Mark Lankisch

Subclinical inflammation and diabetic polyneuropathy: MONICA/KORA Survey F3 (Augsburg, Germany).

OBJECTIVE Subclinical inflammation represents a risk factor of type 2 diabetes and several diabetes complications, but data on diabetic neuropathies are scarce. Therefore, we investigated whether circulating concentrations of acute-phase proteins, cytokines, and chemokines differ among diabetic patients with or without diabetic polyneuropathy. RESEARCH DESIGN AND METHODS We measured 10 markers of subclinical inflammation in 227 type 2 diabetic patients with diabetic polyneuropathy who participated in the population-based MONICA/KORA Survey F3 (2004–2005; Augsburg, Germany). Diabetic polyneuropathy was diagnosed using the Michigan Neuropathy Screening Instrument (MNSI). RESULTS After adjustment for multiple confounders, high levels of C-reactive protein and interleukin (IL)-6 were most consistently associated with diabetic polyneuropathy, high MNSI score, and specific neuropathic deficits, whereas some inverse associations were seen for IL-18. CONCLUSIONS This study shows that subclinical inflammation is associated with diabetic polyneuropathy and neuropathic impairments. This association appears rather specific because only certain immune mediators and impairments are involved.

Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders.

BackgroundDiabetes mellitus (DM) has reached epidemic proportions and is an important risk factor for heart failure (HF). Left ventricular diastolic dysfunction (LVDD) is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels (TNF-alpha, IL-6) and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease.MethodsWe enrolled 41 consecutive patients (mean age 65+/-10 years) submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E) transmitral flow velocity was measured. LVDD was defined as E/Em ratio ≥ 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes.ResultsPatients with E/Em ratio ≥ 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline) had significantly higher IL-6 (P = 0,001), TNF-alpha (P < 0,001) and NT-pro- BNP (P = 0,001) plasma levels compared to those with normal diastolic function. TNF-alpha and IL-6 levels remains significantly elevated after adjustment for sex, age, left ventricular ejection function, body mass index, coronary heart disease, smoking, hypertension and diabetes mellitus with linear regression analysis. Furthermore, in subjects LVDD or borderline LV diastolic function, 75% had diabetes or IGT, respectively. When subjects without diabetes were excluded, both IL-6 (P = 0,006) and TNF-alpha (P = 0,002) remained significantly elevated in subjects with E/Em ratio ≥ 15.ConclusionThis study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction.

Effect of the Frequency of Self-Monitoring Blood Glucose in Patients with Type 2 Diabetes Treated with Oral Antidiabetic Drugs—A Multi-Centre, Randomized Controlled Trial

Objective Recommendations on the frequency of self-monitoring of blood glucose (SMBG) vary widely among physicians treating patients with type 2 diabetes (T2D). Aim of this study was to investigate two testing regimen of SMBG in patients with stable metabolic control. Research Design and Methods Patients with T2D treated with oral antidiabetic drugs were randomized to two groups: either one SMBG (low) or four SMBG (high) per week. Subjects were followed up after 3, 6 and 12 months. Primary outcome parameter was the change in HbA1c between baseline and 6 months. Primary outcome criterion was tested by a one-sided t- test for non- inferiority. Secondary outcome parameters were safety, compliance and HbA1c at 3 and 12 months. Results There were no differences in the 202 subjects for demographic and sociodemographic parameters and drug treatment. HbA1c (%) at baseline was similar in both groups (7.2±1.4 vs. 7.2±1.0). Non- inferiority was demonstrated for the low group (p = 0.0022) with a difference from baseline to 6 months of 0.24 in the low and of 0.16 in the high group. Compliance with the testing regimen was 82–90% in both groups. There were no statistical significant differences for compliance, HbA1c at 3 and 12 months and serious adverse events (SAE). Conclusion One SMBG per week is as sufficient and safe as four SMBG per week to maintain HbA1c in non-insulin treated T2D close to metabolic target. The results of this study are in contrast to current international consensus guidelines. Trial Registration Controlled-Trials.com ISRCTN79164268

