D Tschöpe

Ruhr-Universität Bochum, Bochum, North Rhine-Westphalia, Germany

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Publications (206)491.56 Total impact

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    ABSTRACT: Plant-derived α-linolenic acid (ALA) may reduce the risk of CVD, possibly by decreasing systemic inflammation and improving endothelial function. In the present study, the effects of a hypoenergetic diet rich in ALA (3·4 g/d) on the biomarkers of systemic inflammation and vascular function were investigated in eighty-one overweight-to-obese patients with metabolic syndrome traits in comparison with a hypoenergetic diet low in ALA (0·9 g/d, control). After a 6-month dietary intervention, there were significant decreases in the serum concentrations of C-reactive protein (CRP), TNF-α, IL-6, soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial selectin (sE-selectin) and asymmetric dimethylarginine in both dietary groups. However, no inter-group differences were observed for all these changes. The serum concentration of YKL-40 (human cartilage glycoprotein 39 or chitinase-3-like protein 1) decreased after the ALA diet when compared with the control diet (P< 0·05 for time × treatment interaction). Plasma concentrations of fibrinogen did not significantly change in the two dietary groups. The decreases in the serum concentrations of sICAM-1, sE-selectin, CRP and YKL-40 were significantly correlated with the decreases in body fat mass. In conclusion, the present study indicates that in overweight-to-obese patients with metabolic syndrome traits, both vascular function and inflammation are improved during body-weight loss. The high ALA intake led to a more pronounced reduction in the serum concentration of YKL-40 compared with the intake of the low-ALA control diet, indicating the existence of independent favourable physiological effects of ALA during weight loss.
    The British journal of nutrition. 09/2014;
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    ABSTRACT: The genetic polymorphism concerning the Ss3-subunit of platelet integrin receptor glycoprotein IIIa is held responsible for enhanced binding of adhesive proteins resulting in increased thrombogenic potential. Whether it is associated with mortality, HbA1c or platelet volume is tested prospectively in an epidemiological cohort.Research design and methods: Population-based Cooperative Health Research in the Region of Augsburg (KORA) S4-Survey (N = 4,028) was investigated for prognostic value of PLA1A2-polymorphism regarding all-cause mortality, correlation with HbA1c, and mean platelet volume. Multivariate analysis was performed to investigate association between genotype and key variables.
    Cardiovascular Diabetology 05/2014; 13(1):90. · 4.21 Impact Factor
  • D Tschöpe, R Dörr, D Müller-Wieland
    Herz 03/2014; · 0.78 Impact Factor
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    ABSTRACT: Aims We investigated the impact of using an integrated, strip-free system compared to the use of single-strip systems on testing frequency and glycemic control in individuals with insulin-treated diabetes. Methods This multinational, comparative, cluster-randomized, observational study included 311 patients with type 1 and insulin-treated type 2 diabetes who were performing SMBG at suboptimal frequencies. Sites were cluster-randomized to “integrated strip-free” system (EXP group) or any “single-strip” system (CNL group). Testing frequency and HbA1c were measured at baseline, 12 weeks and 24 weeks. Results At week 24, the EXP group showed an increase in SMBG frequency from baseline of 4.17 tests/week (95% CI 2.76, 5.58) compared with an increase of 0.53 tests/week (95% CI –0.73, 1.79) among CNL patients, resulting in a between-group difference of 3.63 tests/week (p<0.0002). Mixed-effects models for repeated measurements (MMRM) controlling for baseline frequency of testing, country and clinical site confirmed a higher SMBG testing frequency in the EXP group compared to the CNL group, with a between-group difference of 2.70 tests/week (p<0.01). Univariate analysis showed greater HbA1c reductions in the EXP group than CNL group: -0.44% (95% CI -0.59, -0.29) vs. -0.13% (95% CI -0.27, 0.01), respectively, p<0.0002. MMRM analyses confirmed these HbA1c reductions. A greater percentage of EXP than CNL patients achieved HbA1c reductions of ≥0.5%: 45.1% vs. 29.1%, respectively, p<0.01. Conclusions The use of an integrated, strip-free SMBG system improved testing adherence and was associated with improvements in glycemic control.
