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ZusammenfassungDie Hyperglykämie ist wesentlich an der Entstehung der Spätkomplikationen bei an Diabetes mellitus Typ 2 erkrankten Patienten/Patientinnen beteiligt. Während Lebensstilmaßnahmen die Eckpfeiler jeder Diabetestherapie bleiben, benötigen im Verlauf die meisten Patienten/Patientinnen mit Typ 2 Diabetes eine medikamentöse Therapie. Bei der Definition individueller Behandlungsziele stellen die Therapiesicherheit, die Effektivität sowie substanzspezifische, kardiovaskuläre Effekte der Therapie die wichtigsten Faktoren dar. In dieser Leitlinie haben wir die rezenten evidenzbasierten Daten für die klinische Praxis zusammengestellt.

ZusammenfassungHypertonie ist eine sehr häufige Komorbidität bei Patient:innen mit Diabetes mellitus, die – wenn unzureichend behandelt – signifikant zur erhöhten Mortalität und zum Auftreten von mikrovaskulären und makrovaskulären Komplikationen beiträgt. Eine Individualisierung der Blutdruckzielwerte in Abhängigkeit vom Patient:innenalter und vom Vorliegen bestimmter vaskulärer Komplikationen wird heute weltweit diskutiert. Blutdruckzielwerte um 130/80 mm Hg waren in den Studien mit der geringsten Ereignisrate an Komplikationen assoziiert, wobei die Blutdruckzielwerte je nach Alter und Komorbiditäten individualisiert werden sollten; am wichtigsten ist für die meisten Patient:innen, dass ein Blutdruck

Purpose Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease. Materials and Methods We included 68 non-diabetic patients who underwent bariatric surgery. Serum DPP4 activity was measured using a fluorogenic substrate before and after surgery. Results Results: After a median follow-up period of 12 (IQR 11-17) months, median serum DPP4 activity decreased from 230 (IQR: 194-273) to 193 (164-252) pmol/min (p=0.012). The decrease in DPP4 activity was significantly correlated with decreases in BMI, improved cholesterol levels, reduced hepatic injury markers as well as improved post-prandial insulin sensitivity. After multivariable adjustment, ΔDPP4 activity remained significantly associated with Δcholesterol (beta=0.341, p=0.025), ΔLDL cholesterol (beta=0.350, p=0.019), Δgamma-glutamyltransferase (beta=0.323, p=0.040) and ΔMatsuda index (beta=-0.386, p=0.045). Conclusion We demonstrated that weight loss induced by bariatric surgery results in decreased circulating DPP4 activity beyond the initial phase of weight loss. The associations between decreased DPP4 activity and improved cholesterol levels as well as hepatic injury markers point towards pleiotropic effects of DPP4 beyond glucose metabolism which warrant further investigation.

Patients with Covid-19 place new challenges on the management of type 2 diabetes, including the questions of whether glucose-lowering therapy should be adjusted during infection and how to manage a return to normal care after resolution of Covid-19 symptoms. Due to the sudden onset of the pandemic, physicians have by necessity made such important clinical decisions in the absence of robust evidence or consistent guidelines. The risk to patients is compounded by the prevalence of cardiovascular disease in this population, which alongside diabetes is a major risk factor for severe disease and mortality in Covid-19. We convened as experts from the Central and Eastern European region to consider what advice we can provide in the setting of type 2 diabetes and Covid-19, considering the evidence before, during and after infection. We review recommendations that have been published to date, and consider the best available—but currently limited—evidence from large observational studies and the DARE-19 randomized control trial. Notably, we find a lack of guidance on restarting patients on optimal antidiabetic therapy after recovering from Covid-19, and suggest that this may provide an opportunity to optimize treatment and counter clinical inertia that predates the pandemic. Furthermore, we emphasize that optimization applies not only to glycaemic control, but other factors such as cardiorenal protection. While we look forward to the emergence of new evidence that we hope will address these gaps, in the interim we provide a perspective, based on our collective clinical experience, on how best to manage glucose-lowering therapy as patients with Covid-19 recover from their disease and return to normal care.

Recent epidemiological investigations have shown that approximately 2-3% of all Austrians suffer from diabetes with renal involvement, i. e. 250,000 people in Austria are affected. The risk of occurrence and progression of this disease can be ameliorated by life style interventions as well as optimization of blood pressure, blood glucose levels and special drug classes. The present article represents the joint recommendations of the Austrian Diabetes Association and the Austrian Society for Nephrology for the diagnostics and treatment strategies of diabetic kidney disease.

