Cardiovascular outcome in type 2 diabetes and atrial fibrillation.

Diabetes is an independent risk factor for atrial fibrillation (AF). Frequently, it is part of the metabolic syndrome cluster, which includes obesity and hypertension that are independently associated with AF. The risk appears to be higher with longer duration of diabetes and inadequate glycemic control. Patients with diabetes and AF have a substantially increased risk of death and serious cardiovascular complications compared with those in sinus rhythm. Conversely, good metabolic control appears to be associated with maintenance of rhythm after successful therapeutic conversion to sinus rhythm by catheter ablation or electrical cardioconversion of AF. AF puts patients with type 2 diabetes at a high risk of cardiovascular complications and death, which could be successfully addressed by new classes of antidiabetic agents such as incretin analogues or sglt-2 inhibitors. Thus, a diagnostic strategy that addresses the increased risk for AF is urgently recommended, in addition to diabetes monitoring in routine outpatient practice. In order to prevent thromboembolic complications, which frequently determine the prognosis for this patient population, appropriate anticoagulation remains the mainstay of therapy, whereas the prognostic value of reinstalling sinus rhythm awaits further evidence.

Impact of body weight on antidiabetic treatment and predictors of weight control under real-world conditions: a 2-year follow-up of DiaRegis cohort.

AIMS: Treatment strategies for obese patients with type 2 diabetes mellitus aim to increase physical activity, reduce body weight, and improve glucose control using weight-beneficial antidiabetic drugs. The objective of this study was to determine whether these strategies are implemented, and to identify factors predictive of glucose control and body weight management in a large, real-world patient population. METHODS: The prospective DiaRegis cohort study included 3807 patients with type 2 diabetes in whom the treating physician decided to intensify and optimize treatment because of insufficient glucose control. RESULTS: Antidiabetic treatment of overweight and obese patients was compared with that of normal-weight patients over a 2-years follow-up period, and multivariate analyses were performed to identify predictors of body weight loss. Among the 3807 participants, 92.5 % were overweight or obese. Normal-weight participants were more often treated with sulfonylureas or insulin, and overweight and obese patients with metformin or glucagon-like peptide (GLP)-1 analogues. Predictors of weight loss were body mass index (BMI) ≥30 kg/m(2) and any reported physical activity. CONCLUSIONS: DiaRegis study shows that under real-world conditions, antidiabetic drug therapy is performed dependent on body weight. This strategy results in adequate glucose control and moderate weight reductions in overweight and obese patients. Weight loss is affected by treatment with weight-beneficial drugs, but also by any reported physical activity. However, only a small subgroup of patients perform physical activity. Initiation and maintenance of a physically active lifestyle remains a significant challenge for physicians, and patients with type 2 diabetes.

Prognostic implications of DPP-4 inhibitor vs. sulfonylurea use on top of metformin in a real world setting - results of the 1 year follow-up of the prospective DiaRegis registry.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Comorbidity, hypoglycaemia and appropriate selection of antidiabetic pharmacotherapy in diabetic patients with heart failure in clinical practice in Germany. Results of the DiaRegis registry].

BACKGROUND: Patients with type 2 diabetes and heart failure are considered to be at high risk for hypoglycaemic complications. There is a considerable uncertainty with respect to the appropriate choice of antidiabetic pharmacotherapy in patients with type 2 diabetes and comorbid heart failure. Little is known about comorbidity, hypoglycaemia rates and selected pharmacotherapy in diabetic patients with heart failure in clinical practice. METHODS: DiaRegis is a prospective registry in Germany including 3,810 patients with type 2 diabetes receiving antidiabetic treatment with oral mono or oral dual combination therapy in 2009/2010. Only patients for which adjustment of pharmacotherapy (including the introduction of insulin and GLP-1 analogues) was deemed necessary were enrolled. We examined the differences in comorbidity, hypoglycaemia and choice of anti-diabetic pharmacotherapy between diabetics with and without clinical heart failure in clinical practice in Germany. RESULTS: For 3,746 patients, data on the presence of heart failure were available, median (IQR) age 65.9 (57.6-72.8) years and 46.8% were female. Patients with heart failure (n = 370; 9.9%) were older, had a higher BMI, were less physically active, and had more cardiovascular risk factors and a substantial comorbidity. Glycaemic control was comparable between groups. Of the patients with heart failure, 76.8% received metformin, 32.7% sulfonylureas, 2.2% glucosidase inhibitors, 4.3% glinides, 6.2% glitazones and 7.3% DPP-4 inhibitors at baseline before adjustment of therapy. In multivariate analyses, patients with heart failure received less metformin (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.43-0.79) and sulfonylureas (OR 0.70, 95%CI 0.52-0.95) but not thiazolidinediones (OR 1.22, 95%CI 0.82-1.81) or other antidiabetic drugs. Hypoglycaemia was considerably more frequent in diabetic patients with heart failure than in those without (OR 1.96, 95%CI 1.47-2.61). CONCLUSION: Patients with type 2 diabetes and heart failure had a substantially increased comorbidity burden compared to patients without heart failure. They more often suffered from episodes of hypoglycaemia, especially those requiring medical assistance. The diagnosis of heart failure did not impact the choice of antidiabetic pharmacotherapy in patients with type 2 diabetes. There was no differential use of thiazolidinediones despite evidence discouraging their use in patients with heart failure.

