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2. High plasma FGF21 levels predicts major cardiovascular events in patients treated with atorvastatin (from the Treating to New Targets [TNT] Study)

Author

Ong, Kwok Leung, Hui, Nicholas, Januszewski, Andrzej S, Kaakoush, Nadeem O, Xu, Aimin, Fayyad, Rana, DeMicco, David A, Jenkins, Alicia J, Keech, Anthony C, Waters, David D, Barter, Philip J, and Rye, Kerry-Anne

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Heart Disease, Clinical Trials and Supportive Activities, Cardiovascular, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Aged, Anticholesteremic Agents, Atorvastatin, Biomarkers, Cardiovascular Diseases, Coronary Artery Disease, Female, Fibroblast Growth Factors, Humans, Male, Middle Aged, Predictive Value of Tests, Endocrinology & Metabolism, Clinical sciences
Abstract

BackgroundHigher 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.MethodsAfter 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.ResultsHigher 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.ConclusionsHigher 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.

Published
2019

3. Machine learning workflows identify a microRNA signature of insulin transcription in human tissues

Author

Wong, Wilson K.M., Joglekar, Mugdha V., Saini, Vijit, Jiang, Guozhi, Dong, Charlotte X., Chaitarvornkit, Alissa, Maciag, Grzegorz J., Gerace, Dario, Farr, Ryan J., Satoor, Sarang N., Sahu, Subhshri, Sharangdhar, Tejaswini, Ahmed, Asma S., Chew, Yi Vee, Liuwantara, David, Heng, Benjamin, Lim, Chai K., Hunter, Julie, Januszewski, Andrzej S., Sørensen, Anja E., Akil, Ammira S.A., Gamble, Jennifer R., Loudovaris, Thomas, Kay, Thomas W., Thomas, Helen E., O'Connell, Philip J., Guillemin, Gilles J., Martin, David, Simpson, Ann M., Hawthorne, Wayne J., Dalgaard, Louise T., Ma, Ronald C.W., and Hardikar, Anandwardhan A.

Published
2021
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4. Haptoglobin phenotype and levels in type 2 diabetes and effects of fenofibrate.

Author

Januszewski, Andrzej S., Young, Hayden K., Ong, Kwok‐Leung, Li, Liping, O’Connell, Rachel L., Lyons, Timothy J., Kelly, Clare, Zaharieva, Dessi P., Sullivan, David R., Scott, Russell S., Keech, Anthony C., and Jenkins, Alicia J.

Subjects
*TYPE 2 diabetes, *FENOFIBRATE, *PHENOTYPES, *DIABETES, *ADULTS
Abstract

ABSTRACT Aims/Hypothesis Materials and Methods Results Conclusions In diabetes haptoglobin (Hp) 2 vs Hp 1 allelic product is associated with cardiac and renal complications. Few studies report both Hp phenotype and Hp levels. In a Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial substudy we evaluated the Hp phenotype, Hp levels, and fenofibrate effects.In 480 adults with type 2 diabetes (T2D) the Hp phenotype was assessed and the Hp level quantified (both using ELISAs assays) in plasma from baseline, after 6 weeks of fenofibrate, and (in n = 200) at 2 years post‐randomization to fenofibrate or placebo.The Hp phenotypes 1‐1, 2‐1, and 2‐2 frequencies were 15%, 49%, and 36%, respectively. Baseline Hp levels differed by phenotype (P < 0.0001) and decreased (median 21%) after 6 weeks fenofibrate in all phenotypes (adjusted mean (95% CI): −0.27 (−0.32, −0.23) mg/mL in Hp 1‐1, −0.29 (−0.31, −0.27) mg/mL in Hp 2‐1 and −0.05 (−0.07, −0.02) mg/mL in Hp 2‐2 (P = 0.005 and P = 0.055 vs Hp 1‐1 and Hp 2‐1, respectively)). At 2 years post‐randomization the Hp levels in the placebo group had returned to baseline, whilst the fenofibrate‐group levels remained similar to the 6 week levels.In type 2 diabetes, Hp levels differ by Hp phenotype and are decreased by fenofibrate in all phenotypes, but the effect is diminished in Hp 2‐2. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Cardiometabolic risk factors, peripheral arterial tonometry and metformin in adults with type 1 diabetes participating in the REducing with MetfOrmin Vascular Adverse Lesions trial