Hypertonie ist eine sehr haufige Komorbiditat bei Patienten mit Diabetes mellitus, die – wenn unzureichend behandelt – signifikant zur erhohten Mortalitat und zum Auftreten von mikrovaskularen und makrovaskularen Komplikationen beitragt. Eine Individualisierung der Blutdruckzielwerte in Abhangigkeit vom Patientenalter und vom Vorliegen bestimmter vaskularer Komplikationen wird heute weltweit diskutiert. Blutdruckzielwerte um 130/80 mm Hg waren in den Studien mit der geringsten Ereignisrate an Komplikationen assoziiert. ACE-Hemmer und Angiotensin-Rezeptorblocker sollen in der Hypertonie-Therapie bei Patienten mit Diabetes mellitus bevorzugt werden. Calciumantagonisten und Diuretika sind in der Second-Line-Therapie oft notwendig. Nach Erreichung der Zielwerte muss die antihypertensive Therapie fortgefuhrt werden, wobei regelmasige Blutdruckmessungen durch die Patienten fur die Optimierung der Blutdruckeinstellung sehr hilfreich sind. Neuere Antidiabetika wie SGLT2-Inhibitoren oder GLP1-Rezeptoragonisten haben tragen ebenfalls zur Blutdrucksenkung bei.

The disclosure of proven cardiorenal benefits with certain antidiabetic agents was supposed to herald a new era in the management of type 2 diabetes (T2D), especially for the many patients with T2D who are at high risk for cardiovascular and renal events. However, as the evidence in favour of various sodium–glucose transporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) accumulates, prescriptions of these agents continue to stagnate, even among eligible, at-risk patients. By contrast, dipeptidyl peptidase-4 inhibitors (DPP-4i) DPP-4i remain more widely used than SGLT2i and GLP-1 RA in these patients, despite a similar cost to SGLT2i and a large body of evidence showing no clear benefit on cardiorenal outcomes. We are a group of diabetologists united by a shared concern that clinical inertia is preventing these patients from receiving life-saving treatments, as well as placing them at greater risk of hospitalisation for heart failure and progression of renal disease. We propose a manifesto for change, in order to increase uptake of SGLT2i and GLP-1 RA in appropriate patients as a matter of urgency, especially those who could be readily switched from an agent without proven cardiorenal benefit. Central to our manifesto is a shift from linear treatment algorithms based on HbA1c target setting to parallel, independent considerations of atherosclerotic cardiovascular disease, heart failure and renal risks, in accordance with newly updated guidelines. Finally, we call upon all colleagues to play their part in implementing our manifesto at a local level, ensuring that patients do not pay a heavy price for continued clinical inertia in T2D.

Hyperglycemia significantly contributes to micro- and macrovascular 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 in regard of optimal therapeutic efficacy and high therapeutic safety is of great importance. In this guideline we present the best and most current evidence-based clinical practice data for healthcare professionals.

Blood pressure lowering is one of the most important interventions for reducing the vascular complications and mortality in patients with diabetes mellitus. Recent studies indicate that the optimal blood pressure level might be in the range between 130-140 mmHg systolic and 80‒90 mmHg diastolic. Lower blood pressure levels (e.g. 120/80 mmHg) can further reduce the risk for stroke and diabetic nephropathy, but are associated with increased cardiovascular mortality. In particular, very low blood pressure levels (

Aims These recommendations aim to improve care for patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk in Central and Eastern Europe. Cardiovascular disease (CVD) and/or chronic kidney disease (CKD) are major interdependent comorbidities in patients with T2D, accounting for 50% of mortality. Following recent CV outcomes trial (CVOT) results, including those from EMPA-REG OUTCOME®, LEADER®, SUSTAIN™-6 and, most recently, the CANVAS study, it is essential to develop regional expert consensus recommendations to aid physicians in interpreting these newest data to clinical practice. Methods The Central and Eastern European Diabetes Expert Group (CEEDEG) followed a Delphi method to develop treatment algorithms to aid physicians in the clinical management of patients with T2D at high CV risk. Results In light of the latest CVOT results, and in particular the EMPA-REG OUTCOME® and LEADER® trials, the diagnosis, assessment, treatment choice and monitoring of patients with T2D and established CVD and/or CKD have been considered together with existing guidelines and presented in two reference algorithms. In addition, adherence, special prescribing considerations and a proposed multidisciplinary management approach have been discussed and are presented with the proposed algorithms. Conclusions The latest available high-level evidence on glucose-lowering drugs has enabled CEEDEG to develop practical consensus recommendations for patients with established CVD and/or CKD. These recommendations represent an update to international and country-level guidelines used for these patients, with the aim of providing a resource not only to endocrinologists, but to cardiologists, nephrologists and primary care physicians in the region. Electronic supplementary material The online version of this article (doi:10.1186/s12933-017-0622-7) contains supplementary material, which is available to authorized users.

