Publications by authors named "Harald Sourij"

94 Publications

EndoBarrier™ Implantation Rapidly Improves Insulin Sensitivity in Obese Individuals with Type 2 Diabetes Mellitus.

Biomolecules 2021 Apr 14;11(4). Epub 2021 Apr 14.

Division of Endocrinology and Diabetology, Medical University of Graz, 8010 Graz, Austria.

The EndoBarrier™ medical device is a duodenal-jejunal bypass liner designed to mimic the effects of gastric bypass surgery to induce weight loss and glycaemic improvement. In this study, 10 participants with type 2 diabetes mellitus (T2DM), a mean body mass index (BMI) of 43.3 ± 5.0 (kg/m) and a mean glycated haemoglobin A1c (HbA1c) of 60.6 ± 8.6 mmol/mol were examined at baseline (before implantation of EndoBarrier™), 4 weeks after implantation, at 36 weeks (right before explantation) and 24 weeks after the removal of the device to explore the short and long-term effects on glucose metabolism. Besides a significant reduction in body weight and fat mass, EndoBarrier™ treatment significantly improved insulin sensitivity during Botnia clamp investigations after four weeks of implantation. The beneficial effects decreased over time but remained significant 24 weeks after removal of the device.
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http://dx.doi.org/10.3390/biom11040574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070956PMC
April 2021

Can sodium glucose cotransporter 2 (SGLT-2) inhibitors be beneficial in patients with acute myocardial infarction?

Kardiol Pol 2021 Apr 20. Epub 2021 Apr 20.

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin, dapagliflozin, and canagliflozin have shown impressive beneficial effects in patients with type-2 diabetes mellitus in mandatory cardiovascular outcome trials. Retrospective data analysis revealed signals that pointed towards positive effects independent of the antidiabetic effects. This could be confirmed for empagliflozin and dapagliflozin in circumstances of chronic heart failure with reduced ejection fraction alone, where rates for hospitalization for heart failure and cumulative major adverse cardiovascular events were reduced in a similar extend in patients with and without diabetes mellitus in corresponding outcome trials. Cardiac remodelling following myocardial infarction leads to heart failure with reduced ejection fraction in many patients and aggravates morbidity and mortality. Clinical data of SGLT2i treatment after acute myocardial infarction is sparse. This review focuses on available experimental data on the effects of SGLT2i used before, during, and after myocardial infarction as well as already published and currently ongoing clinical trials.
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http://dx.doi.org/10.33963/KP.15969DOI Listing
April 2021

Admission levels of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Associate with Development of Severe Complications in Hospitalised COVID-19 Patients: A Prospective Cohort Study.

Int J Infect Dis 2021 Apr 13. Epub 2021 Apr 13.

Zayed Center for Health Sciences, United Arab Emirates University, United Arab Emirates; Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Austria.

Objective: To examine the association between plasma levels of the soluble urokinase plasminogen activator receptor (suPAR) and the incidence of severe complications of COVID-19.

Methods: 403 RT-PCR-confirmed COVID-19 patients were recruited and prospectively followed-up at a major hospital in the United Arab Emirates. The primary endpoint was time from admission until the development of a composite outcome, including acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, or death from any cause. Patients discharged alive were considered as competing events to the primary outcome. Competing risk regression was used to quantify the association between suPAR and the incidence of the primary outcome.

Results: 6.2% of patients experienced ARDS or ICU admission, but none died. Taking into account competing risk, the incidence of the primary outcome was 11.5% (95% confidence interval [CI], 6.7-16.3) in patients with suPAR levels >3.91 ng/mL compared to 2.9% (95% CI, 0.4-5.5) in those with suPAR ≤3.91 ng/mL. Also, an increase by 1 ng/mL in baseline suPAR resulted in 58% rise in the hazard of developing the primary outcome (hazard ratio 1.6, 95% CI, 1.2-2.1, p =  0.003).

Conclusion: suPAR has an excellent prognostic utility in predicting severe complications in hospitalised COVID-19 patients.
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http://dx.doi.org/10.1016/j.ijid.2021.04.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056823PMC
April 2021

Impact of comorbidities on mortality in hospitalized influenza patients with diabetes - Analysis of the Austrian Health Insurance.

Diabetes Res Clin Pract 2021 Apr 17;174:108758. Epub 2021 Mar 17.

Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. Electronic address:

Aims: To assess the impact of characteristics and comorbidities on the hospitalization rate and 30- and 90-days all-cause mortality after hospitalization for influenza-related illness (IRI) in individuals with diabetes.

Methods: Data of 507,184 individuals with diabetes enrolled in the national Austrian Health Insurance database during 2013-2017 were analyzed. Hospitalization for IRI was defined as per International Classification of Disease 10 codes (J09, J10, J11). All-cause mortality was calculated for 30- and 90-days post-hospitalization.