Author

Chen, David, primary, Jenkins, Alicia J, additional, Greenlaw, Nicola, additional, Dudman, Katie, additional, Fernandes, Tamsin, additional, Carty, David M, additional, Hughes, Alun D, additional, Januszewski, Andrzej S, additional, Stehouwer, Coen DA, additional, and Petrie, John R, additional

Published
2023
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12. Optimal Frequency of Retinopathy Screening in Adolescents With Type 1 Diabetes: Markov Modeling Approach Based on 30 Years of Data

Author

Januszewski, Andrzej S., primary, Velayutham, Vallimayil, additional, Benitez-Aguirre, Paul Z., additional, Craig, Maria E., additional, Cusumano, Janine, additional, Pryke, Alison, additional, Hing, Stephen, additional, Liew, Gerald, additional, Cho, Yoon Hi, additional, Chew, Emily Y., additional, Jenkins, Alicia J., additional, and Donaghue, Kim C., additional

Published
2022
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17. Telomeres do not always shorten over time in individuals with type 1 diabetes

Author

Behalf FinnDiane Study Grp, Syreeni, Anna, Carroll, Luke M., Mutter, Stefan, Januszewski, Andrzej S., Forsblom, Carol, Lehto, Markku, Groop, Per-Henrik, Jenkins, Alicia J., HUS Abdominal Center, University of Helsinki, Clinicum, CAMM - Research Program for Clinical and Molecular Metabolism, Nefrologian yksikkö, Department of Medicine, and Per Henrik Groop / Principal Investigator

Subjects
RISK, Male, NEPHROPATHY, Endocrinology, Diabetes and Metabolism, Cholesterol, HDL, Telomere Homeostasis, ASSOCIATION, General Medicine, Telomere, DISEASE, Type 1 diabetes, Telomere length change, Kidney function, Diabetes Mellitus, Type 1, Endocrinology, 3121 General medicine, internal medicine and other clinical medicine, CELLS, LENGTH, Leukocytes, Internal Medicine, HEART, ATTRITION, STATINS, Humans, Obesity
Abstract

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.

Published
2022

18. The relationship of neutrophil elastase and proteinase 3 with risk factors, and chronic complications in type 2 diabetes: A Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) sub-study

Author

Ong, Kwok-Leung, primary, Wu, Liang, additional, Januszewski, Andrzej S, additional, O’Connell, Rachel, additional, Xu, Aimin, additional, Scott, Russell S, additional, Sullivan, David R, additional, Rye, Kerry-Anne, additional, Li, Huating, additional, Ma, Ronald CW, additional, Li, Liping, additional, Gebski, Val, additional, Jenkins, Alicia J, additional, Jia, Weiping, additional, and Keech, Anthony C, additional

Published
2021
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21. sj-pdf-1-dvr-10.1177_14791641211032547 – Supplemental material for The relationship of neutrophil elastase and proteinase 3 with risk factors, and chronic complications in type 2 diabetes: A Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) sub-study

Author

Ong, Kwok-Leung, Wu, Liang, Januszewski, Andrzej S, O’Connell, Rachel, Xu, Aimin, Scott, Russell S, Sullivan, David R, Rye, Kerry-Anne, Li, Huating, Ma, Ronald CW, Li, Liping, Gebski, Val, Jenkins, Alicia J, Jia, Weiping, and Keech, Anthony C

