Publications by authors named "Lars Stechemesser"

17 Publications

  • Page 1 of 1

Apolipoprotein C-III predicts cardiovascular events and mortality in individuals with type 1 diabetes and albuminuria.

J Intern Med 2021 Nov 24. Epub 2021 Nov 24.

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.

Objectives: We studied apolipoprotein C-III (apoC-III) in relation to diabetic kidney disease (DKD), cardiovascular outcomes, and mortality in type 1 diabetes.

Methods: The cohort comprised 3966 participants from the prospective observational Finnish Diabetic Nephropathy Study. Progression of DKD was determined from medical records. A major adverse cardiac event (MACE) was defined as acute myocardial infarction, coronary revascularization, stroke, or cardiovascular mortality through 2017. Cardiovascular and mortality data were retrieved from national registries.

Results: ApoC-III predicted DKD progression independent of sex, diabetes duration, blood pressure, HbA , smoking, LDL-cholesterol, lipid-lowering medication, DKD category, and remnant cholesterol (hazard ratio [HR] 1.43 [95% confidence interval 1.05-1.94], p = 0.02). ApoC-III also predicted the MACE in a multivariable regression analysis; however, it was not independent of remnant cholesterol (HR 1.05 [0.81-1.36, p = 0.71] with remnant cholesterol; 1.30 [1.03-1.64, p = 0.03] without). DKD-specific analyses revealed that the association was driven by individuals with albuminuria, as no link between apoC-III and the outcome was observed in the normal albumin excretion or kidney failure categories. The same was observed for mortality: Individuals with albuminuria had an adjusted HR of 1.49 (1.03-2.16, p = 0.03) for premature death, while no association was found in the other groups. The highest apoC-III quartile displayed a markedly higher risk of MACE and death than the lower quartiles; however, this nonlinear relationship flattened after adjustment.

Conclusions: The impact of apoC-III on MACE risk and mortality is restricted to those with albuminuria among individuals with type 1 diabetes. This study also revealed that apoC-III predicts DKD progression, independent of the initial DKD category.
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http://dx.doi.org/10.1111/joim.13412DOI Listing
November 2021

Idiopathic Frozen Shoulder in Individuals with Diabetes: Association with Metabolic Control, Obesity, Antidiabetic Treatment and Demographic Characteristics in Adults with Type 1 or 2 Diabetes from the DPV Registry.

Exp Clin Endocrinol Diabetes 2021 Aug 23. Epub 2021 Aug 23.

Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany.

Aims: To examine the association of frozen shoulder (FS) with demographic and diabetes-related outcomes in individuals with type 1 (T1D) or type 2 (T2D) diabetes aged ≥30 years.

Materials And Methods: Multivariable logistic regression models, adjusted for demographics were used to calculate the proportion of FS in association with age, gender, diabetes duration, body mass index (BMI), haemoglobin A1C (HbA1c) and diabetes treatment.

Results: The unadjusted percentage of FS was higher in T1D compared to T2D (0.22% vs. 0.06%). In T1D, adjusted regression models revealed higher prevalence of FS in women than men (0.26 [0.20-0.34] % vs. 0.15 [0.11-0.21] %, =0.010). No significant relationship of age and BMI with FS was found in both diabetes types. Longer diabetes duration was associated with a higher proportion of FS in T1D <0.001) and T2D (=0.004). In T1D, HbA1c >7% was related to a higher proportion of FS compared to HbA1c ≤7% (0.25 [0.19-0.32] vs. 0.12 [0.08-0.20] %, =0.007), while an inverse relationship was found in T2D (HbA1c ≤7%: 0.08 [0.07-0.10] vs. HbA1c >7%: 0.05 [0.04-0.06] %, =0.001).

Conclusions: Different associations of FS with gender and HbA1c were observed for T1D and T2D; however, longer diabetes duration increases the risk for FS independent of diabetes type. Musculoskeletal diseases are still underreported in individuals with diabetes and awareness should be raised for FS as a specific diabetes complication.
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http://dx.doi.org/10.1055/a-1543-8559DOI Listing
August 2021

Demographic characteristics and acute complications among adults with type 1 diabetes: Comparison of two multicentre databases from Germany and the United States.

J Diabetes Complications 2021 03 26;35(3):107812. Epub 2020 Nov 26.

Real World Evidence and Clinical Outcome Generation, Sanofi, Paris, France.