Results: Of the total diabetes population, 1994 (0.4%) were hospitalized for IRI during 2013-2017. The rate of comorbidities was higher in individiuals who were hospitalized due to IRI as compared with the general diabetes population. Overall 30-days cumulative mortality following hospitalization for IRI was 7.9% and 90-days mortality was 10.3%. The risk (adjusted Hazard Ratio, 95% Confidence Interval) of IRI related 90-days mortality increased with age (50-59: 3.00, 0.65-13.94; 60-69: 4.16, 0.99-17.55; 70-79: 4.79, 1.16-19.76; 80+: 7.15, 1.74-29.46), heart failure (1.97, 1.31-2.98), renal disease (1.50, 1.05-2.14), and Charlson comorbidity index (1.14, 1.08-1.19).

Conclusions: Older age, heart failure, renal disease, and Charlson comorbidity index were significant predictors of mortality following hospitalization for IRI in individuals with diabetes. These findings could help in improving the clinical management and performance of surveillance and health systems concerning IRI in Austria.
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http://dx.doi.org/10.1016/j.diabres.2021.108758DOI Listing
April 2021

MicroRNAs and long non-coding RNAs in the pathophysiological processes of diabetic cardiomyopathy: emerging biomarkers and potential therapeutics.

Cardiovasc Diabetol 2021 Feb 27;20(1):55. Epub 2021 Feb 27.

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CEPT, Medical University of Warsaw, Banacha 1B Str., 02-097, Warsaw, Poland.

The epidemic of diabetes mellitus (DM) necessitates the development of novel therapeutic and preventative strategies to attenuate complications of this debilitating disease. Diabetic cardiomyopathy (DCM) is a frequent disorder affecting individuals diagnosed with DM characterized by left ventricular hypertrophy, diastolic and systolic dysfunction and myocardial fibrosis in the absence of other heart diseases. Progression of DCM is associated with impaired cardiac insulin metabolic signaling, increased oxidative stress, impaired mitochondrial and cardiomyocyte calcium metabolism, and inflammation. Various non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), as well as their target genes are implicated in the complex pathophysiology of DCM. It has been demonstrated that miRNAs and lncRNAs play an important role in maintaining homeostasis through regulation of multiple genes, thus they attract substantial scientific interest as biomarkers for diagnosis, prognosis and as a potential therapeutic strategy in DM complications. This article will review the different miRNAs and lncRNA studied in the context of DM, including type 1 and type 2 diabetes and the contribution of pathophysiological mechanisms including inflammatory response, oxidative stress, apoptosis, hypertrophy and fibrosis to the development of DCM .
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http://dx.doi.org/10.1186/s12933-021-01245-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916283PMC
February 2021

Performance of the Intermittently Scanned Continuous Glucose Monitoring (isCGM) System during a High Oral Glucose Challenge in Adults with Type 1 Diabetes-A Prospective Secondary Outcome Analysis.

Biosensors (Basel) 2021 Jan 15;11(1). Epub 2021 Jan 15.

Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.

To assess intermittently scanned continuous glucose monitoring (isCGM) performance for different rates of change in plasma glucose (RCPG) during glycemic challenges in type 1 diabetes (T1D). Nineteen people with T1D (7 females; age 35 ± 11 years; HbA 7.3 ± 0.6% (56 ± 7 mmol/mol)) performing two glycemic challenges (OGTT) were included. During OGTTs, plasma glucose was compared against sensor glucose for timepoints 0 min (pre-OGTT), +15 min, +30 min, +60 min, +120 min, +180 min, and +240 min by means of median absolute (relative) difference (MARD and MAD) and Clarke Error Grid (CEG), then was stratified for RCPG and glycemic ranges. Overall, MARD was 8.3% (4.0-14.8) during hypoglycemia level 1 18.8% (15.8-22.0), euglycemia 9.5% (4.3-15.1), hyperglycemia level 1 9.4% (4.0-17.2), and hyperglycemia level 2 7.1% (3.3-11.9). The MARD was associated with the RCPG ( < 0.0001), detailing significant differences in comparison of low, moderate, high, and very high RCPG ( = 0.014). Overall, CEG resulted in 88% (212 values) of comparison points in zone A, 12% (29 values) in zone B, and 0.4% (1 value) in zone D. The isCGM system was accurate during OGTTs. Its performance was dependent on the RCPG and showed an overestimation of the actual reference glucose during hypoglycemia.
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http://dx.doi.org/10.3390/bios11010022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830732PMC
January 2021

Rapid glucose rise reduces heart rate variability in adults with type 1 diabetes: A prospective secondary outcome analysis.

Diabetes Obes Metab 2020 Dec 7. Epub 2020 Dec 7.

Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

To investigate differences in heart rate variability (HRV) during oral glucose tolerance tests (OGTTs) in response to the rate of change in glucose and to different glycaemic ranges in individuals with type 1 diabetes. This was a single-centre, prospective, secondary outcome analysis in 17 individuals with type 1 diabetes (glycated haemoglobin 53 ± 6.3 mmol/L), who underwent two OGTTs (after 12 and 36 hours of fasting) investigating differences in HRV in response to rapid glucose increases/decreases and different glycaemic ranges during OGTT. Based on the rate of change in glucose level, the variables heart rate (P < 0.001), square root of the mean standard difference of successive R-R intervals (P = 0.002), percentage of pairs of R-R intervals with >50 ms difference (P < 0.001) and corrected QT interval (P = 0.04) were significantly altered, with HRV particularly reduced during episodes of rapid glucose rises. Glycaemic ranges during OGTT had no impact on HRV (P < 0.05). Individuals with type 1 diabetes showed no changes in HRV in response to different glycaemic ranges. HRV was dependent on the rate of change in glucose, especially rapid increases in glucose level.
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http://dx.doi.org/10.1111/dom.14287DOI Listing
December 2020

COVID-19 fatality prediction in people with diabetes and prediabetes using a simple score upon hospital admission.

