Search tips
Search criteria

Results 1-10 (10)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Increased DNA Dicarbonyl Glycation and Oxidation Markers in Patients with Type 2 Diabetes and Link to Diabetic Nephropathy 
Journal of Diabetes Research  2015;2015:915486.
Aim. The aim of this study was to assess the changes of markers of DNA damage by glycation and oxidation in patients with type 2 diabetes and the association with diabetic nephropathy. Methodology. DNA oxidation and glycation adducts were analysed in plasma and urine by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. DNA markers analysed were as follows: the oxidation adduct 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-OxodG) and glycation adducts of glyoxal and methylglyoxal—imidazopurinones GdG, MGdG, and N2-(1,R/S-carboxyethyl)deoxyguanosine (CEdG). Results. Plasma 8-OxodG and GdG were increased 2-fold and 6-fold, respectively, in patients with type 2 diabetes, with respect to healthy volunteers. Median urinary excretion rates of 8-OxodG, GdG, MGdG, and CEdG were increased 28-fold, 10-fold, 2-fold, and 2-fold, respectively, in patients with type 2 diabetes with respect to healthy controls. In patients with type 2 diabetes, nephropathy was associated with increased plasma 8-OxodG and increased urinary GdG and CEdG. In a multiple logistic regression model for diabetic nephropathy, diabetic nephropathy was linked to systolic blood pressure and urinary CEdG. Conclusion. DNA oxidative and glycation damage-derived nucleoside adducts are increased in plasma and urine of patients with type 2 diabetes and further increased in patients with diabetic nephropathy.
PMCID: PMC4408631  PMID: 25950009
2.  Evaluation of a Self-Administered Oral Glucose Tolerance Test 
Diabetes Care  2013;36(6):1483-1488.
To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting.
Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink.
The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order.
Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes.
PMCID: PMC3661807  PMID: 23321216
4.  Multiple risk factor intervention reduces carotid atherosclerosis in patients with type 2 diabetes 
Patients with rapid progression of carotid intima media thickness (CIMT) were shown to have a higher future risk for cardiovascular events.
The aim of this study was to investigate the impact of multiple risk factor intervention on CIMT progression and to establish whether new cardiovascular surrogate measurements would allow prediction of CIMT changes.
Materials and methods
In this prospective, open, 2-years study, we included 97 patients with type 2 diabetes and at least two insufficiently treated cardiovascular risk factors, i.e. HbA1c > 7.5% (58 mmol/mol); LDL-cholesterol >3.1 mmol/l or blood pressure >140/90 mmHg. Treatment was intensified according to current guidelines over 3 months with the aim to maintain intensification over 2 years.
The primary outcome was the change in CIMT after 2 years. We also assessed markers of mechanical and biochemical endothelial function and endothelial progenitor cells before and after 3 months of treatment intensification. For testing differences between before and after multifactorial treatment measurements we used either the paired student’s t-test or the Wilcoxon signed-rank test, depending on the distribution of the data. Additional, explorative statistical data analysis was done on CIMT progression building a linear multivariate regression model.
Blood glucose, lipids and blood pressure significantly improved during the first 3 months of intensified treatment, which was sustained over the 2-year study duration. Mean CIMT significantly decreased from baseline to 2 year (0.883 ± 0.120 mm vs. 0.860 ± 0.130 mm; p = 0.021). None of the investigated surrogate measures, however, was able to predict changes in IMT early after treatment intensification.
Intensification of risk factor intervention in type 2 diabetes results in CIMT regression over a period of 2 years. None of the biomarkers used including endothelial function parameters or endothelial progenitor cells turned out to be useful to predict CIMT changes.
Trial registration
Clinical Trial Registration – Unique identifier: NCT00660790
PMCID: PMC4041351  PMID: 24884694
Intensified risk factor intervention; Carotid intima media thickness; Type 2 diabetes; Cardiovascular surrogate measurements; Carotid atherosclerosis
5.  A Pan-European and Canadian Prospective Survey to Evaluate Patient Satisfaction with the SoloSTAR Insulin Injection Device in Type 1 and Type 2 Diabetes 
This study evaluated patient satisfaction with SoloSTAR® (sanofi-aventis), a prefilled insulin pen device for injection of insulin glargine or insulin glulisine.