Background: Studies on acute complications in adult T1D were previously reported from the United States (U.S.) and from Germany. The aim was to compare demographic characteristics and patterns of severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA) between Germany and the U.S.

Methods: Descriptive comparison on individuals aged ≥18 years, with T1D duration ≥2 years were made between the German diabetes-patient registry (DPV) and the U.S. electronic-health-record database (T1PCO). Individuals in both databases were divided into patients with haemoglobin A1c (HbA1c) <7% and HbA1c ≥7%.

Results: 5190 (DPV) and 31,430 individuals (T1PCO) fulfilled the inclusion criteria. DPV patients were younger, more often male and had lower body-mass index. In both databases, more males than females had HbA1c <7%. Individuals had higher HbA1c in T1PCO compared to DPV. The relationship between HbA1c and DKA was similar in both databases. SH revealed a U-shaped curve in T1PCO, but no clear pattern was present in DPV. SH events increased with higher age in DPV, but not in T1PCO.

Conclusion: Patterns of SH differ between Germany and U.S. Differences in capture of SH among the databases cannot be excluded, but differences in health care including patient education and level of care by specialists are likely.
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http://dx.doi.org/10.1016/j.jdiacomp.2020.107812DOI Listing
March 2021

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

Reducing the probability of falsely elevated HbA1c results in diabetic patients by applying automated and educative HbA1c re-testing intervals.

Clin Biochem 2020 Jun 27;80:14-18. Epub 2020 Mar 27.

Department of Laboratory Medicine, Paracelsus Medical University Salzburg, Müllner Hauptstrasse 48, A-5020 Salzburg, Austria. Electronic address:

Introduction: Too frequent HbA1c measurements may lead to unnecessary treatment modifications of diabetic patients. The aim of this study was to estimate the percentage of falsely elevated HbA1c results in two hospitals, Landeskrankenhaus/Uniklinikum Salzburg (LKH) and Landesklinik St. Veit (STV), as well as to retrospectively investigate the effect of an automated and an educative 60-day re-testing interval (RTI).

Methods: The amount of estimated falsely elevated results (eFER), based on odds calculated using the baseline and the follow-up values and the time between these measurements, the number of HbA1c re-testings within 60 days as well as the overall number of ordered and performed HbA1c analyses were calculated. In LKH, an automated algorithm cancelling inappropriate HbA1c testing was applied, and in STV, educational actions were taken.

Results: Before RTI-implementation, eFER were 0.9% and 2.1% and within-60-days-re-testing were 15.0% and 7.4% of cases in LKH and STV, respectively. After RTI-implementation, these numbers decreased to 0.2% (p < .001) and 1.8% (p = .869) and within-60-days-re-testing decreased to 1.1% (p < .001) and 3.6% (p = .003) in LKH and STV, respectively. Median monthly HbA1c measurements decreased by 15.8% (p < .001) and 21.1% (p = .002) in LKH and STV, respectively.

Conclusion: Both the educational and the automated 60-day-RTI were proven to be efficient in reducing overall HbA1c measurements, re-testing within 60 days and eFER.
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http://dx.doi.org/10.1016/j.clinbiochem.2020.03.014DOI Listing
June 2020

Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen.

J Am Soc Nephrol 2019 10 19;30(10):2000-2016. Epub 2019 Sep 19.

Department of Biostatistics and.

Background: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown.

Methods: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function.

Results: Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain ( gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition ( or renal biology ( and ).

Conclusions: The 16 diabetic kidney disease-associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.
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http://dx.doi.org/10.1681/ASN.2019030218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779358PMC
October 2019

[Hospital diabetes management (Update 2019)].

Wien Klin Wochenschr 2019 May;131(Suppl 1):200-211

Klinische Abteilung für Endokrinologie und Diabetologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Auenbruggerplatz 15, 8036, Graz, Österreich.

This position statement presents the recommendations of the Austrian Diabetes Association for diabetes management of adult patients during inpatient stay. It is based on the current evidence with respect to blood glucose targets, insulin therapy and treatment with oral antidiabetic drugs during inpatient hospitalization. Additionally, special circumstances such as intravenous insulin therapy, concomitant therapy with glucocorticoids and use of diabetes technology during hospitalization are discussed.
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http://dx.doi.org/10.1007/s00508-019-1447-zDOI Listing
May 2019

[Blood glucose self monitoring (Update 2019)].