Diabetes Obes Metab 2021 02 4;23(2):589-598. Epub 2020 Dec 4.

Department for Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria.

Aim: To assess predictors of in-hospital mortality in people with prediabetes and diabetes hospitalized for COVID-19 infection and to develop a risk score for identifying those at the greatest risk of a fatal outcome.

Materials And Methods: A combined prospective and retrospective, multicentre, cohort study was conducted at 10 sites in Austria in 247 people with diabetes or newly diagnosed prediabetes who were hospitalized with COVID-19. The primary outcome was in-hospital mortality and the predictor variables upon admission included clinical data, co-morbidities of diabetes or laboratory data. Logistic regression analyses were performed to identify significant predictors and to develop a risk score for in-hospital mortality.

Results: The mean age of people hospitalized (n = 238) for COVID-19 was 71.1 ± 12.9 years, 63.6% were males, 75.6% had type 2 diabetes, 4.6% had type 1 diabetes and 19.8% had prediabetes. The mean duration of hospital stay was 18 ± 16 days, 23.9% required ventilation therapy and 24.4% died in the hospital. The mortality rate in people with diabetes was numerically higher (26.7%) compared with those with prediabetes (14.9%) but without statistical significance (P = .128). A score including age, arterial occlusive disease, C-reactive protein, estimated glomerular filtration rate and aspartate aminotransferase levels at admission predicted in-hospital mortality with a C-statistic of 0.889 (95% CI: 0.837-0.941) and calibration of 1.000 (P = .909).

Conclusions: The in-hospital mortality for COVID-19 was high in people with diabetes but not significantly different to the risk in people with prediabetes. A risk score using five routinely available patient variables showed excellent predictive performance for assessing in-hospital mortality.
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http://dx.doi.org/10.1111/dom.14256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753560PMC
February 2021

Arylesterase Activity of HDL Associated Paraoxonase as a Potential Prognostic Marker in Patients With Sepsis and Septic Shock-A Prospective Pilot Study.

Front Med (Lausanne) 2020 22;7:579677. Epub 2020 Oct 22.

Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

High-density lipoprotein (HDL) plays an essential role in the immune system and shows effective antioxidative properties. We investigated correlations of lipid parameters with the sequential organ failure assessment (SOFA) score and the prognostic association with mortality in sepsis patients admitted to intensive care unit (ICU). We prospectively recruited consecutive adult patients with sepsis and septic shock, according to sepsis-3 criteria as well as non-sepsis ICU controls. Fifty-three patients with sepsis (49% with septic shock) and 25 ICU controls without sepsis were enrolled. Dyslipidemia (HDL-C < 40 mg/l) was more common in sepsis compared to non-sepsis patients (85 vs. 52%, = 0.002). Septic patients compared to controls had reduced HDL-C (14 vs. 39 mg/l, < 0.0001), lower arylesterase activity of the antioxidative paraoxonase of HDL (AEA) (67 vs. 111 mM/min/ml serum, < 0.0001), and a non-significant trend toward reduced cholesterol efflux capacity (9 vs. 10%, = 0.091). We observed a strong association between higher AEA and lower risk of 28-day [per 10 mM/min/ml serum increase in AEA: odds ratio (OR) = 0.76; 95% CI, 0.61-0.94; = 0.01) and ICU mortality (per 10 mM/min/ml serum increase in AEA: OR = 0.71, 95% CI, 0.56-0.90, = 0.004) in the sepsis cohort in univariable logistic regression analysis. AEA was confirmed as an independent predictor of 28-day and ICU mortality in multivariable analyses. AEA discriminated well-regarding 28-day/ICU mortality in area under the receiver operating characteristic curve (AUROC) analyses. In survival analysis, 28-day mortality estimates were 40 and 69% with AEA ≥/< the 25th percentile of AEA's distribution, respectively (log-rank = 0.0035). Both compositional and functional HDL parameters are profoundly altered during sepsis. In particular, the functionality parameter AEA shows promising prognostic potential in sepsis patients.
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http://dx.doi.org/10.3389/fmed.2020.579677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642222PMC
October 2020

Differences in Physiological Responses to Cardiopulmonary Exercise Testing in Adults With and Without Type 1 Diabetes: A Pooled Analysis.

Diabetes Care 2021 Jan 12;44(1):240-247. Epub 2020 Nov 12.

Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

Objective: To investigate physiological responses to cardiopulmonary exercise (CPX) testing in adults with type 1 diabetes compared with age-, sex-, and BMI-matched control participants without type 1 diabetes.