[Prevalence of undetected diabetes mellitus in invasive and interventional cardiology. Silent diabetes in the catheterization laboratory]. / Prävalenz unentdeckter Glukosestoffwechselstörungen in der invasiven und interventionellen Kardiologie. "Silent diabetes" im Herzkatheterlabor.

In most randomized controlled trials on revascularization therapy for patients with ischemic coronary artery disease (CAD), the diabetes prevalence ranges between 15% and 35%. However, the true prevalence of diabetes is probably considerably underestimated in these trials. The European heart survey diabetes and the heart published in 2004 supplied strong evidence that there are many additional cases of undetected prediabetics and diabetics in any cardiology patient cohort. The long-term outcome of newly detected diabetics was found to be comparable to patients with already known diabetes mellitus. With this in mind, the Dresden silent diabetes study investigated the prevalence of undetected diabetes mellitus by oral glucose tolerance testing (OGTT) and comparative HbA1c sampling in 1,015 patients admitted for coronary angiography. Patients with known diabetes were excluded from the study.According to the OGTT only 513 patients (51%) were classified with normal glucose tolerance (NGT), 10 (1%) with isolated impaired fasting glucose (IFG), 349 (34%) with impaired glucose tolerance (IGT) and 143 (14%) were diagnosed with newly detected diabetes mellitus (DM). According to the HbA1c measurements 588 patients (58%) were classified as normal, 385 (38%) as borderline and only 42 (4%) were diagnosed with diabetes (DM). There was a significant correlation between the extent of CAD and glycemic status as defined by the OGTT. The number of patients with IGT and diabetes increased with the extent of CAD (IGT group p<0.001, diabetes group p=0.01). However, no such correlation was observed when glycemic status was defined by HbA1c testing.Based on these results an OGTT should be routinely performed in patients with known or suspected coronary artery disease undergoing coronary angiography for diagnosis of diabetes, as HbA1c measurements alone appear to miss a substantial proportion of patients. These findings are of high clinical relevance with regard to optimal coronary revascularization procedure chosen in catheterization laboratories, preferably drug-eluting stents in cases of diabetes mellitus or newly detected diabetes mellitus and preferably coronary bypass surgery in diabetics with multi-vessel disease and high SYNTAX scores.

Atrial fibrillation and diabetes mellitus. Correlation, co-existence, and coagulation therapy.

Epidemiological studies have reported on the association between diabetes mellitus (DM) and subsequent risk of atrial fibrillation (AF) with inconsistent results. Individuals with DM present with an increased risk (approximate 40%) of subsequent AF compared with unaffected individuals, but the mechanisms underlying the relationship between DM and AF remains speculative. Both entities share common risk factors and, thus, seem to be closely associated with each other. Obviously, the quality of glycemic control is directly related with the risk for AF; the risk is higher with longer duration of treated diabetes and poorer glycemic control. Future research should identify approaches to reduce the risk of AF in people with diabetes by means of consequent screening and anti-coagulation therapy.

[Diabetes mellitus and periodontitis. Bidirectional relationship and clinical implications. A consensus document]. / Diabetes mellitus und Parodontitis. Wechselbeziehung und klinische Implikationen. Ein Konsensuspapier.