Subjects
FOS: Clinical medicine, 111199 Nutrition and Dietetics not elsewhere classified, Cardiology, 110323 Surgery, FOS: Health sciences, 110306 Endocrinology
Abstract

Supplemental material, sj-pdf-1-dvr-10.1177_14791641211032547 for The relationship of neutrophil elastase and proteinase 3 with risk factors, and chronic complications in type 2 diabetes: A Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) sub-study by Kwok-Leung Ong, Liang Wu, Andrzej S Januszewski, Rachel O’Connell, Aimin Xu, Russell S Scott, David R Sullivan, Kerry-Anne Rye, Huating Li, Ronald CW Ma, Liping Li, Val Gebski, Alicia J Jenkins, Weiping Jia and Anthony C Keech in Diabetes & Vascular Disease Research

Published
2021
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26. Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome

Author

Sørensen, Anja E., Udesen, Pernille B., Maciag, Grzegorz, Geiger, Julian, Saliani, Negar, Januszewski, Andrzej S., Jiang, Guozhi, Ma, Ronald C., Hardikar, Anandwardhan A., Wissing, Marie Louise M., Englund, Anne Lis M., Dalgaard, Louise T., Sørensen, Anja E., Udesen, Pernille B., Maciag, Grzegorz, Geiger, Julian, Saliani, Negar, Januszewski, Andrzej S., Jiang, Guozhi, Ma, Ronald C., Hardikar, Anandwardhan A., Wissing, Marie Louise M., Englund, Anne Lis M., and Dalgaard, Louise T.

Abstract

Polycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome (MetS). Accordingly, we measured serum levels of miRNAs as well as biochemical markers related to MetS in a case-control study of 42 PCOS patients and 20 Controls. Patients were diagnosed based on the Rotterdam consensus criteria and stratified based on serum free testosterone levels (≥0.034 nmol/l) into either a normoandrogenic (n = 23) or hyperandrogenic (n = 19) PCOS group. Overall, hyperandrogenic PCOS women were more insulin resistant compared to normoandrogenic PCOS women and had a higher prevalence of MetS. A total of 750 different miRNAs were analyzed using TaqMan Low-Density Arrays. Altered levels of seven miRNAs (miR-485-3p, -1290, -21-3p, -139-3p, -361-5p, -572, and -143-3p) were observed in PCOS patients when compared with healthy Controls. Stratification of PCOS women revealed that 20 miRNAs were differentially expressed between the three groups. Elevated serum free testosterone levels, adjusted for age and BMI, were significantly associated with five miRNAs (miR-1290, -20a-5p, -139-3p, -433-3p, and -361-5p). Using binary logistic regression and receiver operating characteristic curves (ROC), a combination panel of three miRNAs (miR-361-5p, -1225-3p, and -34-3p) could correctly identify all of the MetS cases within the PCOS group. This study is the first to report comprehensive miRNA profiling in different subgroups of PCOS women with respect to MetS and suggests that circulating miRNAs might be useful as diagnostic biomarkers of MetS for a different subset of PCOS.

Published
2019

28. Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome

Author

Sørensen, Anja E., primary, Udesen, Pernille B., additional, Maciag, Grzegorz, additional, Geiger, Julian, additional, Saliani, Negar, additional, Januszewski, Andrzej S., additional, Jiang, Guozhi, additional, Ma, Ronald C., additional, Hardikar, Anandwardhan A., additional, Wissing, Marie Louise M., additional, Englund, Anne Lis M., additional, and Dalgaard, Louise T., additional

Published
2019
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30. 41-LB: Lipoprotein Subfractions Are Associated with Diabetic Microvascular Disease among 9,795 Patients in the FIELD Trial