In a new study published in The Lancet Diabetes & Endocrinology, metformin use is associated with significantly increased all-cause mortality in patients with type 2 diabetes mellitus and stage 5 chronic kidney disease (CKD). The findings support current recommendations that metformin should not be used in patients with stage 5 CKD.

Die Blutdrucksenkung ist einer der wichtigsten Masnahmen um die vaskularen Komplikationen und die Mortalitat bei Patienten mit Diabetes mellitus zu senken. Rezente Studien zeigen, dass die optimalen Blutdruckzielwerte zwischen 130–135 mmHg systolisch und 80 mmHg diastolisch liegen durften. Niedrigere Blutdruckzielwerte (z. B. 120/80 mmHg) konnen zwar das Risiko fur Schlaganfall und diabetische Nephroopathie weiter senken, sind aber mit einer erhohten Kardiovaskularen Mortalitat assoziiert. Sehr niedrige Blutdruckwerte (< 120 mmHg) sollten insbesondere bei Patienten mit koronarer Herzerkrankung oder mit peripherer arterieller Verschlusskrankheit unbedingt vermieden werden. Der Grosteil der Patienten mit Diabetes und Hypertonie benotigt eine antihypertensive Kombinationstherapie, wobei ACE-Inhibitoren oder Angiotensin-II Receptor Blocker in der first-line Therapie eingesetzt werden sollen.

Diabetische Nephropathie ist die fuhrende Ursache der Nierenersatztherapie und die haufigste Nierenkrankheit geworden. Die Entwicklung und das Fortschreiten kann durch optimierte Therapie beeinflusst werden. Im vorliegenden Artikel werden die gemeinsamen Empfehlungen der Osterreichischen Diabetesgesellschaft und der Osterreichischen Gesellschaft fur Nephrologie dargestellt.

Die Hyperglykamie ist wesentlich an der Entstehung mikro- als auch makrovaskularer Spatkomplikationen bei an Diabetes mellitus Typ 2 erkrankten Patienten beteiligt. Wahrend Lebensstilmasnahmen die Eckpfeiler jeder Diabetestherapie bleiben, benotigen im Verlauf die meisten PatientInnen mit Typ 2 Diabetes eine medikamentose Therapie. Bei der Definition individueller Behandlungsziele stellen die Therapiesicherheit bzw. die Effektivitat der Therapie die wichtigsten Faktoren dar. In dieser Leitlinie haben wir die rezenten evidenzbasierten Daten fur die klinische Praxis zusammengestellt.

The increased cardiovascular (CV) disease risk in patients with morbid obesity (MO) cannot be fully explained by traditional CV risk factors. Activation of the receptor of Advanced Glycation Endproducts (RAGE) leads to inflammation via the NF κβ (nuclear factor κβ) pathway. The soluble form of RAGE (sRAGE), which is present in plasma, can bind to ligands of RAGE and avoids interaction of RAGE with proinflammatory ligands. We investigated sRAGE levels in patients with MO and compared them with healthy lean controls (CO), before and after bariatric surgery.We conducted a cross-sectional study and a 24-month longitudinal study.We included 85 patients (mean age: 41 ± 12 years; mean body mass index (BMI): 45.4 ± 7.9 kg m(-2)) with MO in comparison with 40 CO (mean age: 42 ± 13 years; mean BMI: 26.0 ± 5.5 kg m(-2)). All patients were investigated before and 2 years after bariatric surgery. Apart from weight and CV risk markers (blood pressure, lipids), a glucose tolerance test (75 g), renal and inflammation parameters were assessed. sRAGE levels were assessed by a commercial ELISA. To investigate the associations of the observed reductions of values, delta (Δ) of parameters were calculated.Patients with MO had significant lower sRAGE levels than CO: 1010 ± 514 vs 1501 ± 674 pg ml(-1); P0.001. In the longitudinal study, sRAGE levels increased significantly after bariatric surgery from 1010 ± 514 to 1261 ± 710 pg ml(-1); P=0.008. In the correlation analysis, ΔsRAGE levels were associated with Δ1-h and Δ2-h postprandial glucose, Δfasting insulin, Δ2-h postprandial insulin, ΔHOMA (homeostatic model assessment)-insulin resistance (ΔHOMA-IR), Δγ-glutamyl transferase and Δtriglycerides. In a multivariate model, Δ1-h and Δ2-h postprandial glucose, Δ2-h postprandial insulin and ΔHOMA-IR predicted ΔsRAGE.Patients with MO have significantly lower sRAGE levels compared with non-obese CO, but sRAGE levels increase significantly after weight loss induced by bariatric surgery. As high sRAGE levels inhibit the activation of inflammatory pathways, our results might help understand the beneficial effects of bariatric surgery regarding CV morbidity and mortality.