Diabetes and periodontitis are chronic diseases with an increasing prevalence in the German population. There is a bi-directional relationship between both diseases. Diabetes promotes the occurrence, the progression and the severity of periodontitis. Periodontitis complicates the glycemic control of diabetes, increases the risk of diabetes-associated complications and possibly even of its onset. In view of the existing evidence, that is still not sufficiently communicated within the medical community, an expert panel consisting of four diabetologists and four periodontists has addressed the following questions: What is the effect of diabetes mellitus on periodontitis and on periodontal therapy? What is the effect of periodontitis on diabetes mellitus? What are the practical consequences, that result for interdisciplinary treatment strategies? The treatment of periodontal infections should become an integral part of the management of diabetes, whereas glycemic control is a prerequisite for successful periodontal therapy.

[Challenge in diabetes therapy: effects of glitazones beyond blood glucose control]. / Herausforderung Diabetestherapie: Effekte der Glitazone jenseits der Blutzuckerkontrolle.

Not just since the results of ACCORD, ADVANCE and VADT were published, it is clear that lowering blood glucose alone does not reduce the cardiovascular risk of patients with type 2 diabetes. In fact, many studies also indicate that some treatment strategies may even have adverse effects. To treat type 2 diabetes appropriately, the co-morbidities such as diabetic dyslipidaemia, hypertension or nephropathy must also be taken into account. Thiazolidinediones reduce insulin resistance thus allowing to direct the treatment of type 2 diabetes towards its pathophysiologic origin. Due to their mechanism of action, thiazolidinediones not only lower blood glucose but have also beneficial effects on inflammatory and atherogenic parameters, blood pressure and microalbuminuria. Furthermore pioglitazone improves dyslipidaemia and reduces mortality, myocardial infarction and stroke in high risk patients. Effects of rosiglitazone on the cardiovascular risk are yet unclear. Numerous studies document the efficacy and safety of thiazolidinediones and provide a basis for an evidence-based therapeutic approach beyond blood glucose control.

Myocardial sympathetic innervation in diabetic patients with symptomatic coronary artery disease.

AIM: In non-diabetic patients, sympathetic innervation can be preserved even if there is major impairment of myocardial blood supply. Matters may be more complex in diabetic patients because denervation can be caused by cardiac autonomic neuropathy (CAN) or by ischemic injury. Our aim was to determine whether restrictions in myocardial blood supply have a pronounced influence on sympathetic innervation in diabetics and if this effect can be differentiated from CAN. PATIENTS, METHODS: We analyzed 20 diabetics with advanced coronary artery disease (CAD) and without known CAN. We determined quantitative myocardial blood flow using (13)N-ammonia-PET, myocardial viability with (18)F-FDG, and cardiac innervation with (11)C-HED. We investigated the relationship between regional HED retention, blood flow, and coronary flow reserve (CFR). Attenuated heart rate response to adenosine was taken as indicator for CAN (HR ratio). RESULTS: There was minor correlation of segmental stress flow and HED retention (r(2)=0.063, p<0.0001). Correlation improved when stress flow as well as HED retention were normalized to the individual maximum (r(2)=0.162, p<0.0001). In nine patients, a HR ratio <1.2 implicated subclinical CAN. Duration of diabetic disease or glycaemic control (HbA1c) did not correlate with mean HED retention in the viable segments, but with its variation coefficient. CONCLUSIONS: As in non-diabetic patients, a slight correlation exists between CFR and sympathetic innervation. The sensitivity of sympathetic nerves to reductions in CFR does not seem to be increased as compared to the results reported for non-diabetics. Besides impaired blood supply, long duration of diabetic disease and bad glycaemic control also seem to impair sympathetic innervation provoking higher heterogeneity.

[Diabetics in secondary prevention]. / Diabetiker in der Sekundärprävention.

It is well known that diabetics live with a significantly higher incidence of a cardiac insufficiency and that acute ischemia is the main cause of death in this group (75%). The risk of suffering a myocardial infarction after ischemic incidences is significantly higher for diabetics than for patients with normal carbohydrate metabolism. Diabetes mellitus is not only responsible for acute incidences, but also for a higher incidence of chronic coronary diseases. Furthermore a disturbed tolerance glucose value was detected in studies for two-thirds of the patients which could even be proven after complete rehabilitation. It has also been shown that the severity of hyperglycemia is in a close inverse relationship to the volume of the brain tissue which can be saved. For this reason hyperglycemia is possibly a therapeutic aim in case of acute ischemic incidences. Therefore the adjustment of blood sugar should be the primary aim to reduce risk in any cases of vascular incidences.