    Journal of Clinical & Translational Endocrinology. 01/2014;
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    ABSTRACT: Recent evidence suggests that omega-3 polyunsaturated fatty acids [n-3 PUFAs: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], improve insulin sensitivity in humans. In a double-blind, placebo-controlled, randomized, crossover study, we investigated the effects of EPA/DHA on paraoxonase-1 activity as well as fasting and postprandial levels of circulating adiponectin and leptin in 34 subjects with type 2 diabetes mellitus who received daily for 6 weeks either 2 g purified EPA/DHA or olive oil (placebo), separated by a 6 weeks washout. At the end of each treatment, measurements were performed in fasting state and 2, 4, and 6 h following a standardized high-fat meal (600 kcal). No significant differences in fasting and postprandial circulating adiponectin, leptin, and paraoxonase-1 activity were seen between n-3 PUFAs and placebo. Our data do not support an insulin sensitizing effect of n-3 PUFAs by means of influencing circulating adipocytokines in this population. Clinical Trial Register Number: NCT00328536.
    Hormone and Metabolic Research 12/2013; · 2.15 Impact Factor
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    ABSTRACT: Methylglyoxal (MG) is a highly reactive dicarbonyl compound derived mainly from glucose degradation pathways, but also from protein and fatty acid metabolism. MG modifies structure and function of different biomolecules and thus plays an important role in the pathogenesis of diabetic complications. Hyperglycemia-associated accumulation of MG might be associated with generation of oxidative stress and subsequently insulin resistance. Therefore, the effects of MG on insulin signaling and on translocation of glucose transporter 4 (GLUT4) were investigated in the rat skeletal muscle cell line L6-GLUT4myc stably expressing myc-tagged GLUT4. Twenty four-hour MG treatment resulted in elevated GLUT4 presentation on the surface of L6 myoblasts and in an increased uptake of glucose even without insulin stimulation. Exogenously added MG neither effected IRS-1 expression nor IRS-1 phosphorylation. A decreased expression of Akt1 but not Akt2 and concomitantly increased apoptosis were detected following MG treatment. To exclude that oxidative stress caused by MG treatment leads to increased GLUT4 translocation, effects of pretreatment with 2 antioxidants were investigated. The antioxidant and MG scavenger NAC prevented the MG-induced GLUT4 translocation. In contrast, tiron, a well-known antioxidant that does not exert MG-scavenger function, had no impact on MG-induced GLUT4 translocation supporting the hypothesis of a direct effect of MG on GLUT4 trafficking. In conclusion, prolonged treatment with MG augments GLUT4 level on the surface of L6 myoblasts, at least in part through a higher translocation of GLUT4 from the intracellular compartment as well as a reduction of GLUT4 internalization, resulting in increased glucose uptake.
    Hormone and Metabolic Research 10/2013; · 2.15 Impact Factor
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    ABSTRACT: DPP-4 inhibitors (DPP4-I) have been shown to provide non-inferior glycaemic control compared with sulfonylureas (SU), but result in a reduction of body weight and a significantly lower risk of hypoglycaemia in patients with type 2 diabetes. We aimed to validate these results in a large real-world sample of patients participating in the prospective DiaRegis registry and to assess prognostic implications. DiaRegis included 3810 patients with type 2 diabetes in which antidiabetic therapy was intensified. We defined two patient subgroups, the first receiving either a DPP4-I or SU on top of prior metformin monotherapy and the second containing patients out of subgroup 1 with unaltered treatment for 1 year. After enrolment 884 patients with prior metformin monotherapy received a dual combination of metformin with either DPP4-I (n = 628; 71%) or SU (n = 256; 29%). Patient characteristics, blood glucose and blood pressure control as well as comorbidity burden were virtually identical. There were neither significant differences in the change of HbA1c over the 12 months treatment period nor in the reduction of body weight, but fasting (p = 0.033) and postprandial glucose levels (p = 0.01) were significantly lower in those receiving DPP4-I. Hypoglycaemia was significantly less frequent in patients receiving DPP4-I (OR 0.32; 95% CI 0.19-0.54). Qualitative changes were robust for subgroup 2 (except of fasting plasma glucose). Patients receiving DPP4-I had significantly less stroke/transitory ischaemic attack (0.2 vs. 2.0; p < 0.05) during the 1 year follow-up, whereas other vascular events (coronary artery bypass graft, percutaneous coronary intervention) were borderline significant. The present results confirm prior randomised controlled trial results in patients with type 2 diabetes from real world clinical practice demonstrating that DPP4-I on top of prior metformin monotherapy result in similar HbA1c reductions within 12 months but a significant reduction in hypoglycaemia compared with sulfonylurea added to metformin. The reduction in vascular events observed has to be verified in larger cohorts.