Research Design And Methods: We compared results from CPX tests on a cycle ergometer in individuals with type 1 diabetes and control participants without type 1 diabetes. Parameters were peak and threshold variables of VO, heart rate, and power output. Differences between groups were investigated through restricted maximum likelihood modeling and post hoc tests. Differences between groups were explained by stepwise linear regressions ( < 0.05).

Results: Among 303 individuals with type 1 diabetes (age 33 [interquartile range 22; 43] years, 93 females, BMI 23.6 [22; 26] kg/m, HbA 6.9% [6.2; 7.7%] [52 (44; 61) mmol/mol]), VO (32.55 [26.49; 38.72] vs. 42.67 ± 10.44 mL/kg/min), peak heart rate (179 [170; 187] vs. 184 [175; 191] beats/min), and peak power (216 [171; 253] vs. 245 [200; 300] W) were lower compared with 308 control participants without type 1 diabetes (all < 0.001). Individuals with type 1 diabetes displayed an impaired degree and direction of the heart rate-to-performance curve compared with control participants without type 1 diabetes (0.07 [-0.75; 1.09] vs. 0.66 [-0.28; 1.45]; < 0.001). None of the exercise physiological responses were associated with HbA in individuals with type 1 diabetes.

Conclusions: Individuals with type 1 diabetes show altered responses to CPX testing, which cannot be explained by HbA. Intriguingly, the participants in our cohort were people with recent-onset type 1 diabetes; heart rate dynamics were altered during CPX testing.
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http://dx.doi.org/10.2337/dc20-1496DOI Listing
January 2021

Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA).

Pediatr Diabetes 2020 12 13;21(8):1375-1393. Epub 2020 Oct 13.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria.

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes.
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http://dx.doi.org/10.1111/pedi.13105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702152PMC
December 2020

Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA).

Diabetologia 2020 12;63(12):2501-2520

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 2, 8036, Graz, Austria.

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (i.e. before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05263-9DOI Listing
December 2020

Epidemiology of major lower extremity amputations in individuals with diabetes in Austria, 2014-2017: A retrospective analysis of health insurance database.

Diabetes Res Clin Pract 2020 Dec 28;170:108477. Epub 2020 Sep 28.

Division of Endocrinology and Diabetology, Department of Medicine, Medical University of Graz, Graz, Austria. Electronic address:

Aims: To describe the incidence, mortality, and trend of major lower extremity amputations (LEA) and to assess risk factors of all-cause mortality after major LEA in individuals with diabetes.

Methods: Procedure codes of major LEA were extracted from the Austrian Health Insurance database (N = 507,180) during 2014-2017 to estimate crude and age-standardized rates per 100,000 population. Short- (30-day, 90-day) and long-term (1-year, 5-year) all-cause mortality after major LEA was estimated from the date of amputation till the date of death.

Results: The age-standardized rate of major LEA was 6.44 with an insignificant annual change of 3% (p = 0.825) from 2014 to 2017. Cumulative 30-day mortality was 13.5%, 90-day 22.0%, 1-year 34.4%, and 5-year 66.7%. Age, male sex, above-knee amputation, Charlson index, and heart failure were significantly associated with both short- and long-term mortality. Cancer, dementia, heart failure, peripheral vascular disease, and renal disease were associated with long-term mortality.

Conclusions: The rate of major LEA in individuals with diabetes remained stable during 2014-2017 in Austria. Short- and long-term mortality rates were considerably high after major LEA. Old age, male sex, above-knee amputations, and Charlson Index were significant predictors of both short- and long-term mortality and comorbidities were significant predictors of long-term mortality only.
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http://dx.doi.org/10.1016/j.diabres.2020.108477DOI Listing
December 2020

Improved glycaemic variability and basal insulin dose reduction during a running competition in recreationally active adults with type 1 diabetes-A single-centre, prospective, controlled observational study.

PLoS One 2020 11;15(9):e0239091. Epub 2020 Sep 11.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Introduction: To investigate the glycaemic response, macronutrient intake and insulin management in people with type 1 diabetes (T1D) compared to healthy individuals around a running competition.

Material And Methods: This was a single-centre, prospective, controlled observational study performed in individuals with T1D and healthy people. 24 people (12 T1D) were included in this study (age: T1D 41±12 vs. healthy 38±6 years, females: 3 vs. 6, BMI: 25.53.0 vs. 22.9±2.8 kg/m2). Both groups received an intermittently scanned continuous glucose monitoring (isCGM; FreeStyle Libre 1, Abbott, USA) system to assess glycaemia 24 hours before, during and 24 hours after a running competition. During this period, participants recorded their food intake and insulin administration. Data were analysed via ANOVA and mixed model analyses with post-hoc testing (p≤0.05).

Results: For overall glycaemic ranges in comparison of groups, significant differences were found for time in range (T1D 63±21% vs. healthy 89±13%, p = 0.001), time above range (TAR) 1 (T1D 21±15% vs. healthy 0±0%, p<0.001) and TAR 2 (T1D 8 [0-16%] vs. healthy 0±0%, p<0.001). When glycaemic variability was assessed, people with T1D had a higher glycaemic variability compared to healthy individuals (p<0.0001). Basal insulin dose was significantly reduced when compared against the regular pre-study basal insulin dose (pre-study 22±6 vs. pre-competition day 11±9 (-50±41%), p = 0.02; competition day 15±5 (-32± 1%)).