Screening for undiagnosed diabetes in patients with acute myocardial infarction

BackgroundScreening for undiagnosed diabetes in patients with acute myocardial infarction is recommended (ESC and EASD Task Force 2007). Glucose tolerance testing in the peri-infarct period may not be valid because of confounding, e.g. by the acute stress reaction. The aim was to evaluate undiagnosed diabetes (DM) and impaired glucose regulation (IGR) in AMI during hospital stay and 3 months after discharge.Materials and methodsIn 96 consecutively admitted AMI patients (Heart Center Wuppertal, Germany) OGTT were performed, of whom in 62 OGTT were also carried out 3 months later.ResultsBefore discharge 32% of the patients had newly diagnosed diabetes and 47% patients had prediabetes (IGR). Glucose tolerance was normal in 20 (21%) patients only. After 3 months, 74% with newly diagnosed DM at baseline still had disturbed glucose metabolism (58% DM, 16% IGT). No patient with normal OGTT became diabetic after 3 months. In multivariate regression, the odds of having diabetes (3 months) was about sixfold higher when having diabetes before discharge (OGTT). Admission glucose, infarction size CKMAX, and inflammation (CRP) were not significantly related to OGTT results.ConclusionsThis prospective study confirms a high prevalence of undiagnosed DM in patients with AMI. In about 60% of AMI patients, newly diagnosed DM persisted after 3 months. For the first time we could show that there is no correlation between infarction size and undiagnosed diabetes. Thus, an OGTT performed before discharge may provide a reliable measure of disturbed glucose regulation but needs to be repeated.

Reduced global longitudinal strain in association to increased left ventricular mass in patients with aortic valve stenosis and normal ejection fraction: a hybrid study combining echocardiography and magnetic resonance imaging

BackgroundIncreased muscle mass index of the left ventricle (LVMi) is an independent predictor for the development of symptoms in patients with asymptomatic aortic stenosis (AS). While the onset of clinical symptoms and left ventricular systolic dysfunction determines a poor prognosis, the standard echocardiographic evaluation of LV dysfunction, only based on measurements of the LV ejection fraction (EF), may be insufficient for an early assessment of imminent heart failure. Contrary, 2-dimensional speckle tracking (2DS) seems to be superior in detecting subtle changes in myocardial function. The aim of the study was to assess these LV function deteriorations with global longitudinal strain (GLS) analysis and the relations to LVMi in patients with AS and normal EF.Methods50 patients with moderate to severe AS and 31 controls were enrolled. All patients underwent echocardiography, including 2DS imaging. LVMi measures were performed with magnetic resonance imaging in 38 patients with AS and indexed for body surface area.ResultsThe total group of patients with AST showed a GLS of -15,2 ± 3,6% while the control group reached -19,5 ± 2,7% (p < 0,001). By splitting the group with AS in normal, moderate and severe increased LVMi, the GLS was -17,0 ± 2,6%, -13,2 ± 3,8% and -12,4 ± 2,9%, respectively (p = 0,001), where LVMi and GLS showed a significant correlation (r = 0,6, p < 0,001).ConclusionsIn conclusion, increased LVMi is reflected in abnormalities of GLS and the proportion of GLS impairment depends on the extent of LV hypertrophy. Therefore, simultaneous measurement of LVMi and GLS might be useful to identify patients at high risk for transition into heart failure who would benefit from aortic valve replacement irrespectively of LV EF.