    International Journal of Clinical Practice 08/2013; · 2.43 Impact Factor
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    ABSTRACT: Abstract Background: Measurements of skin autofluorescence (SAF) allow for a simple and noninvasive quantification of tissue advanced glycation end-products (AGEs), a marker linked to the risk of diabetes complications. The aim of this study was to test the repeatability of SAF over 6 and 12 weeks and to test whether benfotiamine, a thiamine prodrug suggested to reduce AGEs formation under hyperglycemic conditions, is able to attenuate SAF when administered over 6 weeks. Patients and Methods: In a double-blind, placebo-controlled, randomized, crossover study, 22 patients with type 2 diabetes mellitus (T2DM) received 900 mg/day benfotiamine or placebo for 6 weeks (washout period of 6 weeks between). At the beginning and at the end of each treatment period, SAF was assessed in the fasting state, as well as 2, 4, and 6 h following a mixed test meal. Results: The respective intra-individual and inter-individual variability of fasting SAF was 6.9% and 24.5% within 6 weeks and 10.9% and 23.1% within 12 weeks. The respective variability calculated for triplicate comparisons was 9.9% and 27.7%. A short-term therapy with benfotiamine did not influence SAF significantly, nor did we find a significant postprandial SAF increase. Conclusions: In patients with T2DM, repeated, timely spaced SAF measurements have an intra-subject variability of below 11%. Using these data, sample sizes were calculated for interventional studies aiming at reducing SAF. Benfotiamine treatment for 6 weeks did not significantly influence SAF; for this, a longer-term therapy is probably needed.
    Diabetes Technology &amp Therapeutics 08/2013; · 2.21 Impact Factor
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    ABSTRACT: Abstract Background: Prader-Willi syndrome (PWS) is a genetic disorder characterized by morbid obesity resulting from insatiable appetite. Complications like diabetes mellitus or other cardiovascular diseases typically occur during lifetime. Lifestyle advice and education as well as limited caloric intake are the major concepts in assistance of PWS patients. Methods: A 12.9-month follow-up study, which included 8 formerly genetically diagnosed PWS patients, was conducted. Physical and laboratory examinations were done at the beginning and at the end of the follow-up. Improved medical care and lifestyle advice were given. The participants lived in an assisted living environment with a fixed daily schedule and limited caloric intake. Results: The group of patients consisted of manifest diabetics (n=6) as well as nondiabetics (n=2). Therapeutic concepts were simplified in 2 patients by switching from insulin to oral antidiabetics. The reduction in body weight was moderate, but attributable to a loss of fat mass. A significant reduction in blood cholesterol and triglyceride content was achieved along the observational period as well as a significant reduction of glycosylated hemoglobin (HbA1c) in the group of diabetic PWS patients. Systolic blood pressure improved during the study. Conclusion: A combination of an assisted living environment following conservative treatments as well as consistent patient care improved the daily and medical situation of PWS patients. Weight loss and, as a consequence, improvements in terms of metabolic condition and blood pressure were observed. A combination of medical and daily routine management should be established in PWS patients to improve their quality of life.
