Multiple risk factor intervention reduces carotid atherosclerosis in patients with type 2 diabetes.

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.

[Blood glucose self monitoring]. / Blutzuckerselbstkontrolle Update 2023.

Self monitoring of blood glucose contributes to the integrated management of diabetes mellitus. It, thus, should be available for all patients with diabetes mellitus. Self monitoring of blood glucose improves patients safety, quality of life and glucose control. The current article represents the recommendations of the Austrian Diabetes Association for the use of blood glucose self monitoring according to current scientific evidence.

[Inhibition of platelet aggregation (Update 2023)]. / Thrombozytenaggregationshemmer (Update 2023).

Acute thrombotic complications as a key feature of accelerated atherothrombotic disease typically precipitate cardiovascular events and therefore strongly contribute to cardiovascular morbidity and mortality in patients with diabetes. Inhibition of platelet aggregation can reduce the risk for acute atherothrombosis. The present article represents the recommendations of the Austrian Diabetes Association for the use of antiplatelet drugs in patients with diabetes according to current scientific evidence.

[Obesity and type 2 diabetes (Update 2023)]. / Adipositas und Typ-2-Diabetes (Update 2023).

The body mass index (BMI) is a very crude measure of body fatness in individuals. Even normal weight persons can have too much body fat in cases of a lack of muscle mass (sarcopenia), which is why additional measurements of waist circumference and body fatness, e.g. bioimpedance analysis (BIA), are recommended. Lifestyle management including nutrition modification and increase in physical activity are important measures for the prevention and treatment of diabetes. Regarding the treatment of type 2 diabetes, body weight is increasingly used as a secondary target parameter. The choice of anti-diabetic treatment and additional concomitant therapies is increasingly influenced by body weight. The importance of modern GLP­1 agonists and dual GLP­1 GIP agonists increases since these drugs target obesity and type 2 diabetes. Bariatric surgery is at present indicated with a BMI > 35 kg/m2 with concomitant risk factors, such as diabetes and can lead at least to partial diabetes remission but has to be incorporated into an appropriate lifelong care concept.

[Lipids-Diagnosis and therapy in diabetes mellitus (Update 2023)]. / Lipide: Diagnostik und Therapie bei Diabetes mellitus (Update 2023).

Hyper- and dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy to lower LDL cholesterol has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence.

[Diabetes mellitus, coronary artery disease and heart disease (Update 2023)]. / Diabetes mellitus, koronare Herzkrankheit und Herzinsuffizienz (Update 2023).

Diabetes mellitus, cardiovascular disease and heart failure are interacting dynamically. Patients being diagnosed with cardiovascular disease should be screened for diabetes mellitus. Enhanced cardiovascular risk stratification based on biomarkers, symptoms and classical risk factors should be performed in patients with preexisting diabetes mellitus. In patients with previously diagnosed arterosclerotic cardiovascular disease an agent proven to reduce major adverse cardiovascular events or cardiovascular mortality is recommended.

[Diagnosis and insulin therapy of type 1 diabetes mellitus (Update 2023)]. / Diagnostik und Therapie des Typ 1 Diabetes mellitus (Update 2023).

This guideline summarizes diagnosis of type 1 diabetes, including accompanying autoimmune disorders, insulin therapy regimens and glycemic target values.

[Antihyperglycemic treatment guidelines for diabetes mellitus type 2 (Update 2023)]. / Antihyperglykämische Therapie bei Diabetes mellitus Typ 2 (Update 2023).

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

Chronic TNF-α neutralization does not improve insulin resistance or endothelial function in "healthy" men with metabolic syndrome.

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.

Admission proinsulin is associated with mortality in patients with admission hyperglycemia during acute coronary syndrome: results from a pilot observational study.