This was a 6–8-week multicenter (n = 652), observational, prospective Pan-European and Canadian registry study in patients with diabetes mellitus (n = 6542) who recently switched to or started treatment with insulin glargine and/or insulin glulisine using SoloSTAR or were insulin naïve. At the baseline visit, patients were asked to evaluate their satisfaction with their previous device, if applicable. After 6–8 weeks of SoloSTAR use, patients were asked to rate their satisfaction.
Overall, 6481 patients (mean age 54 years, 48.7% male, 72% type 2 diabetes) were analyzed in this study. Of these, 4995 (77.1%) patients had used insulin before the study and 1641 (32.9%) and 3395 (68.0%) patients had previously used prefilled and/or reusable pens, respectively. During the study, SoloSTAR was used to administer insulin glargine and/or insulin glulisine by 97.3% and 36.0% of patients, respectively (both: 27.0%). Most patients rated SoloSTAR as “excellent/good” for ease of use (97.9%), learning to use (98.3%), selecting the dose (97.6%), and reading the dose (95.1%). Most patients rated ease of use (88.4%) and injecting a dose (84.5%) with SoloSTAR as “much easier/easier” versus their previous pen. Overall, 98% planned to continue using SoloSTAR. No safety concerns were reported.
This European and Canadian survey shows that SoloSTAR was well accepted in this large patient population. Most patients preferred SoloSTAR to their previous pen and planned to continue SoloSTAR use.
PMCID: PMC3208886  PMID: 22027323
European; insulin glargine; insulin glulisine; insulin pen device; patient satisfaction; SoloSTAR
6.  Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study 
Critical Care  2011;15(2):R104.
Vitamin D deficiency is encountered frequently in critically ill patients and might be harmful. Current nutrition guidelines recommend very low vitamin D doses. The objective of this trial was to evaluate the safety and efficacy of a single oral high-dose vitamin D3 supplementation in an intensive care setting over a one-week observation period.
This was a randomized, double-blind, placebo-controlled pilot study in a medical ICU at a tertiary care university center in Graz, Austria. Twenty-five patients (mean age 62 ± 16yrs) with vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) ≤20 ng/ml] and an expected stay in the ICU >48 hours were included and randomly received either 540,000 IU (corresponding to 13.5 mg) of cholecalciferol (VITD) dissolved in 45 ml herbal oil or matched placebo (PBO) orally or via feeding tube.
The mean serum 25(OH)D increase in the intervention group was 25 ng/ml (range 1-47 ng/ml). The highest 25(OH)D level reached was 64 ng/ml, while two patients showed a small (7 ng/ml) or no response (1 ng/ml). Hypercalcemia or hypercalciuria did not occur in any patient. From day 0 to day 7, total serum calcium levels increased by 0.10 (PBO) and 0.15 mmol/L (VITD; P < 0.05 for both), while ionized calcium levels increased by 0.11 (PBO) and 0.05 mmol/L (VITD; P < 0.05 for both). Parathyroid hormone levels decreased by 19 and 28 pg/ml (PBO and VITD, ns) over the seven days, while 1,25(OH)D showed a transient significant increase in the VITD group only.
This pilot study shows that a single oral ultra-high dose of cholecalciferol corrects vitamin D deficiency within 2 days in most patients without causing adverse effects like hypercalcemia or hypercalciuria. Further research is needed to confirm our results and establish whether vitamin D supplementation can affect the clinical outcome of vitamin D deficient critically ill patients.
EudraCT Number
German Clinical Trials Register (DRKS)
PMCID: PMC3219377  PMID: 21443793
7.  Chronic TNF-α Neutralization Does Not Improve Insulin Resistance or Endothelial Function in “Healthy” Men with Metabolic Syndrome 
Molecular Medicine  2010;17(3-4):189-193.