    Metabolic syndrome and related disorders 07/2013;
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    ABSTRACT: Coronary artery bypass grafting (CABG) is a well-established procedure for treating diabetic patients with multivessel disease, but extracorporeal circulation and cardioplegia-induced cardiac arrest introduce a severe burden to these patients. The present study investigated if off-pump CABG decreases 30-day mortality and mid-term mortality in diabetic patients in comparison with conventional CABG. From February 2009 through October 2011, data from 355 consecutive adult diabetic patients undergoing off-pump CABG and 502 patients undergoing on-pump CABG were prospectively recorded. Data analysis was performed by propensity score (PS)-adjusted logistic regression analysis and PS-adjusted Cox regression analysis. The primary endpoint was 30-day mortality. Secondary endpoints were major complications and mortality on follow-up. Off-pump CABG was associated with a significantly lower 30-day mortality rate (0.3% vs 4.2%; adjusted odds ratio [OR] = 0.09 [95% confidence interval (CI):0.01 to 0.70] p = 0.021) than on-pump CABG. Results coincided with a lower rate of postoperative neurologic complications in patients undergoing off-pump CABG (1.7% vs 5.4%; adjusted OR = 0.31 [95% CI: 0.12 to 0.77] p = 0.012) and a less frequent need for hemofiltration in these patients (3.4% vs 10.4%; adjusted OR = 0.30 [95% CI: 0.14 to 0.64] p = 0.002). The off-pump technique decreased the 6-month mortality rate (2.3% vs 8.8%; adjusted hazard ratio = 0.27 [95% CI: 0.12 to 0.61] p = 0.002) and also the 1-year mortality rate (4.0% vs 10.6%; adjusted hazard ratio = 0.40 [95% CI: 0.22 to 0.75] p = 0.004) significantly. Our data indicate that in terms of postoperative complications and early and mid-term survival, off-pump CABG is superior to the on-pump technique in diabetic patients.
    The Annals of thoracic surgery 06/2013; · 3.45 Impact Factor
  • A Stirban, A Pop, D Tschoepe
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    ABSTRACT: AIMS: In a pilot study we suggested that benfotiamine, a thiamine prodrug, prevents postprandial endothelial dysfunction in people with Type 2 diabetes mellitus. The aim of this study was to test these effects in a larger population. METHODS: In a double-blind, placebo-controlled, randomized, crossover study, 31 people with Type 2 diabetes received 900 mg/day benfotiamine or a placebo for 6 weeks (with a washout period of 6 weeks between). At the end of each treatment period, macrovascular and microvascular function were assessed, together with variables of autonomic nervous function in a fasting state, as well as 2, 4 and 6 h following a heated, mixed test meal. RESULTS: Participants had an impaired baseline flow-mediated dilatation (2.63 ± 2.49%). Compared with the fasting state, neither variable changed postprandially following the placebo treatment. The 6 weeks' treatment with high doses of benfotiamine did not alter this pattern, either in the fasting state or postprandially. Among a subgroup of patients with the highest flow-mediated dilatation, following placebo treatment there was a significant postprandial flow-mediated dilatation decrease, while this effect was attenuated by benfotiamine pretreatment. CONCLUSIONS: In people with Type 2 diabetes and markedly impaired fasting flow-mediated dilatation, a mixed test meal does not further deteriorate flow-mediated dilatation or variables of microvascular or autonomic nervous function. Because no significant deterioration of postprandial flow-mediated dilatation, microvascular or autonomic nervous function tests occurred after placebo treatment, a prevention of the postprandial deterioration of these variables with benfotiamine was not feasible. This article is protected by copyright. All rights reserved.