BACKGROUND: Acute hyperglycemia (AHG) is associated with mortality in patients with acute coronary syndrome (ACS). The extent to which hyperproinsulinemia contributes to worse clinical outcomes for this specific patient population is unknown. METHODS: We included 308 consecutive ACS patients who underwent coronary angioplasty in this pilot observational study. Patients were separated into 3 groups: patients with proven diabetes mellitus (DM group) (n =55), nondiabetic patients with a normal glucose concentration at admission (NAG group) (n =175), and nondiabetic patients with AHG at presentation (AHG group) (n =78). Blood samples for glucose, insulin, and proinsulin measurements were obtained at admission. The primary end point of the study was all-cause mortality, which was assessed at a mean follow-up of 19 months (interquartile range, 12-28 months). RESULTS: Patients in the AHG and DM groups had significantly (P =0.048) higher all-cause mortality compared with the NAG group. A univariate Cox regression analysis revealed that the proinsulin concentration was significantly associated with all-cause mortality for all study participants (hazard ratio, 1.013; 95% CI, 1.002-1.024; P =0.023). AHG patients with increased proinsulin concentrations showed a mortality rate similar to that of DM patients but had a significantly higher mortality rate than patients with AHG and a low proinsulin concentration (χ² =7.57; P =0.006) and patients with NAG (with or without increased proinsulin) [χ² =7.66 (P =0.006) and 13.98 (P < 0.001), respectively]. A multivariate regression analysis revealed that the concentrations of glucose and proinsulin at admission were significant (P =0.002) predictors of all-cause mortality. CONCLUSIONS: An increased proinsulin concentration may be a marker for mortality in ACS patients with hyperglycemia at admission and without known diabetes. Further studies are needed to evaluate the role of metabolic parameters such as proinsulin.

DNA repair gene ERCC2 polymorphisms and risk of squamous cell carcinoma of the head and neck.

INTRODUCTION: Genetic aberrations of DNA repair enzymes are known to be common events and to be associated with different cancer entities. Aim of the following study was to analyze the genetic association of single nucleotide polymorphisms (SNP) of the DNA repair genes with the risk of squamous cell carcinoma of the head and neck (HNSCC). MATERIALS AND METHODS: Genetic variants ERCC2 Lys751Gln (rs13181), ERCC2 Asp312Asn (rs1799793), XRCC1 Arg194Trp (rs1799782); XRCC1 Gln399Arg (rs25487), XRCC1 Arg280His (rs25489) and XRCC3 Thr241Met (rs861539) were analyzed in a primary study group comprising 169 patients with histologically confirmed HNSCC and 463 healthy control subjects. Polymorphisms associated with HNSCC were furthermore analyzed in an independent replication study including 125 HNSCC. RESULTS: Only the ERCC2 751 Gln/Gln genotype was associated with HNSCC in the primary study (p=0.033) and in the replication study (p=0.023), resulting in an overall odds ratio of 0.54 (95% confidence interval 0.35-0.92; p=0.006). CONCLUSION: Carriers of the homozygous ERCC2 751 Gln/Gln genotype may be at lower risk for HNSCC.

Glycaemic control in acute coronary syndromes: prognostic value and therapeutic options.

Type 2 diabetes and acute coronary syndromes (ACS) are widely interconnected. Individuals with type 2 diabetes are more likely than non-diabetic subjects to experience silent or manifest episodes of myocardial ischaemia as the first presentation of coronary artery disease. Insulin resistance, inflammation, microvascular disease, and a tendency to thrombosis are common in these patients. Intensive blood glucose control with intravenous insulin infusion has been demonstrated to significantly reduce morbidity and mortality in critically ill hyperglycaemic patients admitted to an intensive care unit (ICU). Direct glucose toxicity likely plays a crucial role in explaining the clinical benefits of intensive insulin therapy in such critical patients. However, the difficult implementation of nurse-driven protocols for insulin infusion able to lead to rapid and effective blood glucose control without significant episodes of hypoglycaemia has led to poor implementations of insulin infusion protocols in coronary care units, and cardiologists now to consider alternative drugs for this purpose. New intravenous or oral agents include the incretin glucagon-like peptide 1 (GLP1), its analogues, and dipeptidyl peptidase-4 inhibitors, which potentiate the activity of GLP1 and thus enhance glucose-dependent insulin secretion. Improved glycaemic control with protective effects on myocardial and vascular tissues, with lesser side effects and a better therapeutic compliance, may represent an important therapeutic potential for this class of drugs in acutely ill patients in general and patients with ACS in particular. Such drugs should be known by practicing cardiologists for their possible use in ICUs in the years to come.

Post-challenge hyperglycaemia is strongly associated with future macrovascular events and total mortality in angiographied coronary patients.