Wien Klin Wochenschr 2019 May;131(Suppl 1):115-118

Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich.

Self monitoring of blood glucose contributes to the integrated management of diabetes mellitus. It, thus, should be available for all patients with diabetes mellitus. Self monitoring of blood glucose improves patients safety, quality of life and glucose control. The current article represents the recommendations of the Austrian Diabetes Association for the use of blood glucose self monitoring according to current scientific evidence.
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http://dx.doi.org/10.1007/s00508-018-1436-7DOI Listing
May 2019

[Antihyperglycemic treatment guidelines for diabetes mellitus type 2 (Update 2019)].

Wien Klin Wochenschr 2019 May;131(Suppl 1):27-38

Klinische Abteilung für Endokrinologie und Diabetologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Graz, Österreich.

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.
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http://dx.doi.org/10.1007/s00508-019-1471-zDOI Listing
May 2019

[Insulin therapy of type 2 diabetes mellitus (Update 2019)].

Wien Klin Wochenschr 2019 May;131(Suppl 1):39-46

Klinische Abteilung für Endokrinologie und Diabetologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Graz, Österreich.

The present article is a recommendation of the Austrian Diabetes Association for the practical use of insulin in type 2 diabetes, including the various insulin regimens.
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http://dx.doi.org/10.1007/s00508-019-1492-7DOI Listing
May 2019

Clinical implications of fetuin-A.

Adv Clin Chem 2019;89:79-130. Epub 2019 Feb 8.

Department of Internal Medicine I, Divisions of Nephrology and Endocrinology, Paracelsus Medical University, Salzburg, Austria.

Fetuin-A, also termed alpha2-Heremans-Schmid glycoprotein, is a 46kDa hepatocyte derived protein (hepatokine) and serves multifaceted functions.
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http://dx.doi.org/10.1016/bs.acc.2018.12.003DOI Listing
May 2019

Lean Patients with Non-Alcoholic Fatty Liver Disease Have a Severe Histological Phenotype Similar to Obese Patients.

J Clin Med 2018 Dec 17;7(12). Epub 2018 Dec 17.

First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.

A small proportion of lean patients develop non-alcoholic fatty liver disease (NAFLD). We aimed to report the histological picture of lean NAFLD in comparison to overweight and obese NAFLD patients. Biopsy and clinical data from 466 patients diagnosed with NAFLD were stratified to groups according to body mass index (BMI): lean (BMI ≤ 25.0 kg/m², confirmed to be appropriate = 74), overweight (BMI > 25.0 ≤ 30.0 kg/m², = 242) and obese (BMI > 30.0 kg/m², = 150). Lean NAFLD patients had a higher rate of lobular inflammation compared to overweight patients (12/74; 16.2% vs. 19/242; 7.9%; = 0.011) but were similar to obese patients (25/150; 16.7%). Ballooning was observed in fewer overweight patients (38/242; 15.7%) compared to lean (19/74; 25.7%; = 0.014) and obese patients (38/150; 25.3%; = 0.006). Overweight patients had a lower rate of portal and periportal fibrosis (32/242; 13.2%) than lean (19/74; 25.7%; = 0.019) and obese patients (37/150; 24.7%; = 0.016). The rate of cirrhosis was higher in lean patients (6/74; 8.1%) compared to overweight (4/242; 1.7%; = 0.010) and obese patients (3/150; 2.0% = 0.027). In total, 60/466; 12.9% patients were diagnosed with non-alcoholic steatohepatitis (NASH). The rate of NASH was higher in lean (14/74; 18.9% = 0.01) and obese (26/150; 17.3%; = 0.007) compared to overweight patients (20/242; 8.3%)). Among lean patients, fasting glucose, INR and use of thyroid hormone replacement therapy were independent predictors of NASH in a multivariate model. Lean NAFLD patients were characterized by a severe histological picture similar to obese patients but are more progressed compared to overweight patients. Fasting glucose, international normalized ratio (INR) and the use of thyroid hormone replacement may serve as indicators for NASH in lean patients.
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http://dx.doi.org/10.3390/jcm7120562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306845PMC
December 2018

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism.

Mol Metab 2017 01 31;6(1):38-47. Epub 2016 Oct 31.

First Department of Medicine, Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria; Obesity Research Unit, Paracelsus Medical University, Müllner Hauptstrasse 48, 5020 Salzburg, Austria. Electronic address:

Objective: Elevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways.