Diabetes Care Austria war eine Osterreichweite Erhebung der Typ 2 Diabetestherapie bei niedergelassenen AllgemeinmedizinerInnen. Ende 2009 wurden 5.385 niedergelassene AllgemeinmedizinerInnen kontaktiert, von denen 101 an der Datenerhebung teilnahmen. Eine Querschnittstichprobe aus allen 9 osterreichischen Bundeslandern mit 1.513 Typ 2 DiabetikerInnen wurde untersucht. Neben demographischen Daten, Diabetestherapie und Qualitat der Stoffwechselkontrolle wurden mikro- und makrovaskulare Komplikationen in Abhangigkeit von der in 6 Klassen kategorisierten Diabetesdauer untersucht. Insgesamt wurden 1.513 Typ 2 Diabetiker mit einem mittleren Alter von 65,4 ± 10,7 Jahren und einer Diabetesdauer von 8,7 ± 7,3 Jahren erfasst. Metformin wurde in allen Kategorien der Diabetesdauer bei uber 50 % der PatientInnen angewendet. Die Verwendung von Sulfonylharnstoffen nahm von 25 % bei einer Diabetesdauer von weniger als 3 Jahren auf uber 40 % bei einer Diabetesdauer von mehr als 15 Jahren signifikant (p < 0,001) zu. Die Verschreibung von Glitazonen nahm signifikant (p = 0,02) mit der Diabetesdauer zu. DPP-4 Inhibitoren wurden bei uber 5 % der Patienten (mit einem Haufigkeitsmaximum von 13 % bei einer Diabetesdauer von 4–9 Jahren, p < 0,001) eingesetzt Der mittlere HbA1c-Wert lag in allen Gruppen unter 7,5 % und war mit 7,0 ± 1,2 % in der Gruppe mit der kurzesten Diabetesdauer signifikant (p < 0,01) niedriger als in allen anderen Gruppen. Diabetes Care Austria ermoglicht reprasentative Daten bezuglich der Diabetestherapie fur bei niedergelassenen AllgemeinmedizinerInnen behandelte Typ 2 DiabetikerInnen. Ein mittlerer HbA1c-Wert von 7,2 % belegt die erfolgreiche Diabetestherapie. Eine Insulintherapie wird relativ spat aber suffizient initiiert, wie vergleichbare HbA1c-Werte bei Patienten mit einer Diabetesdauer von 4 bis uber 15 Jahren zeigen.

At the time of diagnosis of type 2 diabetes (T2D), patients already have varying degrees of beta-cell dysfunction and insulin resistance and the defects continue to deteriorate despite treatment. We examined insulin secretion impairment and insulin resistance in overweight patients with T2D who had metformin failure, with elevated HbA1c at maximal metformin dose. Patients (N = 1,039) were examined at entry to the European Exenatide (EUREXA) clinical trial of add-on exenatide versus sulphonylurea. Mean (±SD) age was 57 ± 10 years, and BMI was 32.4 ± 4.1 kg/m(2). All patients underwent an oral glucose tolerance test; HOMA-IR, HOMA-B, ∆I(30)/∆G(30), disposition index and pro-insulin/insulin ratio were evaluated in relation to stratified HbA1c levels (≤7.3, >7.3-8.2, >8.2%) and duration of diabetes (

Es besteht kein Zweifel, dass die metabolische Chirurgie eine sehr effektive therapeutische Option bei morbid adiposen Patienten mit Typ-2-Diabetes und einem „Body Mass Index“ (BMI) >45 kg/m2 darstellt, insbesondere dann, wenn die Diabetesdauer kurz ist und die Hyperinsulinamie und die Insulinresistenz sehr ausgepragt sind. Bei Patienten mit einem niedrigeren BMI-Ausgangswert sind die Ergebnisse weitaus weniger beeindruckend, wobei dies darauf zuruckzufuhren sein konnte, dass bei diesen Patienten der Insulinmangel schon ausgepragter ist und die hochgradige Insulinresistenz weniger dominierend. Ob die akute „Heilung“ tatsachlich langfristig fortbesteht und tatsachlich zu einer verminderten kardiovaskularen Morbiditat und Mortalitat fuhrt und auch die Krebsmortalitat bei Patienten mit Typ-2-Diabetes langfristig reduzieren kann, ist Gegenstand laufender Studien. Gegenwartig sind noch viele Fragen offen: Welche Patienten profitieren besonders von der metabolischen Chirurgie? Sind eine langere Diabetesdauer und eine weniger ausgepragte Adipositas limitierende Faktoren fur eine erfolgreiche Ruckbildung des Typ-2-Diabetes? Eine vor Kurzem von der Havard-Universitat initiierte kontrollierte Studie (http://clinicaltrials.gov/ct2/show/NCT01073020?term=joslin&rank=8) soll klaren, ob die gegenwartig durchgefuhrten bariatrischen Operationsverfahren multidisziplinaren Programmen mit dem Ziel der Lebensstilanderung und Gewichtsreduktion bei Patienten mit Typ-2-Diabetes und weniger ausgepragter Adipositas (Klasse 1 und 2) tatsachlich uberlegen sind.