AIMS: The prevalence of post-challenge hyperglycaemia in coronary patients is high. Until now, it is unclear whether post-challenge hyperglycaemia is associated with an increased risk for future macrovascular events in this clinically important patient population. METHODS AND RESULTS: We enrolled 1040 patients undergoing coronary angiography for the evaluation of suspected or established coronary artery disease. In patients without previously established diabetes mellitus, an oral glucose tolerance test (oGTT) was performed. Prospectively, mortality and macrovascular events were recorded over a mean follow-up period of 3.8 years. From our patients, 394 had normal glucose tolerance (NGT), 280 post-challenge hyperglycaemia (this subgroup includes both impaired glucose tolerance and post-challenge diabetes) and 366 had conventional diabetes. The incidence of macrovascular events was significantly higher in patients with post-challenge hyperglycaemia as well as in patients with conventional diabetes than in subjects with NGT (23.6 and 29.5% vs. 18.5%; P = 0.013 and P < 0.001, respectively). Adjusted hazard ratios were 1.46 (95% CI 1.03-2.07, P = 0.033) for patients with post-challenge hyperglycaemia and 1.73 (1.25-2.37, P = 0.001) for patients with conventional diabetes. CONCLUSION: Post-challenge hyperglycaemia is associated with future macrovascular events in patients undergoing coronary angiography for the evaluation of stable coronary artery disease (CAD). Oral glucose tolerance tests in this high-risk population thus identify patients with a particularly unfavourable prognosis.

The doubled burden of diabetic bone disease: hip fracture and post-hip fracture mortality.

OBJECTIVE: Patients with diabetes have an increased risk of osteoporosis and shorter life expectancy. Hip fracture (HF) is the most serious consequence of osteoporosis and is associated with increased mortality risk. We aimed to assess the association of antidiabetic medications with HF and the post-hip fracture mortality risk among diabetic patients ≥50 years. DESIGN: In this nationwide case-control study 53 992 HF cases and 112 144 age-, sex- and region-matched non-hip fracture controls were analyzed. A cohort of hip-fractured diabetic patients were followed-up for an all-cause mortality. METHODS: We defined three groups of diabetic patients based on a prescription of antidiabetic medications: group 1 treated with insulin monotherapy (G1DM), group 2 (G2DM) treated with blood glucose-lowering drugs (BGLD) only, group 3 on a combined BGLD and insulin therapy (G3DM). We applied logistic regression and Cox regression. RESULTS: We identified 2757 G1DM patients, 15 310 G2DM patients, 3775 G3DM patients and 144 294 patients without any antidiabetic treatment. All three groups of diabetic patients had increased odds of HF compared to controls. G1DM patients aged 50-64 years (aOR: 4.80, 95% CI: 3.22-7.17) and G3DM patients (aOR: 1.39, 95% CI: 1.02-1.88) showed the highest HF odds, whereas G2DM patients had 18% decrease in HF odds than their non-diabetic controls (aOR: 0.82, 95% CI: 0.69-0.99). All diabetic patients had increased post-hip fracture mortality risk compared to non-diabetic controls. The highest mortality hazard was observed in G1DM patients, being greater for women than men (HR: 1.71, 95% CI: 1.55-1.89 and HR: 1.44, 95% CI: 1.27-1.64, respectively). CONCLUSIONS: Antidiabetic medications increase the probability of HF. Diabetic patients, who sustained HF have a higher mortality risk than non-diabetic patients.

Integrin alpha-2 and beta-3 gene polymorphisms and colorectal cancer risk.

BACKGROUND AND AIMS: Integrins such as alpha(2)beta(1), alpha(IIb)beta(3), and alpha(v)beta(3) have been suggested as key players for cancer development and progression. Several polymorphisms affecting these molecules, two in integrin alpha(2) (ITGA2 807C>T and 1648G>A) and one in beta(3) (ITGB3 176T>C), influence their levels, structure, and possibly their function. To analyze the role of ITGA2 and ITGB3 polymorphisms for colorectal cancer risk and clinical presentation, we performed a case-control study. MATERIALS AND METHODS: Four hundred thirty-three colorectal cancer patients and 433 healthy sex- and age-matched control subjects were investigated. ITGA2 and ITGB3 polymorphisms were determined by 5'-nuclease assays. RESULTS/FINDINGS: The ITGA2 807C>T polymorphism was associated with reduced colorectal cancer risk. In a codominant model, the odds ratio for each additional 807-T allele for colorectal cancer was 0.77 (95% confidence interval 0.64-0.94; p = 0.011). The ITGA2 1648G> and the ITGB3 176T>C polymorphism were not associated with colorectal cancer. None of the three polymorphisms investigated was associated with tumor size, histological grade, presence of primary lymph node metastases, tumor stage, or age at diagnosis. INTERPRETATION/CONCLUSION: We conclude that the ITGA2 807C>T polymorphism may be associated with reduced colorectal cancer risk.