Conclusion: People with T1D have impaired glucose responses around a running competition compared to healthy individuals. However, basal insulin dose reductions were sufficient to prevent further dysglycaemia.

Clinical Trial Id: drks.de; DRKS00019886.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239091PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485886PMC
November 2020

Blood levels of microRNAs associated with ischemic heart disease differ between Austrians and Japanese: a pilot study.

Sci Rep 2020 08 12;10(1):13628. Epub 2020 Aug 12.

Division of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

Mortality from ischemic heart disease (IHD) is significantly lower in Japan than in Western countries. The purpose of this study was to investigate differences in circulating microRNA (miRNA) levels related to IHD in Austrians and Japanese. Participants were middle-aged healthy male Austrians (n = 20) and Japanese (n = 20). Total miRNAs in serum from each participant were analyzed using the 3D-Gene miRNA Oligo chip. Twenty-one miRNAs, previously reported as associated with IHD, were compared between Austrians and Japanese. The expression levels of miR-106a-5p, miR-135a-3p, miR-150-3p, miR-16-5p, miR-17-5p. miR-191-5p, miR-320b, miR-451a, miR-486-5p, miR-663b, and miR-92a-3p were significantly higher, while the miR-2861 expression level was significantly lower in Austrians as compared to Japanese. Both in Austrians and Japanese, there were significant positive correlations between serum expression levels of each pair of the above miRNAs except for miR-2861. The expression level of miR-2861 showed significant positive correlations with the expression levels of miR-106a-5p, miR-150-3p, miR-17-5p, miR-486-5p, miR-663b and miR-92a-3p in Austrians but not in Japanese. In pathway analysis, proinflammatory cytokine production in foam cells and collagen synthesis in vascular smooth muscle cells were associated with differentially expressed miRNAs. Difference in miRNA levels may contribute to lower cardiovascular risk in Japan than in Western countries.
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http://dx.doi.org/10.1038/s41598-020-69332-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423897PMC
August 2020

Diabetes mellitus is independently associated with adverse clinical outcome in soft tissue sarcoma patients.

Sci Rep 2020 07 24;10(1):12438. Epub 2020 Jul 24.

Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

Diabetes mellitus (DM) and hyperglycemia are known predictors of adverse outcome in different tumor entities. The present study investigated the effect of DM and pre-surgery blood glucose levels on cancer specific survival (CSS), overall survival (OS), and disease-free survival (DFS) in non-metastatic soft tissue sarcoma (STS) patients. A total of 475 STS patients who underwent curative resection were included in this retrospective study. CSS, DFS, and OS were assessed using Kaplan-Meier curves. The association between pre-existing DM as well as mean pre-surgery blood glucose levels and all 3 survival endpoints was analyzed using Cox-hazard proportional (for OS and DFS) and competing risk regression models (for CSS). In unadjusted analysis, DM was significantly associated with adverse CSS (sub-hazard ratio [SHR]: 2.14, 95% confidence interval [CI] 1.18-3.90, p = 0.013) and OS (hazard ratio [HR]: 2.05, 95% CI 1.28-3.28) and remained significant after adjusting for established prognostic factors (CSS: adjusted SHR 2.33, 95% CI 1.21-4.49, p = 0.012; OS: adjusted HR 1.96, 95% CI 1.17-3.28, p = 0.010), respectively. There was no significant association of DM with DFS (p = 0.149). The mean pre-surgery glucose levels were not significantly associated with inferior outcome (CSS: p = 0.510, OS: p = 0.382 and DFS: p = 0.786). This study shows, that DM represents a negative prognostic factor for clinical outcome in STS patients after curative resection.
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http://dx.doi.org/10.1038/s41598-020-69237-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382498PMC
July 2020

Efficacy of Carbohydrate Supplementation Compared With Bolus Insulin Dose Reduction Around Exercise in Adults With Type 1 Diabetes: A Retrospective, Controlled Analysis.

Can J Diabetes 2020 Dec 22;44(8):697-700. Epub 2020 Mar 22.

Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. Electronic address:

Objectives: Individuals with type 1 diabetes try to manage the risk of exercise-induced hypoglycemia by either pre-exercise/pre-meal bolus insulin dose reductions and/or consuming additional carbohydrates during exercise. Both strategies have proven to be effective in offsetting hypoglycemia, but it remains unclear which one is more beneficial. The aim of this study was to assess the efficacy of carbohydrate supplementation vs bolus insulin dose reduction in prevention of hypoglycemia during moderate-intensity exercise in those with type 1 diabetes.

Methods: This investigation was a retrospective, controlled analysis of 2 independent clinical trials. All participants performed continuous, moderate-intensity cycle ergometer exercise for ∼45 minutes. Two therapy management groups and a control group were compared. Group A was supplemented with 15 to 30 g carbohydrates at a glycemic threshold of 7.0 mmol/L during exercise, group B reduced their individual bolus insulin dose by 50% with their last meal before exercise and group C served as a control.

Results: No hypoglycemic events occurred in group A, whereas 4 events were recorded in groups B (p=0.02) and C (p=0.02).