Patients suffering from morbid obesity (MO) have an increased cardiovascular morbidity and mortality. This increased cardiovascular burden is believed to be caused by a sub-inflammatory state through an increased secretion of monocyte chemoattractant protein-1 (MCP-1) by the adipose tissue, resulting in insulin resistance (IR) and type 2 diabetes mellitus (T2DM). YKL-40, which is elevated in inflammatory processes in T2DM and IR and in ruptured plaques, might as well be involved in the increased cardiovascular burden of MO patients. The present study aims to study the level of YKL-40 in MO patients before and after weight loss as well as to investigate the relationship between YKL-40, IR, MCP-1, and obesity.We investigated YKL-40 levels in serum samples of both 17 morbidly obese patients before and after bariatric surgery and 17 healthy controls. YKL-40 levels were determined in serum samples by enzyme-linked immunosorbent assay.After a mean follow-up of 17.4 months and a mean weight loss of 40 kg through bariatric surgery, YKL-40 levels declined by 30.5% (p = 0.027). Multiple linear regression analysis revealed that only preoperative MCP-1 values remained independently and significantly (p = 0.001) associated with preoperative YKL-40 levels. Moreover, delta (change) homeostasis model assessment of insulin resistance (HOMA-IR) values remained independently and significantly (p = 0.002) associated with delta YKL-40 levels.We show for the first time that elevated levels of YKL-40 in MO patients decreased after massive weight loss via bariatric surgery. YKL-40 was correlated with HOMA-IR and fasting insulin levels, indicating a role in developing processes of IR and T2DM. The tight association of MCP-1 (plaque development) and YKL-40 (plaque rupture) points to a central role of both proteins, contributing to the increased cardiovascular mortality in MO patients.

Ghrelin and obestatin are derived from the same gene but have different effects: Ghrelin stimulates appetite, and previous—albeit inconsistent—data show that obestatin may be involved in satiety. The present study was designed to test the hypothesis that Roux-en-Y gastric bypass (RYGB) surgery and/or the weight loss that reliably results from this procedure would alter levels of ghrelin and obestatin and ghrelin/obestatin ratios in a cohort of morbidly obese women. This is a longitudinal follow-up study in 18 morbidly obese women (mean weight 131.2 kg, mean body mass index [BMI] 47.4). Clinical parameters and fasting serum concentrations of ghrelin, obestatin, triglycerides, low-density lipoprotein cholesterol, glucose, and insulin were measured before and 2 years after RYGB surgery, which was associated with body weight reductions of 41.5 ± 11.6 kg (mean 62.5% excess weight loss). Ghrelin concentrations (−12%, p = 0.022) and ghrelin/obestatin ratios (−14%, p = 0.017) were lower after surgery than before, while obestatin levels did not change. Changes in ghrelin concentrations correlated with changes in insulin levels (r = 0.45, p = 0.011). Most cardiovascular risk factors studied improved postsurgically (p

Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are cosecreted in the same enteroendocrine L-cells of the gut and reported to inhibit food intake additively. However, findings in human studies regarding these peptides are controversial. The aim of this study was to analyze the relationships between fasting PYY, GLP-1, and weight status in morbidly obese patients before and after surgically induced weight loss. Fasting GLP-1, PYY, glucose, and insulin concentrations; blood pressure; and body-mass index (BMI) were determined in 30 morbidly obese adults (mean BMI 45.8, mean age 40 years) before bariatric surgery [Roux-en-Y gastric bypass (RYGB): n = 19; gastric banding (GB): n = 11] and after weight loss (mean 50% excess weight loss) in the course of mean 2 years. GLP-1 concentrations decreased (mean −20 pg/ml; mean −38%; p = 0.001) and PYY concentrations increased (mean +19 pg/ml; mean +19%, p = 0.036) after bariatric surgery. The weight loss and changes of GLP-1 were significantly (p

Background: Morbid obesity is associated with insulin resistance (IR), chronic inflammation and premature atherosclerosis. Since vascular inflammation may contribute to the increased risk of cardiovascular morbidity and mortality of these patients, we studied circulating Interleukin-18 (L-18) and monocyte-chemoattractant-protein-1 (MCP-1) levels in 37 patients with morbid obesity before and after significant weight loss induced by bariatric surgery and their preoperative and postoperative associations with C-reactive protein (CRP) and IR-associated factors. Methods: High sensitivity assays were used to measure concentrations of fasting CRP, IL-18 and MCP-1. Differences between patients before and after bariatric surgery were analyzed by Student's paired t-test. To investigate the associations of the observed reductions of values, delta of parameters were calculated and preoperative, postoperative and delta data were tested by univariate and multivariate linear regression. Results: After a mean follow-up period of 26.5 months and a massive weight loss of 35 kg induced by bariatric surgery, circulating IL-18 levels decreased by 37% (P