[The significance of long acting insulin analogues in the treatment of type 2 diabetes mellitus]. / Stellenwert von Langzeit-Insulin-Analoga in der Therapie des Diabetes mellitus Typ 2.

Between 5 and 10% of the European population suffers from diabetes, and its prevalence is constantly rising, in Austria like in other countries. The main goals in the treatment of diabetes mellitus are the prevention of complications and organ damage, the prevention of severe hypo- and hyperglycaemia and the preservation of quality of life. Many patients with type 2 diabetes become insulin-dependent in the course of their disease. The application of a long acting insulin or insulin analogue is the simplest way of initiating an insulin therapy and is in accordance with current guidelines. Current scientific evidence shows that the use of long acting insulin analogues for type 2 diabetes; which can no longer be sufficiently controlled with oral antidiabetic agents, is simple, safe and efficacious. Thus, this treatment option should be available without any restrictions to physicians and patients in order to facilitate the beginning of an insulin regime. This position paper summarises up the current evidence concerning this subject.

[Blood glucose self monitoring (Update 2019)]. / Blutzuckerselbstkontrolle (Update 2019).

Self monitoring of blood glucose contributes to the integrated management of diabetes mellitus. It, thus, should be available for all patients with diabetes mellitus. Self monitoring of blood glucose improves patients safety, quality of life and glucose control. The current article represents the recommendations of the Austrian Diabetes Association for the use of blood glucose self monitoring according to current scientific evidence.

[Inhibition of platelet aggregation (Update 2019)]. / Thrombozytenaggregationshemmer (Update 2019).

Acute thrombotic complications as a key feature of accelerated atherothrombotic disease typically precipitate cardiovascular events and therefore strongly contribute to cardiovascular morbidity and mortality in diabetic patients. Inhibition of platelet aggregation can reduce the risk for acute atherothrombosis. The present article represents the recommendations of the Austrian Diabetes Association for the use of antiplatelet drugs in diabetic patients according to current scientific evidence.

["Diabesity"-Obesity and type 2 diabetes (Update 2019)]. / "Diabesity" ­ Adipositas und Typ-2-Diabetes (Update 2019).

For several years obesity and type 2 diabetes have been increasingly summarized under the name "diabesity". This is due to the fact that in most cases obesity precedes diabetes and is the most important risk factor for the worldwide increase of type 2 diabetes. The body mass index (BMI) is a very crude measure of body fatness in individuals. Even normal weight persons can have too much body fat in cases of a lack of muscle mass (sarcopenia), which is why additional measurements of waist circumference and body fatness, e. g. bioimpedance analysis (BIA), are recommended. Lifestyle management including nutrition modification and increase in physical activity are important measures for the prevention and treatment of diabetes. Regarding the treatment of type 2 diabetes, body weight is increasingly used as a secondary target parameter. The choice of anti-diabetic treatment and also concomitant treatment is increasingly influenced by body weight. The significance of anti-obesity medications in the treatment of type 2 diabetes will have to be clarified by future studies with body weight as the primary endpoint. Bariatric surgery is at present indicated with a BMI >35 kg/m2 with concomitant risk factors, such as diabetes and can lead at least to partial diabetes remission but has to be incorporated into an appropriate lifelong care concept.

[Diagnosis and insulin therapy of type 1 diabetes mellitus (Update 2019)]. / Diagnostik und Therapie des Typ 1 Diabetes mellitus (Update 2019).

This guideline summarizes diagnosis of type 1 diabetes, including accompanying autoimmune disorders, insulin therapy regimens and glycemic target values.