Conclusions: Carbohydrate supplementation was superior to bolus insulin reduction for prevention of hypoglycemia during exercise in people with type 1 diabetes.
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http://dx.doi.org/10.1016/j.jcjd.2020.03.003DOI Listing
December 2020

Empagliflozin protects heart from inflammation and energy depletion via AMPK activation.

Pharmacol Res 2020 08 17;158:104870. Epub 2020 May 17.

Division of Cardiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address:

Aims: Sodium-glucose co-transporter 2 (SGLT2) were originally developed as kidney-targeting anti-diabetic drugs. However, due to their beneficial cardiac off-target effects (as SGLT2 is not expressed in the heart), these antagonists currently receive intense clinical interest in the context of heart failure (HF) in patients with or without diabetes mellitus (DM). Since the mechanisms by which these beneficial effects are mediated are still unclear yet, inflammation that is present in DM and HF has been proposed as a potential pharmacological intervention strategy. Therefore, we tested the hypothesis that the SGLT2 inhibitor, empagliflozin, displays anti-inflammatory potential along with its glucose-lowering property.

Methods And Results: Lipopolysaccharide (LPS) was used to induce inflammation in vitro and in vivo. In cardiomyocytes and macrophages empagliflozin attenuated LPS-induced TNFα and iNOS expression. Analysis of intracellular signalling pathways suggested that empagliflozin activates AMP kinase (AMPK) in both cell types with or without LPS-treatment. Moreover, the SGLT2 inhibitor increased the expression of anti-inflammatory M2 marker proteins in LPS-treated macrophages. Additionally, empagliflozin-mediated AMPK activation prevented LPS-induced ATP/ADP depletion. In vivo administration of LPS in mice impaired cardiac contractility and aortic endothelial relaxation in response to acetylcholine, whereby co-administration of empagliflozin preserved cardiovascular function. These findings were accompanied by improved cardiac AMPK phosphorylation and ATP/ADP, reduced cardiac iNOS, plasma TNFα and creatine kinase MB levels.

Conclusion: Our data identify a novel cardio protective mechanism of SGLT2 inhibitor, empagliflozin, suggesting that AMPK activation-mediated energy repletion and reduced inflammation contribute to the observed cardiovascular benefits of the drug in HF.
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http://dx.doi.org/10.1016/j.phrs.2020.104870DOI Listing
August 2020

Interpreting the recent consensus on time in range for interstitial glucose right - Or wrong?

Diabetes Res Clin Pract 2020 04 12;162:108106. Epub 2020 Mar 12.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.diabres.2020.108106DOI Listing
April 2020

Agreement between cardiovascular disease risk assessment tools: An application to the United Arab Emirates population.

PLoS One 2020 24;15(1):e0228031. Epub 2020 Jan 24.

Department of Internal Medicine, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.

Introduction: Evidence regarding the performance of cardiovascular disease (CVD) risk assessment tools is limited in the United Arab Emirates (UAE). Therefore, we assessed the agreement between various externally validated CVD risk assessment tools in the UAE.

Methods: A secondary analysis of the Abu Dhabi Screening Program for Cardiovascular Risk Markers (AD-SALAMA) data, a large population-based cross-sectional survey conducted in Abu Dhabi, UAE during the period 2009 until 2015, was performed in July 2019. The analysis included 2,621 participants without type 2 Diabetes and without history of cardiovascular diseases. The CVD risk assessment tools included in the analysis were the World Health Organization for Middle East and North Africa Region (WHO-MENA), the systematic coronary risk evaluation for high risk countries (SCORE-H), the pooled cohort risk equations for white (PCRE-W) and African Americans (PCRE-AA), the national cholesterol education program Framingham risk score (FRAM-ATP), and the laboratory Framingham risk score (FRAM-LAB).

Results: The overall concordance coefficient was 0.50. The agreement between SCORE-H and PCRE-W, PCRE-AA, FRAM-LAB, FRAM-ATP and WHO-MENA, were 0.47, 0.39, 0.0.25, 0.42 and 0.18, respectively. PCRE-AA classified the highest proportion of participants into high-risk category of CVD (16.4%), followed by PCRE-W (13.6%), FRAM-LAB (6.9%), SCORE-H (4.5%), FRAM-ATP (2.7%), and WHO-MENA (0.4%).

Conclusions: We found a poor agreement between various externally validated CVD risk assessment tools when applied to a large data collected in the UAE. This poses a challenge to choose any of these tools for clinical decision-making regarding the primary prevention of CVD in the country.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228031PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980489PMC
April 2020

Type 1 Diabetes and Physical Exercise: Moving (forward) as an Adjuvant Therapy.

Curr Pharm Des 2020 ;26(9):946-957

Exercise Physiology, Training & Training Therapy Research Group, Institute of Sports Science, University of Graz, Graz, Austria.