Obesity is linked to the insulin resistance syndrome (IRS), type 2 diabetes (T2D) and cardiovascular disease. Markers of chronic subclinical inflammation such as high-sensitive C-reactive protein (hs-CRP) and interleukin 6 (IL-6) are closely related to insulin resistance and obesity. Recent evidence suggests that adiponectin, a protein whose circulating levels are decreased in obesity, has anti-inflammatory properties, and also appears to enhance potently insulin action and therefore appears to function as a signal produced by adipose tissue that influences whole-body glucose metabolism.We investigated the cross-sectional and longitudinal association of adiponectin with CRP and IL-6 in 41 morbidly obese women with different stages of glucose tolerance before and 17 months after significant weight loss induced by gastric surgery. Adiponectin was measured by RIA. CRP and IL-6 were determined by commercially available ELISA systems.Weight loss induced a significant shift from T2D (preoperatively 34% vs postoperatively 2%) to impaired glucose tolerance (IGT) (37% preoperatively vs 30% postoperatively) and normal glucose tolerance (NGT) (29% preoperatively vs 68% postoperatively). Preoperatively adiponectin levels were negatively correlated with CRP (r=-0.59, P0.0006), IL-6 (r=-0.42, P0.02) and leukocytes (r=-0.41, P0.007). After gastroplasty, adiponectin concentrations increased significantly (15.4+/-8.2 vs 19.8+/-6.2 microg/ml, P0.005) associated with changes of weight and body mass index (r=-0.45, P0.007; r=-0.35, P0.04). Furthermore, preoperative CRP was significantly associated with changes in adiponectin even after adjustment for sex, age, preoperative body mass index (BMI) impaired glucose metabolism and changes in BMI and changes in BMI (standardized beta 0.61, P=0.005).Levels of adiponectin, which are associated with markers of chronic subclinical inflammation, could be significantly increased after weight loss in morbidly obese patients. This increase was more pronounced in patients with NGT compared to those with T2D and IGT. Preoperative levels of CRP are predictive for changes of adiponectin after weight loss.

Type 2 diabetes mellitus is a major health problem associated with excess morbidity and mortality. Defects in the action and/or secretion of insulin are the two major abnormalities leading to development of glucose intolerance. Any intervention in the impaired glucose tolerance phase that reduces resistance to insulin or protects the beta-cells, or both, should prevent or delay progression to diabetes. The natural history of type 2 diabetes includes a preceding period of impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) which provides an opportunity for targeted intervention within large communities. As the prevalence of this metabolic disorder is rapidly increasing and current treatment fails to stabilise the disease in most patients, prevention should be considered as a key objective in the near future. Lifestyle intervention studies have consistently shown that quite modest changes can reduce the progression from IGT to diabetes by 50-60%. The Diabetes Prevention Program (DPP) randomised trial has shown that a combined program of weight loss, improvement of diet and increase of physical exercise lowers the risk for development of type 2 diabetes by 58% compared with placebo. It may, however, not be possible to translate these successful findings to larger cohorts or maintain the lifestyle changes longer term. This has lead to consideration of pharmacotherapy. Benefits have been found for metformin, acarbose and troglitazone. Treatment with metformin was less effective than lifestyle modifications, resulting in an average reduction of risk for development of type 2 diabetes by 31% compared with placebo. Similarly, acarbose in the STOP-NIDDM trial reduced the risk of developing type 2 diabetes in patients with IGT by 25%. Remarkably, cardiovascular event rates, in particular myocardial infarction, were significantly reduced when acarbose was used instead of placebo in subjects with glucose intolerance. The ACE inhibitors captopril (CAPPP) or ramipril (HOPE) and the Angiotensin-II receptor antagonist losartan (LIFE) have been shown to reduce the appearance of diabetes by one third when given to patients with hypertension. Since many hypertensive patients are insulin-resistant and have an increased risk in developing type 2 diabetes, the protective effect of these classes of antihypertensive drugs might be explained by their antiinsulin-resistance effects.