High prevalence of undiagnosed impaired glucose regulation and diabetes mellitus in patients scheduled for an elective coronary angiography

SummaryBackgroundImpaired glucose regulation (IGR) and diabetes mellitus (DM) are amongst the main risk factors for developing coronary heart disease (CHD). The aim of this study was to investigate previously unknown glucose metabolism disorder in patients scheduled for an elective coronary angiography.MethodsA total of 141 patients scheduled for coronary angiography without signs of acute myocardial ischemia or previous history of a glucose metabolism disorder were prospectively included in the study. An oral glucose tolerance test (OGTT) was performed in each patient.ResultsIGR was diagnosed in 40.4% (95% confidence interval 32.3–49.0) and undetected DM in 22.7% (16.1–30.5) of patients undergoing an elective coronary angiography. Depending on the severity of CHD, the percentage of IGR and DM increased up to 45.3% (34.6–56.5) and 26.7% (17.8–37.4) in the subgroup with the need of percutaneous angioplasty, while the corresponding proportions in the group without CHD were 30.3% (15.6–48.7) and 12.1% (3.4–28.2). The percentage of undiagnosed DM increased with the number of epicardial vessels involved. Using the recommended fasting plasma glucose value of ≥ 126 mg/dl for the diagnosis of DM, we would have missed 71.9% of the patients with undiagnosed DM.If all patients with a fasting plasma glucose of ≥ 90 mg/dl had been subjected to OGTT, 93.8% of DM would have been identified.ConclusionsPrevalences of DM and IGR are higher than expected in patients with CHD. An OGTT should be considered for all patients with a fasting plasma glucose ≥ 90 mg/dl undergoing a coronary angiography.

Metabolic syndrome with or without diabetes contributes to left ventricular diastolic dysfunction

Objective Left ventricular diastolic dysfunction (LVDD) is considered a precursor of diabetic cardiomyopathy, while the metabolic syndrome (MetS) is associated with an increased risk of cardiovascular morbidity and mortality. This study aimed to evaluate the association between LVDD, MetS and glucose metabolism disturbances classifi ed by oral glucose tolerance testing (oGTT). Methods and results The presence of LVDD was evaluated in 166 subjects with normal ejection fraction, 43 (26%) of whom had type 2 diabetes at inclusion. In subjects without diabetes, an oGTT was performed. The MetS was diagnosed as indentifi ed by the NCEPIII-criteria, while LVDD was verifi ed and graded according to the current guidelines. MetS was diagnosed in 97 (59%) patients, 44% of whom had known diabetes. The prevalence of LVDD was 68% in subjects with MetS vs. 19% in patients without MetS, respectively (P < 0.001). A severe form of LVDD was observed in 34% and 15% of patients with and without MetS, respectively (P= 0.001), whereupon the prevalence of mild and severe diastolic dysfunction increased with the number of MetS criteria (P= 0.001). In the MetS group, early diastolic tissue relaxation velocity (E´) was signifi cantly reduced (6.9 ± 1.8 cm/s vs. 7.7 ± 2.1 cm/s; P= 0.009) and the E/E´ ratio was signifi cantly higher (10.5 ± 3.9 vs. 9.1 ± 3.0 cm/s, P= 0.015) as compared to the group without MetS (n = 69). Conclusion MetS was associated with a higher prevalence and severity of LVDD, whereupon coexisting diabetes aggravates these fi nding. Patients displaying MetS with concomitant LVDD might represent a target population in which appropriate medical care for early heart failure prevention should be initiated

Limiting esophageal temperature in radiofrequency ablation of left atrial tachyarrhythmias results in low incidence of thermal esophageal lesions