Author

TOTH, PETER P., primary, KEECH, ANTHONY C., additional, JANUSZEWSKI, ANDRZEJ S., additional, OCONNELL, RACHEL L., additional, LI, LIPING, additional, SULLIVAN, DAVID, additional, TASKINEN, MARJA-RIITTA, additional, DRURY, PAUL L., additional, WATTS, GERALD FRANCIS, additional, BEST, JAMES D., additional, ANSQUER, JEAN CLAUDE, additional, JONES, STEVEN R., additional, and JENKINS, ALICIA J., additional

Published
2019
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32. 38-LB: Discovery Analysis of MicroRNAs (miRs) Associated with Microvascular Complications in Adults with Type 1 Diabetes

Author

JANUSZEWSKI, ANDRZEJ S., primary, SCOTT, EMMA S., additional, JOGLEKAR, MUGDHA, additional, CARROLL, LUKE, additional, FARR, RYAN, additional, WONG, WILSON, additional, O’NEAL, DAVID N., additional, KARSCHIMKUS, CONNIE, additional, FULCHER, GREG, additional, HARDIKAR, ANAND, additional, and JENKINS, ALICIA J., additional

Published
2019
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33. 22-LB: Baseline and Short-Term Change in Plasma Uric Acid on Fenofibrate Predict Cardiovascular Risk: A Post Hoc Analysis of FIELD

Author

YIMING CAO, JACOB, primary, WALDMAN, BORIS, additional, OCONNELL, RACHEL L., additional, SULLIVAN, DAVID, additional, GEBSKI, VAL, additional, JANUSZEWSKI, ANDRZEJ S., additional, MARSCHNER, IAN, additional, SCOTT, RUSSELL, additional, TASKINEN, MARJA-RIITTA, additional, SIMES, R. JOHN, additional, MCGILL, NEIL, additional, JENKINS, ALICIA J., additional, and KEECH, ANTHONY C., additional

Published
2019
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35. Suboptimal behaviour and knowledge regarding overnight glycaemia in adults with type 1 diabetes is common

Author

Larsson, Christina R., Januszewski, Andrzej S., McGrath, Rachel T., Ludvigsson, Johnny, Keech, Anthony C., MacIsaac, Richard J., Ward, Glenn M., ONeal, David N., Fulcher, Gregory R., Jenkins, Alicia J., Larsson, Christina R., Januszewski, Andrzej S., McGrath, Rachel T., Ludvigsson, Johnny, Keech, Anthony C., MacIsaac, Richard J., Ward, Glenn M., ONeal, David N., Fulcher, Gregory R., and Jenkins, Alicia J.

Abstract

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., Funding Agencies|CSN (Centrala studiestodsnamnden); NHMRC; University of Sydney, Sydney Medical School Foundation

Published
2018
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36. Cross-sectional and longitudinal determinants of serum sex hormone binding globulin (SHBG) in a cohort of community-dwelling men

Author

Gyawali, Prabin, primary, Martin, Sean A., additional, Heilbronn, Leonie K., additional, Vincent, Andrew D., additional, Jenkins, Alicia J., additional, Januszewski, Andrzej S., additional, Taylor, Anne W., additional, Adams, Robert J. T., additional, O’Loughlin, Peter D., additional, and Wittert, Gary A., additional

Published
2018
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37. Effect of a high-egg diet on cardiometabolic risk factors in people with type 2 diabetes: the Diabetes and Egg (DIABEGG) Study—randomized weight-loss and follow-up phase

Author

Fuller, Nicholas R, primary, Sainsbury, Amanda, additional, Caterson, Ian D, additional, Denyer, Gareth, additional, Fong, Mackenzie, additional, Gerofi, James, additional, Leung, Chloris, additional, Lau, Namson S, additional, Williams, Kathryn H, additional, Januszewski, Andrzej S, additional, Jenkins, Alicia J, additional, and Markovic, Tania P, additional

Published
2018
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38. Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Author