Type 1 diabetes is characterized by an autoimmune β-cell destruction resulting in endogenous insulin deficiency, potentially leading to micro- and macrovascular complications. Besides an exogenous insulin therapy and continuous glucose monitoring, physical exercise is recommended in adults with type 1 diabetes to improve overall health. The close relationship between physical exercise, inflammation, muscle contraction, and macronutrient intake has never been discussed in detail about type 1 diabetes. The aim of this narrative review was to detail the role of physical exercise in improving clinical outcomes, physiological responses to exercise and different nutrition and therapy strategies around exercise. Physical exercise has several positive effects on glucose uptake and systemic inflammation in adults with type 1 diabetes. A new approach via personalized therapy adaptations must be applied to target beneficial effects on complications as well as on body weight management. In combination with pre-defined macronutrient intake around exercise, adults with type 1 diabetes can expect similar physiological responses to physical exercise, as seen in their healthy counterparts. This review highlights interesting findings from recent studies related to exercise and type 1 diabetes. However, there is limited research available accompanied by a proper number of participants in the cohort of type 1 diabetes. Especially for this group of patients, an increased understanding of the impact of physical exercise can improve its effectiveness as an adjuvant therapy to move (forward).
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http://dx.doi.org/10.2174/1381612826666200108113002DOI Listing
November 2020

Impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction-The EMMY trial.

Am Heart J 2020 03 12;221:39-47. Epub 2019 Dec 12.

Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Diabetology, Graz, Austria.

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors are established antidiabetic drugs with proven cardiovascular benefit. Although growing evidence suggests beneficial effects on myocardial remodeling, fluid balance and cardiac function, the impact of empagliflozin initiated early after acute myocardial infarction (AMI) has not been investigated yet. Therefore, the impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction (EMMY) trial was designed to investigate the efficacy and safety of empagliflozin in diabetic and non-diabetic patients after severe AMI.

Methods: Within a multicenter, randomized, double-blind, placebo-controlled, phase 3b trial we will enroll patients with AMI and characteristics suggestive of severe myocardial necrosis are randomized in a 1:1 ratio to empagliflozin (10 mg once daily) or matching placebo. The primary endpoint is the impact of empagliflozin on changes in NT-proBNP within 6 months after AMI. Secondary endpoints include changes in echocardiographic parameters, levels of ketone body concentrations, HbA1c levels and body weight, respectively. Hospitalization rate due to heart failure or other causes, the duration of hospital stay and all-cause mortality will be assessed as exploratory secondary endpoints.

Discussion: The EMMY trial will test empagliflozin in patients with AMI regardless of their diabetic status. The EMMY trial may therefore underpin the concept of SGLT2 inhibition to improve cardiac remodeling, pre-and afterload reduction and cardiac metabolism regardless of its antidiabetic effects. Results will provide the rationale for the conduct of a cardiovascular outcome trial to test the effect of empagliflozin in patients with AMI.
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http://dx.doi.org/10.1016/j.ahj.2019.12.004DOI Listing
March 2020

Effects of a multispecies synbiotic on glucose metabolism, lipid marker, gut microbiome composition, gut permeability, and quality of life in diabesity: a randomized, double-blind, placebo-controlled pilot study.

Eur J Nutr 2020 Oct 15;59(7):2969-2983. Epub 2019 Nov 15.

Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

Purpose: Diabesity, the combination of obesity and type 2 diabetes, is an ever-growing global health burden. Diabesity-associated dysbiosis of the intestinal microbiome has gained attention as a potential driver of disease and, therefore, a possible therapeutic target by means of pro- or prebiotic supplementation. This study tested the effects of a multispecies synbiotic (i.e. a combination of probiotics and prebiotics) on glucose metabolism, gut microbiota, gut permeability, neutrophil function and quality of life in treatment-experienced diabesity patients.

Methods: A randomized, double-blind, placebo-controlled pilot study with 26 diabesity patients was conducted in which patients received a daily dose of a multispecies probiotic and a prebiotic (or a placebo) for 6 months.

Results: There were no changes in glucose metabolism or mixed meal tolerance test responses throughout the study. The analysis of secondary outcomes revealed beneficial effects on hip circumference [- 1 (95% CI - 4; 3) vs +3 (- 1; 8) cm, synbiotics vs. placebo, respectively, p = 0.04], serum zonulin [- 0.04 (- 0.2; 0.1) vs +0.3 (- 0.05; 0.6) ng/ml, p = 0.004)] and the physical role item of the SF36 quality of life assessment [+ 5.4 (- 1.7; 12.5) vs - 5.0 (- 10.1; 0.2) points, p = 0.02] after 3 months of intervention, and lipoprotein (a) [- 2.1 (- 5.7; 1.6) vs +3.4 (- 0.9; 7.9) mg/dl, p = 0.02] after 6 months. There were no significant differences in alpha or beta diversity of the microbiome between groups or time points.

Conclusions: Glucose metabolism as the primary outcome was unchanged during the intervention with a multispecies synbiotic in patients with diabesity. Nevertheless, synbiotics improved some symptoms and biomarkers of type 2 diabetes and aspects of quality of life suggesting a potential role as adjuvant tool in the management of diabesity.
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http://dx.doi.org/10.1007/s00394-019-02135-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501130PMC
October 2020

Hypoglycaemia leads to a delayed increase in platelet and coagulation activation markers in people with type 2 diabetes treated with metformin only: Results from a stepwise hypoglycaemic clamp study.