The aim of the present study was to investigate the renal effects of long-term treatment with the calcium channel blocker nifedipine in normotensive type 1 diabetic patients with microalbuminuria. In a randomized, double-blind trial, 15 type 1 diabetic patients were treated with either nifedipine (n=8; dosage 30 mg/day) or placebo (n=7) for 12 months. At baseline and after 6 and 12 months of therapy, the albumin excretion rate (UAER, radioimmunoassay), glomerular filtration rate (GFR, chromium 51 ethylenediamine tetra-acetic acid clearance) and renal plasma flow (RPF, iodine 125 hippuran clearance) were determined. Nifedipine treatment caused a significant reduction of UAER after 6 and 12 months (median, Q1/Q3 in mg/24 h): baseline 84 (65/163); 6 months 35 (23/90),P

Background Adrenocortical carcinoma synthesizing solely mineralocorticoids is an unusual disorder which has only been reported in literature in 22 other patients. Methods This case report describes a patient presenting with hypokalaemia, hypertension, metabolic acidosis and a left adrenal tumor. Extensive laboratory testing allowed the diagnosis of pure primary hyperaldosteronism without secretion of other steroids. Results The treatment of choice after establishing the diagnosis biochemically is to remove the tumor surgically. Histologically the lesion within the left adrenal was classified as a benign adrenocortical adenoma. After recurrence of, disease 6 months postoperatively, a widespread retroperitoneal tumor was en bloc resected and malignancy was confirmed by the histological features. When extended total histological examination of the first tumor was performed, capsular invasion was detected in one slice and the diagnosis of adrenocortical cancer was established retrospectively not only on the basis of clinical behavior. Despite precise surgical treatment of the recurrence and chemotherapy, the patient died 14 months after the diagnosis of primary hyperaldosteronism. Conclusions Close biochemical and clinical follow-up examinations are necessary in each patient with hormonlly active tumors. Sometimes only the postoperative course discriminates benign and malignant lesions.

Realizing the importance of carnitine for the lipid and carbohydrate metabolism and the possible role for glucose utilization and myocardial function carnitine concentrations in type I and type II diabetic patients in plasma, erythrocytes and 24 h urine were determined. The plasma levels of carnitine were significantly diminished in type I diabetic patients compared to controls, while carnitine concentrations in erythrocytes and 24 h urine did not differ from controls. Plasma carnitine levels did not change significantly during the diurnial profile. No correlation between HbA1c and carnitine levels was observed in the diabetic patients.

This Practice Point commentary discusses the findings and limitations of a randomized, double-blind study conducted by Parving and colleagues. The study evaluated the renoprotective effects of dual blockade of the renin–angiotensin–aldosterone system by adding aliskiren (an oral, direct renin inhibitor) or placebo to treatment with 100 mg daily losartan in patients who had hypertension and type 2 diabetes with nephropathy. Addition of daily aliskiren for 6 months (150 mg/day for 3 months and 300 mg/day for 3 months) reduced the mean urinary albumin:creatinine ratio by 20% (P

We studied insulin receptor binding and carbohydrate metabolism in 10 patients with severe hyperprolactinaemia and compared the findings with those obtained in 20 healthy control subjects. Insulin binding to monocytes and erythrocytes was significantly decreased in the patients with an excess of prolactin. Scatchard analysis of binding data indicated that a decrease in the number of receptors rather than in receptor affinity seems to be the prevailing cause of lowered binding in hyperprolactinaemic patients. Furthermore, patients with severe hyperprolactinaemia demonstrated significantly elevated blood glucose levels following oral or intravenous glucose load despite having significantly increased insulin levels after glucose administration. The infusion of insulin induced a delayed hypoglycaemic effect and a decreased inhibition of endogenous insulin secretion, as indicated by the suppression of C-peptide in the hyperprolactinaemic patients. The present data indicate that severe hyperprolactinaemia is associated with an insulin-resistant state, which seems to be caused, at least in part, by a down-regulation of insulin receptors.

The interrelationship between Coxsackie B4 (CB4) virus antibodies, islet-cell antibodies and HLA B8 was studied in 67 patients with juvenile-onset diabetes mellitus (JOD). In 41 JOD patients (61%) CB4 antibodies (greater than 1:4) were found. A high prevalence (69%) of significant CB4 antibody titers (greater than 1:64) was observed in patients with age at onset between 11 and 20 years compared with those with age at onset below or over that age-range (27% and 33%, respectively). Islet-cell antibodies (ICA) could be detected only in 11 JOD patients, which is probably due to the relatively long mean duration of disease. However, 8 of them presented with significant CB4 antibody production. Although no correlation between CB4 antibodies and the JOD-associated HLA-antigens (B8, Bw15, Cw3 and B7) could be detected in the entire group of JOD patients, a close association between ICA persistence and HLA B8 was found. Furthermore, in the ICA-positive, moderate or high CB4 antibody titers were prevalent. Thus, the present data point to a possible interrelationship between CB4 virus antibodies, persistent ICA production and HLA B8 in a minor proportion of JOD patients. However, it seems premature to assume direct implication of these factors in the pathogenesis of JOD.