    Diabetic Medicine 05/2013; · 3.24 Impact Factor
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    ABSTRACT: Metformin is, if not contraindicated and if tolerated, usually preferred over other antidiabetic drugs for the first line treatment of type-2 diabetes. The particular decision on which antidiabetic agent to use is based on variables such as efficacy, cost, potential side effects, effects on weight, comorbidities, hypoglycemia, risk, and patient preferences. However, there is no guidance how to consider these in the selection of antidiabetic drug treatment. In this work, we aimed to summarize available evidence and tried to give pragmatic treatment recommendations from a clinical practice perspective.There are clear contraindications for some drugs in those with impaired renal and liver function and precautions in those with heart failure for the use of metformin (NYHA III-IV) and glitazones. On the other hand, GLP-1 analogs, DPP-4 inhibitors and acarbose are generally less critical and can be used in the majority of patients. We identified the following gaps with respect to the selection of antidiabetic drug treatment in patients with co-morbid disease conditions: 1) Guidelines fail to give advice on the use of specific antidiabetic drugs in patients with co-morbidity. 2) The literature is deficient in studies documenting antidiabetic drug use in patients with severely impaired renal function, diabetic retinopathy, cerebrovascular disease and systolic heart failure. 3) Further there are no specific data on patients with multiple of these co-morbid disease conditions. We postulate that differential use of antidiabetic drugs in patients with co-morbid disease constellations will help to reduce treatment related complications and might improve prognosis.
    Cardiovascular Diabetology 04/2013; 12(1):62. · 4.21 Impact Factor
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    ABSTRACT: BACKGROUND: Type-2 diabetes mellitus has a major impact on health related quality of life (HRQoL). We aimed to identify patient and treatment related variables having a major impact. METHODS: DiaRegis is a prospective diabetes registry. The EQ-5D was used to describe differences in HRQoL at baseline. Odds ratios (OR) with 95% confidence intervals (CI) were determined from univariable regression analysis. For the identification of independent predictors of a low score on the EQ-5D, multivariable unconditional logistic regression analysis was performed. RESULTS: A total of 2,760 patients were available for the present analysis (46.7% female, median age 66.2 years). Patients had considerable co-morbidity (18.3% coronary artery disease, 10.6% heart failure, 5.9% PAD and 5.0% stroke/TIA). Baseline HbA1c was 7.4%, fasting- and postprandial plasma glucose 139 mg/dl and 183 mg/dl.The median EQ-5D was 0.9 (interquartile range [IQR] 0.8--1.0). Independent predictors for a low EQ-5D were age > 66 years (OR 1.49; 95%CI 1.08--2.06), female gender (2.11; 1.55--2.86), hypertension (1.73; 1.03--2.93), peripheral neuropathy (1.62; 0.93--2.84) and clinically relevant depression (11.01; 3.97--30.50). There was no influence of dysglycaemia on the EQ-5D score. CONCLUSION: The present study suggests, that co-morbidity but not average glycaemic control reduces health related quality of life in type 2 diabetes mellitus.
    Cardiovascular Diabetology 03/2013; 12(1):47. · 4.21 Impact Factor
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    ABSTRACT: Methylglyoxal (MG), a highly reactive α-dicarbonyl metabolite of glucose degradation pathways, protein and fatty acid metabolism, plays an important role in the pathogenesis of diabetic complications. Hyperglycemia triggers enhanced production of MG and increased generation of advanced glycation endproducts (AGEs). In non-enzymatic reactions, MG reacts with arginine residues of proteins to form the AGEs argpyrimidine and hydroimidazolone. Glyoxalase 1 (GLO1), in combination with glyoxalase 2 and the co-factor glutathione constitute the glyoxalase system, which is responsible for the detoxification of MG. A GLO1 specific knock down results in accumulation of MG in targeted cells. The aim of this study was to investigate the effect of intracellularly accumulated MG on insulin signaling and on the translocation of the glucose transporter 4 (GLUT4). Therefore, L6 cells stably expressing a myc-tagged GLUT4 were examined. For the intracellular accumulation of MG, GLO1, the first enzyme of the glyoxalase pathway, was down regulated by siRNA knock down and cells were cultivated under hyperglycemic conditions (25 mM glucose) for 48 h. Here we show that GLO1 knock down augmented GLUT4 level on the cell surface of L6 myoblasts at least in part through reduction of GLUT4 internalization, resulting in increased glucose uptake. However, intracellular accumulation of MG had no effect on GLUT4 concentration or modification. The antioxidant and MG scavenger NAC prevented the MG-induced GLUT4 translocation. Tiron, which is also a well-known antioxidant, had no impact on MG-induced GLUT4 translocation.