Methods: In a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1) lean, healthy controls (n = 53), (2) MetS without hyperferritinemia (n = 54) and (3) MetS with hyperferritinemia (n = 56). An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach.

Results: Subjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001), HbA1c (p = 0.035) and 1 h glucose in oral glucose tolerance test (p = 0.002) compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites).

Conclusions: Our data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.
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http://dx.doi.org/10.1016/j.molmet.2016.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220278PMC
January 2017

[Blood glucose self monitoring].

Wien Klin Wochenschr 2016 Apr;128 Suppl 2:S137-40

Universitätsklinik für Innere Medizin I, Landeskrankenhaus Salzburg - Universitätsklinikum, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich.

Self monitoring of blood glucose contributes to the integrated management of diabetes mellitus. It, thus, should be available for all patients with diabetes mellitus type-1 and type-2. Self monitoring of blood glucose improves patients safety, quality of life and glucose control. The current article represents the recommendations of the Austrian Diabetes Association for the use of blood glucose self monitoring according to current scientific evidence.
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http://dx.doi.org/10.1007/s00508-015-0927-zDOI Listing
April 2016

Training of carbohydrate estimation for people with diabetes using mobile augmented reality.

J Diabetes Sci Technol 2015 May 16;9(3):516-24. Epub 2015 Apr 16.

Department of MultiMediaTechnology, Salzburg University of Applied Sciences, Puch, Austria

Background: Imprecise carbohydrate counting as a measure to guide the treatment of diabetes may be a source of errors resulting in problems in glycemic control. Exact measurements can be tedious, leading most patients to estimate their carbohydrate intake. In the presented pilot study a smartphone application (BE(AR)), that guides the estimation of the amounts of carbohydrates, was used by a group of diabetic patients.

Methods: Eight adult patients with diabetes mellitus type 1 were recruited for the study. At the beginning of the study patients were introduced to BE(AR) in sessions lasting 45 minutes per patient. Patients redraw the real food in 3D on the smartphone screen. Based on a selected food type and the 3D form created using BE(AR) an estimation of carbohydrate content is calculated. Patients were supplied with the application on their personal smartphone or a loaner device and were instructed to use the application in real-world context during the study period. For evaluation purpose a test measuring carbohydrate estimation quality was designed and performed at the beginning and the end of the study.

Results: In 44% of the estimations performed at the end of the study the error reduced by at least 6 grams of carbohydrate. This improvement occurred albeit several problems with the usage of BE(AR) were reported.

Conclusions: Despite user interaction problems in this group of patients the provided intervention resulted in a reduction in the absolute error of carbohydrate estimation. Intervention with smartphone applications to assist carbohydrate counting apparently results in more accurate estimations.
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http://dx.doi.org/10.1177/1932296815578880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604528PMC
May 2015

Intraindividual differences between two simultaneous glucose measurement systems in type 2 diabetic patients.

Wien Klin Wochenschr 2012 Jul 6;124(13-14):453-60. Epub 2012 Jul 6.

Department of Internal Medicine I, Paracelsus Medical University Clinic Salzburg, Müllner Hauptstrasse 48, 5020, Salzburg, Austria.

Aims: Continuous glucose measurement systems are an established tool to support diabetes therapy. Because of different technical solutions one can propose different potential limitations in daily practice. So we tried to identify the accuracy of two different devices head to head in daily routine to point out individual characteristics.

Methods: We included 24 patients with type 2 diabetes mellitus to wear the GlucoDay and the MiniMed continuous glucose measurement system at the same time for 48 h. We examined the mean differences in simultaneous glucose measurements, the confidence intervals were calculated by standard methods based on the t-distribution.

Results: Comparison of glucose levels of both continuous glucose measurement systems showed that there was a tendency for higher glucose levels measured by the GlucoDay device. These differences were dependent on the time of the day. The absolute difference between two consecutive glucose measurements was higher for the GlucoDay system what means a somehow higher fluctuation of the GlucoDay measurements.

Conclusions: The differences in intraindividual comparison of the GlucoDay and the MiniMed continuous glucose measurement systems in type 2 diabetic patients may be taken into account when using different systems for detection of nocturnal hypoglycemia and the observation of trends used for therapeutic decisions.
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http://dx.doi.org/10.1007/s00508-012-0201-6DOI Listing
July 2012
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