Diabetes Obes Metab 2020 02 3;22(2):212-221. Epub 2019 Nov 3.

Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.

Aims: To investigate the effect of hypoglycaemia on platelet and coagulation activation in people with type 2 diabetes.

Materials And Methods: This monocentric, open, single-arm, mechanistic trial included 14 people with established type 2 diabetes (four women, 10 men, age 55 ± 7 years, glycated haemoglobin concentration 51 ± 7 mmol/mol) receiving metformin monotherapy. A stepwise hyperinsulinaemic-hypoglycaemic clamp experiment (3.5 and 2.5 mmol/L, for 30 minutes respectively) was performed, aiming to investigate platelet and coagulation activity during predefined plateaus of hypoglycaemia, as well as 1 day and 7 days later.

Results: While platelet activation assessed by light transmittance aggregometry did not significantly increase after the hypoglycaemic clamp procedure, the more sensitive flow cytometry-based measurement of platelet surface activation markers showed hypoglycaemia-induced activation 24 hours (PAC1 CD62P , PAC1 CD63P and PAC1 CD62P CD63 ; P < .01) and 7 days after the hypoglycaemic clamp (P < .001 for PAC1 CD63 ; P < .01 for PAC1 CD62P and PAC1 CD62P CD63 ) in comparison to baseline. Coagulation markers, such as fibrinogen, D-dimer, plasminogen activator inhibitor-1, von Willebrand factor activity and factor VIII, were also significantly increased, an effect that was most pronounced 24 hours after the hypoglycaemic clamp.

Conclusion: A single event of insulin-induced hypoglycaemia led to an increase in markers of platelet activation and coagulation in people with early stages of type 2 diabetes on metformin therapy. However, the activation occurred with a delay and was evident 24 hours and 7 days after the actual hypoglycaemic episode.
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http://dx.doi.org/10.1111/dom.13889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972619PMC
February 2020

Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans.

Cell Metab 2019 09 27;30(3):462-476.e6. Epub 2019 Aug 27.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria; HEALTH Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstraße 2, Graz, Austria.

Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.
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http://dx.doi.org/10.1016/j.cmet.2019.07.016DOI Listing
September 2019

[Correction to: Therapie der akuten diabetischen Stoffwechselentgleisungen bei Erwachsenen (Update 2019)].

Wien Klin Wochenschr 2019 Aug;131(15-16):389

Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich.

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http://dx.doi.org/10.1007/s00508-019-01536-5DOI Listing
August 2019

The future is now: SGLT2 inhibitors and type 1 diabetes - What about exercise?

Diabetes Res Clin Pract 2019 09 1;155:107806. Epub 2019 Aug 1.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

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http://dx.doi.org/10.1016/j.diabres.2019.107806DOI Listing
September 2019

Performance of the Freestyle Libre flash glucose monitoring (flash GM) system in individuals with type 1 diabetes: A secondary outcome analysis of a randomized crossover trial.

Diabetes Obes Metab 2019 11 5;21(11):2505-2512. Epub 2019 Aug 5.

Diabetes Research Group, Medical School, Swansea University, Swansea, UK.

Aims: The efficacy of flash glucose monitoring (flash GM) systems has been demonstrated by improvements in glycaemia; however, during high rates of glucose flux, the performance of continuous glucose monitoring systems was impaired, as detailed in previous studies. This study aimed to determine the performance of the flash GM system during daily-life glycaemic challenges such as carbohydrate-rich meals, bolus insulin-induced glycaemic disturbances and acute physical exercise in individuals with type 1 diabetes.

Materials And Methods: This study comprised four randomized trial visits with alternating pre- and post-exercise bolus insulin doses. Throughout the four 14-hour inpatient phases, 19 participants received three carbohydrate-rich meals and performed moderate-intensity exercise. Venous blood glucose and capillary blood glucose during exercise was compared to interstitial glucose concentrations. Flash GM accuracy was assessed by median absolute relative difference (MARD) (interquartile range [IQR]) using the Bland-Altman method and Clark error grid, as well as according to guidelines for integrated CGM approvals (Class II-510(K)).

Results: The overall MARD (IQR) during inpatient phases was 14.3% (6.9%-22.8%), during hypoglycaemia (≤3.9 mmol/L) was 31.6% (16.2%-46.8%), during euglycaemia (4.0 mmol/L - 9.9 mmol/L) was 16.0% (8.5%-24.0%) and during hyperglycaemia (≥10 mmol/L) was 9.4% (5.1%-15.7%). Overall Bland-Altman analysis showed a bias (95% LoA) of 1.26 mmol/L (-1.67 to 4.19 mmol/L). The overall MARD during acute exercise was 29.8% (17.5%-39.8%), during hypoglycaemia was 45.1% (35.2%-51.1%), during euglycaemia was 30.7% (18.7%-39.2%) and during hyperglycaemia was 16.3% (10.0%-22.8%).

Conclusion: Flash GM interstitial glucose readings were not sufficiently accurate within the hypoglycaemic range and during acute exercise and require confirmatory blood glucose measurements.
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http://dx.doi.org/10.1111/dom.13835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852439PMC
November 2019