    PLoS ONE 01/2013; 8(5):e65195. · 3.53 Impact Factor
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    ABSTRACT: OBJECTIVES Recent evidence indicates that heat-enhanced food advanced glycation end products (AGEs) adversely affect vascular function. The aim of this study was to examine the acute effects of an oral load of heat-treated, AGE-modified β-lactoglobulins (AGE-BLG) compared with heat-treated, nonglycated BLG (C-BLG) on vascular function in patients with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODS In a double-blind, controlled, randomized, crossover study, 19 patients with T2DM received, on two different occasions, beverages containing either AGE-BLG or C-BLG. We measured macrovascular [brachial ultrasound of flow-mediated dilatation (FMD)] and microvascular (laser-Doppler measurements of reactive hyperemia in the hand) functions at baseline (T(0)), 90 (T(90)), and 180 (T(180)) min.RESULTSFollowing the AGE-BLG, FMD decreased at T(90) by 80% from baseline and remained decreased by 42% at T(180) (P < 0.05 vs. baseline, P < 0.05 vs. C-BLG at T90). By comparison, following C-BLG, FMD decreased by 27% at T(90) and 51% at T(180) (P < 0.05 vs. baseline at T180). A significant decrease in nitrite (T(180)) and nitrate (T(90) and T(180)), as well as a significant increase in N(ε)-carboxymethyllisine, accompanied intake of AGE-BLG. There was no change in microvascular function caused by either beverage.CONCLUSIONS In patients with T2DM, acute oral administration of a single AGE-modified protein class significantly though transiently impaired macrovascular function in concert with decreased nitric oxide bioavailability. These AGE-related changes were independent of heat treatment.
    Diabetes care 12/2012; · 7.74 Impact Factor
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    ABSTRACT: BACKGROUND: Patients with type 2 diabetes have 2--4 times greater risk for cardiovascular morbidity and mortality than those without, and this is even further aggravated if they also suffer from hypertension. Unfortunately, less than one third of hypertensive diabetic patients meet blood pressure targets, and more than half fail to achieve target HbA1c values. Thus, appropriate blood pressure and glucose control are of utmost importance. Since treatment sometimes fails in clinical practice while clinical trials generally suggest good efficacy, data from daily clinical practice, especially with regard to the use of newly developed anti-diabetic and anti-hypertensive compounds in unselected patient populations, are essential. The DIALOGUE registry aims to close this important gap by evaluating different treatment approaches in hypertensive type 2 diabetic patients with respect to their effectiveness and tolerability and their impact on outcomes. In addition, DIALOGUE is the first registry to determine treatment success based on the new individualized treatment targets recommended by the ADA and the EASD. METHODS: DIALOGUE is a prospective observational German multicentre registry and will enrol 10,000 patients with both diabetes and hypertension in up to 700 sites. After a baseline visit, further documentations are scheduled at 6, 12 and 24 months. There are two co-primary objectives referring to the most recent guidelines for the treatment of diabetes and hypertension: 1) individual HbA1c goal achievement with respect to anti-diabetic pharmacotherapy and 2) individual blood pressure goal achievement with different antihypertensive treatments. Among the secondary objectives the rate of major cardio-vascular and cerebro-vascular events (MACCE) and the rate of hospitalizations are the most important. CONCLUSION: The registry will be able to gain insights into the reasons for the obvious gap between the demonstrated efficacy and safety of anti-diabetic and anti-hypertensive drugs in clinical trials and their real world balance of effectiveness and safety.