BackgroundAtrio-esophageal fistula formation following radiofrequency ablation of left atrial tachyarrhythmias is a rare but devastating complication. Esophageal injuries are believed to be precursors of fistula formation and reported to occur in up to 47% of patients. This study investigates the incidence of esophageal lesions when real time esophageal temperature monitoring and temperature limitation is used.Methods184 consecutive patients underwent open irrigated radiofrequency ablation of left atrial tachyarrhythmias. An esophageal temperature probe consisting of three independent thermocouples was used for temperature monitoring. A temperature limit of 40°C was defined to interrupt energy delivery. All patients underwent esophageal endoscopy the next day.ResultsEndoscopy revealed ulcer formation in 3/184 patients (1.6%). No patient developed atrio-esophageal fistula. Patient and disease characteristics had no influence on ulcer formation. The temperature threshold of 40°C was reached in 157/184 patients. A temperature overshoot after cessation of energy delivery was observed frequently. The mean maximal temperature was 40.8°C. Using a multiple regression analysis creating a box lesion that implies superior- and inferior lines at the posterior wall connecting the right and left encircling was an independent predictor of temperature. Six month follow-up showed an overall success rate of 78% documented as sinus rhythm in seven-day holter ECG.ConclusionLimitation of esophageal temperature to 40°C is associated with the lowest incidence of esophageal lesion formation published so far. This approach may contribute to increase the safety profile of radiofrequency ablation in the left atrium.

Gender-based differences in long-term outcome after ST-elevation myocardial infarction in patients treated with percutaneous coronary intervention.

BACKGROUND In the era of fibrinolysis, women suffered from higher early and late mortality rates than men after acute ST-elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) has been determined to be the most effective therapy strategy in STEMI. It is not clear if female gender is an independent predictor of a worse long-term prognosis among patients who were systematically treated with PCI. We, therefore, examined the effect of PCI on long-term outcome between women and men. METHODS Between 1999 and 2001, 500 consecutive patients at the Wuppertal Heart Centre were treated with PCI after acute STEMI. A long-term follow-up (up to 7 years) was achieved in 97% of the patients. RESULTS In comparison to men, women were 7 years older (65 +/- 12 vs. 58 +/- 11) and had significantly more diabetes mellitus. The time between onset of symptoms and intervention tended to be longer in women than men. There was no difference in 30-day mortality (8.9% vs. 6.6%), cardiac late mortality (3.6% vs. 3.2%), and long-term cardiac overall mortality up to 7 years (12.1% vs. 9.6%). Stepwise regression analysis did not identify female gender as an independent predictor of late mortality. The quality of life was comparable. CONCLUSIONS There was no gender-related difference in the long-term outcome if patients were sytematically treated with PCI in STEMI. PCI in STEMI has a long-lasting positive effect in women and should, therefore, be considered the treatment of choice for women with acute myocardial infarction.

Increased levels of laminin and collagen type VI may reflect early remodelling in patients with acute myocardial infarction.

Objective — The development of left ventricular remodelling (LVR) after acute myocardial infarction (AMI) is a predictor of heart failure and mortality.The extracellular matrix (ECM) is highly susceptible to ischaemic injury. Laminin and collagen type VI (CVI) contribute to ECM formation in the infarct zone.To determine whether these markers can be detected in blood samples, we measured laminin and CVI in patients with AMI and control subjects. Methods — A total of 60patients scheduled for coronary angiography and 31patients with AMI were included.We subdivided the patients into three groups: (1) AMI, (2) stable coronary artery disease (CAD) and (3) exclusion of CAD. Laminin and CVI serum concentrations were recorded using the ELISA-technique. Results — Laminin was significantly higher in patients with AMI than in subjects with stable CAD (36.5 vs. 23.9, P<0.01) or without CAD (36.5 vs. 24.6ng/ml, P<0.05). CVI-levels were significantly elevated in patients with AMI compared to subjects without CAD (7.5ng/ml vs. 5.4ng/ml, P<0.05) or stable CAD (7.5ng/ml vs. 5.7ng/ml, P=0.01). Laminin and CVI were significantly higher in patients with severely reduced left ventricular function. Laminin and CVI values were significantly correlated (r=0.6). Conclusion — Our data suggest that laminin and CVI serum levels can be potential surrogate parameters of ECM remodelling after AMI.We hypothesize that serum laminin reflects early ECMremodelling involved in the process of postischaemic tissue degradation and repair, and CVI may be a marker of collagen denaturation and shifts in the collagen phenotype ratios.