[Cardiovascular protection in diabetic patients with heart disease in the doctor's office]. / Der herzkranke Diabetiker: Kardiovaskuläres Risiko aufdecken und behandeln.

The long-term care of diabetic patients with heart disease poses a particular challenge. Various combinations of risk factors, progression of the coronary heart disease, and complications with further organic damage by the underlying diabetes, frequently necessitate a differentiated diagnostic work-up and management. This can be implemented only by close cooperation between the various specialities. Structured processes may be useful provided they are correctly applied and implemented. Guideline-based treatment of detected cardiovascular risk factors can improve quality of life, reduce morbidity and cardiovascular mortality and thus save costs over the long term.

[Glucose metabolism]. / Glukosestoffwechsel.

The markedly increased peri-interventional risk (PCI and CABG) in patients with type-2 diabetes mellitus may be reduced by adjusting blood glucose values to a near-normal level. This adjustment should be realized acutely by glucose-insulin-potassium infusions. In long-term therapy, the target value should be achieved independent of the pharmacological principle of blood glucose reduction. Among the available oral antidiabetic agents, metformin, acarbose and glitazones seem to be cardioprotective via pleotropic effects. Given an optimal stent implantation and administration of GP IIb/IIIa inhibitors during coronary interventions, results are similar to those of non-diabetics.

[Diabetic patients after myocardial infarction]. / Diabetiker als Herzinfarktpatienten.

Diabetes mellitus is not just another risk factor for cardiovascular events; it per se defines maximal risk for target organ damage including the cardiovascular system. Diabetes is one of the main drivers in the race towards a higher incidence in cardiovascular disease worldwide. In addition, it is also one of the often unrecognized predecessors of myocardial infarction and sudden cardiac death. About three quarters of patients post-MI show impaired glucose tolerance or full blown diabetes. The MONICA/KORA data have shown that the higher risk for mortality and morbidity in diabetics is maintained past the first event. However, the STENO-2 trial has shown that consequently managing diabetes and concomitant cardiovascular risk factors can significantly reduce the risk for cardiovascular events in this high-risk group.

[Aim, design and methods of the "Hypertension and diabetes screening and awareness" -- (HYDRA) study]. / Ziel, Design und Methodik der "Hypertension and Diabetes Risk Screening and Awareness"-(HYDRA)-Studie.

Aim of the study is a comprehensive clinical-epidemiological description of the prevalence of arterial hypertension and diabetes among primary care patients along with an assessment of doctor's recognition rates and prescription behaviour. The paper describes methods and design of the study and provides background information on the sampling process, instruments used as well as characteristics of doctors and patients. The study is based on a nationally representative sample of 1,912 primary care doctors and 45,000 patients that attended the doctors' office on the target days. The patients were also characterized by laboratory tests. The first stage of study consisted of a comprehensive description of the doctors' characteristics in terms of psychosocial, qualification- and provider aspects as well as attitudes towards hypertension and diabetes and their management. In the second stage all patients completed a questionnaire to describe their health behaviour and attitudes as well as the treatment history and therapy. In the third stage all patients were characterized by their doctors in terms of their diagnostic status and their past and current interventions.

[Management of diabetes and hypertension: how do primary care physicians judge their performance?]. / Wie beurteilen Arzte ihre Versorgungspraxis bei Diabetes mellitus und arterieller Hypertonie? Die "Hypertension and Diabetes Risk Screening and Awareness-(HYDRA)"-Vorstudie.

With regard to the management of hypertension and diabetes, HYDRA reveals that doctors report multiple problems in their everyday practice. Being confronted with an average of 73 patients a day, with almost every second having either diabetes or hypertension, frequently associated with multiple comorbid conditions, the core obstacle is the time factor. Doctors do not have sufficient time to perform diagnostic tests and especially no time for non-drug interventions of any type. Further available treatment guidelines are only used in 1 out of 2 doctors. Further they seem not to affect doctors performance significantly.