Williams, Kathryn H, Sullivan, David R, Nicholson, Geoffrey C, George, Jacob, Jenkins, Alicia J, Januszewski, Andrzej S, Gebski, Val J, Manning, Patrick, Tan, Yong Mong, Donoghoe, Mark W, Ehnholm, Christian, Young, Simon, O'Brien, Richard, Buizen, Luke, Twigg, Stephen M, and Keech, Anthony C

Subjects
γ-glutamyl transferase, diabetes, alanine aminotransferase, digestive system, mortality, digestive system diseases, non-alcoholic fatty liver disease (NAFLD)
Abstract

Aims Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms. Methods Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analysed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5 years. Results Over 5 years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p70 U/L, compared with GGT ≤70 U/L, had HR 1.82 (1.48−2.24), p70 U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP. Conclusions As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship 4 for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes.

Published
2016

39. Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation

Author

Hardikar, Anandwardhan A., Satoor, Sarang N., Karandikar, Mahesh S., Joglekar, Mugdha V., Puranik, Amrutesh S., Wong, Wilson, Kumar, Sandeep, Limaye, Amita, Bhat, Dattatray S., Januszewski, Andrzej S., Umrani, Malati R., Ranjan, Amaresh K., Apte, Kishori, Yajnik, Pranav, Bhonde, Ramesh R., Galande, Sanjeev, Keech, Anthony C., Jenkins, Alicia J., and Yajnik, Chittaranjan S.

Published
2015
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40. Baseline Circulating FGF21 Concentrations and Increase after Fenofibrate Treatment Predict More Rapid Glycemic Progression in Type 2 Diabetes: Results from the FIELD Study

Author

Ong, Kwok-Leung, primary, O'Connell, Rachel, primary, Januszewski, Andrzej S, primary, Jenkins, Alicia J, primary, Xu, Aimin, primary, Sullivan, David R, primary, Barter, Philip J, primary, Scott, Russell S, primary, Taskinen, Marja-Riitta, primary, Waldman, Boris, primary, Colman, Peter G, primary, Best, James D, primary, Simes, John R, primary, Rye, Kerry-Anne, primary, and Keech, Anthony C, primary

Published
2017
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41. The relationship of fibroblast growth factor 21 with cardiovascular outcome events in the Fenofibrate Intervention and Event Lowering in Diabetes study

Author

Ong, Kwok-Leung, Januszewski, Andrzej S, O'Connell, Rachel, Jenkins, Alicia J, Xu, Aimin, Sullivan, David R, Barter, Philip J, Hung, Wei-Ting, Scott, Russell S, Taskinen, Marja-Riitta, Keech, Anthony C, and Rye, Kerry-Anne

Subjects
cardiovascular disease, fibroblast growth factor 21, fenofibrate, type 2 diabetes
Abstract

Aims/hypothesis Circulating fibroblast growth factor 21 (FGF21) levels are often elevated in obesity, dyslipidaemia, insulin resistance and type 2 diabetes. This study investigated the relationship of plasma FGF21 levels with cardiovascular events in patients with type 2 diabetes. Methods Plasma FGF21 levels were measured at baseline in 9,697 study participants with type 2 diabetes from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study by enzyme-linked immunosorbent assay. We assessed the association of FGF21 levels with incidence of different cardiovascular outcomes over 5-years. The primary outcome was total cardiovascular disease (CVD) events, and the secondary outcomes were the four individual components: coronary heart disease (CHD) events, total stroke, CVD mortality, coronary and carotid revascularization. Tertiary outcome was hospitalisation for angina pectoris. Results Higher baseline FGF21 levels were associated with higher risks of all cardiovascular outcome events after adjusting for the study treatment allocation (all p

Published
2014

43. A comparative analysis of high-throughput platforms for validation of a circulating microRNA signature in diabetic retinopathy

Author

Farr, Ryan J., primary, Januszewski, Andrzej S., additional, Joglekar, Mugdha V., additional, Liang, Helena, additional, McAulley, Annie K., additional, Hewitt, Alex W., additional, Thomas, Helen E., additional, Loudovaris, Tom, additional, Kay, Thomas W. H., additional, Jenkins, Alicia, additional, and Hardikar, Anandwardhan A., additional