The possible contribution of tumor necrosis factor-α (TNF-α) to the development of obesity-associated insulin resistance in humans is still controversial. Our study investigated the effect of TNF-α neutralization on insulin resistance in healthy, obese and insulin resistant men. We performed a prospective, randomized, double-blind placebo-controlled trial in nine young, healthy obese male subjects with metabolic syndrome and insulin resistance. Volunteers received three infusions (wks 0, 2 and 6) of infliximab or placebo. Insulin resistance was measured at baseline and after 70 d by homeostatic model assessment (HOMA) index as well as by minimal model analysis of an intravenous glucose tolerance test. Endothelial function was accessed before and after intervention by flow mediated dilation. Infliximab improved the inflammatory status as indicated by reduced high sensitivity C-reactive protein (hsCRP) and fibrinogen levels (2.77 ± 0.6 to 1.8 ± 0.5 μg/L, and 3.42 ± 0.18 to 3.18 ± 0.28 g/L; (day 0 and day 70, P = 0.020 and 0.037 respectively), but did not improve insulin resistance (HOMA index and intravenous glucose-tolerance test [ivGGT]) or endothelial function. Despite improvements in inflammatory status, chronic TNF-α neutralization does not improve insulin resistance or endothelial function in seemingly healthy, but obese, insulin-resistant volunteers. This study severely questions the proposal that TNF-α is a causative link between adiposity and insulin resistance.
PMCID: PMC3060990  PMID: 21103669
8.  Multicentric Validation of Proteomic Biomarkers in Urine Specific for Diabetic Nephropathy 
PLoS ONE  2010;5(10):e13421.
Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration ≥5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82).
Methodology/Principal Findings
Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients.
These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin.
PMCID: PMC2958112  PMID: 20975990
9.  Efficacy of a Continuous GLP-1 Infusion Compared With a Structured Insulin Infusion Protocol to Reach Normoglycemia in Nonfasted Type 2 Diabetic Patients: A Clinical Pilot Trial 
Diabetes Care  2009;32(9):1669-1671.
Continuously administered insulin is limited by the need for frequent blood glucose measurements, dose adjustments, and risk of hypoglycemia. Regimens based on glucagon-like peptide 1 (GLP-1) could represent a less complicated treatment alternative. This alternative might be advantageous in hyperglycemic patients hospitalized for acute critical illnesses, who benefit from near normoglycemic control.
In a prospective open randomized crossover trial, we investigated eight clinically stable type 2 diabetic patients during intravenous insulin or GLP-1 regimens to normalize blood glucose after a standardized breakfast.
The time to reach a plasma glucose below 115 mg/dl was significantly shorter during GLP-1 administration (252 ± 51 vs. 321 ± 43 min, P < 0.01). Maximum glycemia (312 ± 51 vs. 254 ± 48 mg/dl, P < 0.01) and glycemia after 2 h (271 ± 51 vs. 168 ± 48 mg/dl, P = 0.012) and after 4 h (155 ± 51 vs. 116 ± 27 mg/dl, P = 0.02) were significantly lower during GLP-1 administration.
GLP-1 infusion is superior to an established insulin infusion regimen with regard to effectiveness and practicability.
PMCID: PMC2732139  PMID: 19528368
10.  Graz Endocrine Causes of Hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism 
Primary aldosteronism (PA) affects approximately 5 to 10% of all patients with arterial hypertension and is associated with an excess rate of cardiovascular complications that can be significantly reduced by a targeted treatment. There exists a general consensus that the aldosterone to renin ratio should be used as a screening tool but valid data about the accuracy of the aldosterone to renin ratio in screening for PA are sparse. In the Graz endocrine causes of hypertension (GECOH) study we aim to prospectively evaluate diagnostic procedures for PA.
Methods and design
In this single center, diagnostic accuracy study we will enrol 400 patients that are routinely referred to our tertiary care center for screening for endocrine hypertension. We will determine the aldosterone to active renin ratio (AARR) as a screening test. In addition, all study participants will have a second determination of the AARR and will undergo a saline infusion test (SIT) as a confirmatory test. PA will be diagnosed in patients with at least one AARR of ≥ 5.7 ng/dL/ng/L (including an aldosterone concentration of ≥ 9 ng/dL) who have an aldosterone level of ≥ 10 ng/dL after the saline infusion test. As a primary outcome we will calculate the receiver operating characteristic curve of the AARR in diagnosing PA. Secondary outcomes include the test characteristics of the saline infusion test involving a comparison with 24 hours urine aldosterone levels and the accuracy of the aldosterone to renin activity ratio in diagnosing PA. In addition we will evaluate whether the use of beta-blockers significantly alters the accuracy of the AARR and we will validate our laboratory methods for aldosterone and renin.
Screening for PA with subsequent targeted treatment is of great potential benefit for hypertensive patients. In the GECOH study we will evaluate a standardised procedure for screening and diagnosing of this disease.
PMCID: PMC2671510  PMID: 19351411

Results 1-10 (10)