    Cardiovascular Diabetology 12/2012; 11(1):148. · 4.21 Impact Factor
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    ABSTRACT: BACKGROUND: Hypoglycaemia is a serious adverse effect of antidiabetic drug therapy. We aimed to determine incidence rates of hypoglycaemia in type-2 diabetic patients and identify predictors of hypoglycaemia when treatment is intensified. METHODS: DiaRegis is a prospective German registry that follows 3810 patients with type-2 diabetes referred for treatment intensification because of insufficient glycaemic control on one or two oral antidiabetic drugs. RESULTS: Out of a total of 3347 patients with data available for the present analysis 473 (14.1%) presented any severity hypoglycaemia over a follow-up of 12 months. 0.4% were hospitalized (mean of 1.3+/-0.6 episodes), 0.1% needed medical assistance (1.0+/-0.0), 0.8% needed any help (1.1+/-0.5) and 10.1% no help (3.4+/-3.7), and 8.0% had no specific symptoms (3.6+/-3.5). Patients with incident hypoglycaemia had longer diabetes duration, higher HbA1c and a more frequent smoking history; more had co-morbid disease conditions such as coronary artery disease, peripheral arterial disease, amputation, heart failure, peripheral neuropathy, diabetic retinopathy and clinically relevant depression at baseline. Multivariable adjusted positive predictors of incident hypoglycaemia over the follow-up were prior anamnestic hypoglycaemia, retinopathy, depression, insulin use and blood glucose self-measurement, but not sulfonylurea use as previously reported for anamnestic or recalled hypogylcaemia. On the contrary, glitazones, DPP-4 inhibitors and GLP-1 analogues were associated with a reduced risk of hypoglycaemia. CONCLUSIONS: Hypoglycaemia is a frequent adverse effect in ambulatory patients when antidiabetic treatment is intensified. Particular attention is warranted in patients with prior episodes of hypoglycaemia, microvascular disease such as retinopathy and in patients receiving insulin. On the other hand glitazones, DPP-4 inhibitors and GLP-1 analogues are associated with a reduced risk.
    BMC Endocrine Disorders 10/2012; 12(1):23. · 2.65 Impact Factor
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    ABSTRACT: BACKGROUND: We aimed at identifying variables predicting hypoglycemia in elderly type 2 diabetic patients and the relation to HbA1c values achieved. DESIGN: Prospective, observational registry in 3810 patients in primary care. Comparison of patients in different age tertiles: with an age < 60 (young, n=1,253), age 60 to < 70 (middle aged, n=1,184) to those >= 70 years (elderly, n=1,373). Odds Ratios (OR) with 95% confidence intervals (CI) were determined from univariable and multivariable regression analyses. RESULTS: Elderly patients had a later diabetes diagnosis, a longer diabetes duration, better glucose control and more frequent co-morbid disease conditions. Overall 10.7% of patients experienced any severity hypoglycemia within the last 12 months prior to inclusion. Higher rates of hypoglycemia were observed in the elderly than in the young after adjusting for differences in HbA1c, fasting and post-prandial blood glucose (OR 1.68; 95%CI 1.16-2.45). This was particularly true for hypoglycemic episodes without specific symptoms (OR 1.74; 95%CI 1.05-2.89). In a multivariate model stroke / transitory ischemic attack, the presence of heart failure, clinically relevant depression, sulfonylurea use and blood glucose self-measurement were associated with hypoglycemic events. CONCLUSION: Elderly patients are at an increased risk of hypoglycemia even at comparable glycemic control. Therefore identified variables associated with hypoglycemia in the elderly such as heart failure, clinically relevant depression, the use of sulfonylurea help to optimize the balance between glucose control and low levels of hypoglycemia. Asymptomatic hypoglycemia should not be disregarded as irrelevant but considered as a sign of possible hypoglycemia associated autonomic failure.
