial of fenofibrate vs. placebo in 9,795 adults with type 2 diabetes (T2D), was designed to evaluate effects on coronary and cardiovascular (CV) events. In this analysis we explored associations between lipoprotein subfractions and on-study CV events and death. Methods: We performed ultracentrifugation using the vertical auto profile (VAP, Atherotech) on plasma at baseline and after 6 weeks of fenofibrate (active run-in) exposure. Analyses were performed using Cox proportional hazards and logistic regression analysis. Results were adjusted for gender, with log transformation as necessary. Results: Total CVD and CV death correlated negatively with HDL-C and its subfractions, as well as apoA1 and apoA2. In addition to LDL-C, small, dense LDL (LDL4-C), non-HDL-C, apo B, triglycerides, and apoC3 increased risk for total CVD. For CVD death, HDL-C and its subfractions were protective, while apo B, triglycerides, apo C3, and various VLDL-C species were associated with increased risk. Conclusions: Detailed lipoprotein analysis identifies multiple lipoprotein subclasses and apolipoproteins and their ratios associated with acute cardiovascular events and death. Serum levels of a number of these lipoprotein and apoprotein species were improved by fenofibrate therapy. Disclosure S.R. Jones: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.S. Januszewski: None. R.L. OConnell: None. L. Li: None. D. Sullivan: None. M. Taskinen: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Akcea Therapeutics, Chiesi USA, Inc. Research Support; Self; Amgen Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; Amgen Inc. R. Scott: None. G.F. Watts: None. P.J. Barter: Advisory Panel; Self; Merck & Co., Inc., Pfizer Inc. R. Simes: None. P.P. Toth: Consultant; Self; Amarin Corporation, Amgen Inc., AstraZeneca, Kowa Pharmaceutical Europe Co. Ltd., Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Amgen Inc., Merck & Co., Inc., Novo Nordisk Inc., Regeneron Pharmaceuticals, Sanofi US. A.C. Keech: None.

Introduction: Reviewing rCGM patterns may prompt lifestyle or therapeutic changes to achieve glycaemic targets but evidence for rCGM use in primary care management of T2D is limited. Methods: Two-arm RCT. Participants: Adults with T2D, HbA1c ≥0.5% above target, prescribed ≥2 non-insulin glycemia medications or insulin. Intervention: 1-hour diabetes education and (at 0/3/6/9/12 months): HbA1c assessment + wearing FreeStyle Libre Pro (Abbott) for up to 14 days prior to being discussed at a clinic visit. Physicians were trained in interpreting ambulatory glucose profiles. Control: 3-monthly ‘usual care’ clinic visits + r-CGM device worn (blinded, research data) at 0 and 12 months. Primary outcome: difference in mean HbA1c at 12 months. Secondary outcomes: mean differences in time in range (TIR: 4-10 mmol/L) and diabetes-specific distress (PAID) at 12 months, and HbA1c at 6 months. ITT analysis. Results: In 25 primary care practices, participants were: 299 adults with T2D, aged (mean(SD)) 60(10) years, HbA1c: 8.9(1.2)%, diabetes duration (median(IQR)) of 12(8,20) years. At 12 months, the between-group difference in mean HbA1c was 0.2% (p=0.112). The estimated mean percentage TIR was 8.4% higher in the intervention than the control arm (p=0.004). Diabetes-specific distress did not differ between arms (0.5; p=0.71). At 6 months, HbA1c was significantly lower in the intervention arm (0.5%; p Discussion: Use of 3-monthly rCGM in adults with T2D in primary care does not improve HbA1c at 12 months. We showed a statistically and clinically significant reduction in HbA1c at 6 months in the intervention group, as well as significant improvements in TIR at 12 months, with no change in diabetes distress. Our findings suggest the primary impact of r-CGM use on HbA1c in this setting is short term, and not associated with increase in the number of diabetes medications. Disclosure J. Furler: Research Support; Self; Abbott, Sanofi. D.N. O’Neal: None. J. Speight: Research Support; Self; AstraZeneca, Medtronic, Sanofi. Speaker’s Bureau; Self; Novo Nordisk A/S, Roche Diabetes Care. J.E. Manski-Nankervis: Research Support; Self; Australian National Health and Medical Research Council, Boehringer Ingelheim International GmbH, Diabetes Australia, Eli Lilly and Company. Speaker’s Bureau; Self; RACGP. S. Thuraisingam: None. E. Holmes-Truscott: Research Support; Self; Sanofi. Speaker’s Bureau; Self; Novo Nordisk Inc. K.R. De La Rue: None. L.E. Ginnivan: None. R.C. Doyle: None. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker’s Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited. M. Catchpool: None. K. Dalziel: None. J.I. Chiang: None. I. Blackberry: None. R. Audehm: Advisory Panel; Self; AstraZeneca, Novartis Pharmaceuticals Corporation. M. Kennedy: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. M.J. Clark: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.S. Januszewski: None. D. Liew: Advisory Panel; Self; AstraZeneca, Bayer AG. Research Support; Self; AbbVie Inc., AstraZeneca, Bristol-Myers Squibb Company, CSL Behring, Pfizer Inc. P.M. Clarke: None. J.D. Best: Consultant; Self; Abbott. Funding National Health and Medical Research Council of Australia (APP1104241); Sanofi Australia; Abbott Diabetes Care