Published
2015
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44. Biomarkers in Diabetic Retinopathy

Author

Jenkins, Alicia J., primary, Joglekar, Mugdha V., additional, Hardikar, Anandwardhan A., additional, Keech, Anthony C., additional, O'Neal, David N., additional, and Januszewski, Andrzej S., additional

Published
2015
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45. Baseline Circulating FGF21 Concentrations and Increase after Fenofibrate Treatment Predict More Rapid Glycemic Progression in Type 2 Diabetes: Results from the FIELD Study.

Author

Kwok-Leung Ong, O’Connell, Rachel, Januszewski, Andrzej S., Jenkins, Alicia J., Aimin Xu, Sullivan, David R., Barter, Philip J., Scott, Russell S., Taskinen, Marja-Riitta, Waldman, Boris, Colman, Peter G., Best, James D., Simes, John R., Rye, Kerry-Anne, and Keech, Anthony C.

Published
2017
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46. The relationship of fibroblast growth factor 21 with cardiovascular outcome events in the Fenofibrate Intervention and Event Lowering in Diabetes study

Author

Ong, Kwok-Leung, primary, Januszewski, Andrzej S., additional, O’Connell, Rachel, additional, Jenkins, Alicia J., additional, Xu, Aimin, additional, Sullivan, David R., additional, Barter, Philip J., additional, Hung, Wei-Ting, additional, Scott, Russell S., additional, Taskinen, Marja-Riitta, additional, Keech, Anthony C., additional, and Rye, Kerry-Anne, additional

Published
2014
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48. Longitudinal analysis of low-molecular weight fluorophores in type 1 diabetes mellitus

Author

Januszewski, Andrzej S, Thomas, Merlin C, Karschimkus, Connie S, Chung, Jasmine S, Rowley, Kevin G, Nelson, Craig L, O’Neal, David N, Dragicevic, George, Harper, Colin A, Best, James D, Jenkins, Alicia J, Januszewski, Andrzej S, Thomas, Merlin C, Karschimkus, Connie S, Chung, Jasmine S, Rowley, Kevin G, Nelson, Craig L, O’Neal, David N, Dragicevic, George, Harper, Colin A, Best, James D, and Jenkins, Alicia J

Abstract

Objectives : Circulating low molecular weight (<10 kDa) fluorophores (LMW-F) measured by non-specific fluorescence spectroscopy may detect small advanced glycation end-products (AGEs) not recognized by other assays. This longitudinal study assessed correlates of LMW-F and predictive power of LMW-F levels for vascular health in Type 1 diabetes (T1DM) patients. Methods : Fasting patients with T1DM (n=37) were studied twice at intervals of 12-60 months (mean±SD, 33±15 months). LMW-F levels were also measured once in 112 healthy control subjects. Results : Relative to controls, LMW-F levels were higher in diabetic subjects at initial and final time points (mean±SD), 5.4±1.9 AU/ml and 4.5±1.8 AU/ml respectively vs. 3.8±2.1 AU/ml p=0.0001 and p=0.06). Baseline LMW-F levels predicted subsequent hs-CRP and oxLDL/LDL values. LMW-F levels decreased significantly over time in diabetes (5.4±1.9 vs. 4.5±1.8 AU/ml p=0.02). Rises in LMW-F levels in individual diabetic subjects correlated significantly with worsening renal function (BUN), glycemia (HbA1c) and with vascular dysfunction (systemic vascular resistance). Conclusions : LMW-F levels predict levels of inflammation and oxidation in T1DM. Changes in LMW-F levels in T1DM reflect variations in glycemia and renal function. Biochemical characterization of LMW-F would facilitate understanding of the potential utility of LMW-F as a therapeutic target.

Published
2008

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