    Cardiovascular Diabetology 10/2012; 11(1):122. · 4.21 Impact Factor
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    ABSTRACT: AIMS: Patients with type 2 diabetes are at high risk for developing heart failure. Evidence-based treatment recommendations with respect to the specific benefits or possible hazards of antidiabetic treatment are scarce. METHODS AND RESULTS: In a systematic search we only identified randomized, controlled trials for thiazolidinediones. Further evidence is largely based on subgroup analyses of larger intervention studies in mostly systolic heart failure, on observational studies, or on registries. Acknowledging this lack of data, hyperglycaemia should be treated to appropriate guideline-recommended targets and hypoglycaemia avoided until this evidence becomes available. Thiazolidinediones should not be used because of an increased event rate in diabetic patients with established heart failure and a large increase in incident heart failure. All other glucose-lowering strategies might be used in patients with diabetes and heart failure, but specific precautions must be considered. CONCLUSIONS: The documented lack of data calls for specific trials, as diabetes and heart failure as well as their co-morbidities are highly prevalent and are becoming even more important with an increasing prevalence of obesity and an ageing population.
    European Journal of Heart Failure 09/2012; · 5.25 Impact Factor
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    ABSTRACT: Possible fatal complications of human insulin and its synthetic analogues like hypoglycemia require precise classification and quantitative determination of these drugs both for clinical purposes as well as for forensic toxicologists. A procedure was developed for the identification and quantification of human insulin and different long-acting as well as short-acting synthetic insulins in human blood serum specimens. After an immunoaffinity purification step and separation by liquid chromatography, the insulins were characterized by their five- or sixfold protonated molecule ions and diagnostic product ions. Clinical samples of 207 diabetic and 50 non-diabetic patients after the administration of human insulin or oral antidiabetics and forensic samples were analyzed for human/synthetic insulin concentrations. The method was validated according to international guidelines. Limits of detection of the insulins ranged between 1.3 and 2.8 μU/ml. Recoveries ranged between 33.2 % and 51.7 %. Precision data was in accordance with international guidelines. Clinical samples showed concentrations of human insulin lower than 301 μU/ml. Our liquid chromatography tandem mass spectrometry procedure allows unambiguous identification and quantification of the intact human insulin and its intact synthetic analogues Humalog®, Novolog®, Apidra®, Lantus®, and Levemir® in human blood serum in clinical and overdose cases. The assay could be successfully tested in patients with diabetes mellitus on therapy with insulins or oral antidiabetics.
    Analytical and Bioanalytical Chemistry 08/2012; 404(6-7):1813-22. · 3.66 Impact Factor

Publication Stats

2k Citations
491.56 Total Impact Points

Institutions

  • 2004–2014
    • Ruhr-Universität Bochum
      • Institut für Klinische Chemie, Transfusions- und Laboratoriumsmedizin
      Bochum, North Rhine-Westphalia, Germany
    • MediClin
      Essen, North Rhine-Westphalia, Germany
    • University of California, San Diego
      • Division of Epidemiology
      San Diego, CA, United States
  • 2013
    • Institut für Herzinfarktforschung
      Mayence, Rheinland-Pfalz, Germany
  • 2012–2013
    • Krankenhaus Bad Oeynhausen
      Bad Oeyhausen, North Rhine-Westphalia, Germany
    • University of Bonn
      Bonn, North Rhine-Westphalia, Germany
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2004–2013
    • Herz- und Diabeteszentrum Nordrhein-Westfalen
      • Heart Center North Rhine-Westphalia
      Bad Oeyhausen, North Rhine-Westphalia, Germany
  • 2011–2012
    • Praxisklinik Herz Und Gefässe
      Dresden, Saxony, Germany
    • Klinikum Ludwigshafen
      • Medizinische Klinik A
      Ludwigshafen, Rheinland-Pfalz, Germany
  • 2008
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
  • 1988–2006
    • Heinrich-Heine-Universität Düsseldorf
      • Brain Research Institute
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1998–1999
    • Freie Universität Berlin
      Berlín, Berlin, Germany
  • 1994
    • German Diabetes Center
      Düsseldorf, North Rhine-Westphalia, Germany