Objective: Contrasting findings exist regarding the associations between circulating sex hormone-binding globulin (SHBG) and total testosterone (TT) with type 2 diabetes (T2D) and cardiovascular diseases (CVD) in men. We examined prospective associations of SHBG and TT with incident T2D and CVD, in a cohort of community-dwelling men. Methods: Participants were aged 35 years and over at enrolment (n=2563) and followed for an average of 4.95 years. This analysis included men without T2D (1597) or CVD (1492) at baseline, and with fasted morning serum SHBG (chemiluminescent immunoassay) and TT (LCMSMS) at both time points, and without meds affecting TT or SHBG. T2D was identified by either self-report, fasting glucose (≥7.0 mmol/L), HbA1c (≥ 6.5%) and/or prescriptions for diabetes medications. CVD was ascertained by self-report and/or hospital data linkage. Logistic binomial regressions were used to assess associations between SHBG and incident T2D & CVD, adjusting for self-reported psycho-social, demographic and health status and related behavioural factors; measured waist circumference, HBA1c and plasma glucose, triglycerides, high-sensitivity C-reactive protein. Sensitivity analyses assessed mediation effects of anxiety, sleep duration, shift work ≥3years, and obstructive sleep apnoea (OSA). Results: During an average follow-up of 4.95 years, 14.5% (n=232) and 6.7% (n=101) of men developed T2D and CVD, respectively. Baseline TT was independently associated with incident T2D (odds ratio (OR) =0.72, 95%CI= [0.57, 0.92], P=0.01). An inverse association of baseline SHBG levels with incident T2D (OR=0.77 [0.62, 0.95], P=0.02), was insignificant after adjustment for TT (OR=0.91 [0.71, 1.17], P=0.48 for SHBG. Baseline TT (OR=0.71 [0.52, 0.98], P=0.04) and SHBG (OR=1.54 [1.15, 2.06], P=0.003) were independently associated with incident CVD. A decrease in TT between time points was associated with incident T2D (OR=0.81 [0.68, 0.97], P=0.02) and CVD (OR=0.72 [0.56,0.92], P=0.01). There was no association between ΔSHBG and incident T2D and CVD. In the sensitivity analyses there was evidence for mediation effects of shift-work on the association of TT, but not SHBG with CVD (both baseline &change models), and of longer sleep duration, OSA and shift work on the association of TT with T2D (change TT model only). Conclusions Shift-work mediates associations of TT with CVD. All sleep parameters had mediation effects on the association of decreasing TT with T2D. Funding: NH&MRC Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Background Higher plasma fibroblast growth factor 21 (FGF21) levels predict incident cardiovascular events in type 2 diabetes patients. However, whether FGF21 levels predict cardiovascular events in statin-treated patients in the general population is unknown. We investigated whether FGF21 levels predict major cardiovascular event (MCVE) in the Treating to New Targets (TNT) trial participants. Methods After 8-week run-in on atorvastatin 10 mg/day, 10,001 patients with stable coronary disease in the TNT trial were randomized to 10 mg or 80 mg/day of atorvastatin for a median of 4.9 years. We analyzed data from 1996 patients with plasma FGF21 levels measured at randomization. Among them, 1835 patients had FGF21 measured one-year post-randomization. Results Higher ln-transformed FGF21 levels at randomization were associated with higher risk of incident MCVE (adjusted hazards ratio per SD increase = 1.18, P = 0.019). At 1-year post-randomization, FGF21 levels were lower in patients randomized to receive 80 mg versus 10 mg atorvastatin (186.9 versus 207.5 pg/mL respectively, P = 0.006). Higher ln-transformed FGF21 levels at 1-year post-randomization were also associated with higher subsequent risk of MCVEs (adjusted hazards ratio per SD increase = 1.24, P = 0.009). However, changes in FGF21 levels over 1-year were not related to subsequent MCVE risk. FGF21 levels had significant incremental value in net reclassification improvement in MCVE risk prediction. Conclusions Higher plasma FGF21 levels are associated with higher CVD risk in statin-treated high-risk patients. Higher dose atorvastatin is associated with a reduction in FGF21 levels. FGF21 provides incremental value in CVD risk prediction in statin-treated patients.