The role of hypertension for the combined occurrence of incipient diabetic nephropathy and diabetic retinopathy (RP) was evaluated in 155 insulin-dependent diabetic patients (74 male/81 female); mean age 32.4±12.2 STD years; mean diabetes duration 12.8±10 STD years). Albumin excretion rate (AER) was measured in 24 hours urine samples by RIA, retinal status was determined by both, fundoscopy and fluorescein angiography. Analysis of the data revealed a statistically significant correlation between the duration of disease and elevated AER (p 15 µg/min). In the group of microalbuminuric patients (>15 µg/min) systolic (p

Depending on their symptomatology 152 cured (i.e., normocalcemic) patients with surgically proven primary hyperparathyroidism (pHPT) showed typical symptoms preoperatively. Besides hypercalcemia and elevated parathyroid hormone levels, 15 patients suffered only from hypertension and/or diffuse osteoporosis and/or complaints caused by the hypercalcemic syndrome (oligosymptomatic patients). Nine patients had no complaints (asymptomatic patients). The long-term clinical course of all patients was analyzed up to 22 years. Although the formation of urinary calculi was stopped in 94% of cases, a deterioration of renal function and hypertension was seen in symptomatic (12.5% and 9.2%, respectively) and oligosymptomatic patients (6.7% and 13.3%, respectively). Renal function and hypertension were unpredictable despite normalization of the hyperactive parathyroid metabolism and were of decisive prognostic significance; 6% died of acute or chronic renal failure, or of the consequences of hypertension. Multiple bone lesions, even large, healed functionally and were of no prognostic significance. In the majority of symptomatic patients gastrointestinal manifestations held postoperatively, but two patients died of acute pancreatitis without gastrointestinal complaints preoperatively. Almost all symptoms of the hypercalcemic syndrome disappeared immediately and permanently in symptomatic and oligosymptomatic patients. No deterioration of renal function and no elevation of blood pressure was observed in cured asymptomatic patients postoperatively. Immediate surgical treatment even in asymptomatic patients may have avoided complications of chronic renal failure or of hypertension. As soon as organic manifestations, even in a mild form, have been established, it seems impossible to predict the course and to prevent an unfavorable clinical outcome.

Hyperlipidamien sind ein haufiger Befund bei Diabetes mellitus. Da neben der Leber auch die Dunndarmmukosa endogene Lipoproteine synthetisiert, war es von Interesse, bei 11 Erwachsenen mit juvenilem Diabetes und bei 7 Patienten mit Altersdiabetes den Lipidgehalt der Dunndarmmukosa zu bestimmen. Als Kontrolle dienten 11 nicht diabetische Patienten. Nach einer Nuchternperiode von 12–14 h erfolgte zunachst eine Blutabnahme zur Bestimmung von Nuchternblutzucker, Serumlipiden und glykosyliertem Hamoglobin AI, daraufhin wurden mittels einer hydraulischen Biopsiesonde oder endoskopisch mehrere Dunndarmbiopsien entnommen und zur biochemischen, histochemischen und elektronenoptischen Auswertung entsprechend aufgearbeitet.

Die cellulare (mittels Migrations-inhibitionstest, MT) und humorale (mittels Immunfluorescenztechnik) Immunreaktion gegen Nebennieren-Antigene wurde bei 19 Patienten mit idiopathischer Nebennierenrindeninsuffizienz (INI) und 19 Kontrollpersonen untersucht. Bei 12 Patienten konnte eine ausgepragte Hemmung der Migration mononuclearer Zellen (MM) in Gegenwart von NN-Mikrosomen beobachtet werden; dagegen lag bei 18 der 19 Kontrollpersonen die MM im Normbereich. Zusatzlich konnten bei 11 (53%) der Patienten Nebennierenrinden-Antikorper (NNR-AK) festgestellt werden. In einer weiteren Untersuchungsreihe wurden NN-Mikrosomen mit NNR-AK vorinkubiert, im MT eingesetzt und die erhaltenen Migrationsindices mit denen durch NN-Mikrosomen allein erzielten verglichen. Bei 6 der 10 NNR-AK positiven Patienten konnte eine Hemmung der MM mit NN-Mikrosomen durch spezifische AK blockiert werden. Bei den NNR-AK negativen Patienten war kein einheitlicher Trend zu einer negativen oder positiven Beeinflussung der MM nachweisbar. Eine Blockierung der cellularen Immunreaktion durch spezifische Antikorper in diesem System erscheint wahrscheinlich. Mogliche Mechanismen, die dazu fuhren konnten, sowie die Bedeutung der NNR-AK werden diskutiert.

The binding of 125I-insulin to insulin receptors on circulating mononuclear leukocytes was studied in ten patients with hyperthyroidism and 20 euthyroid normal volunteers. The hyperthyroid patients demonstrated significantly elevated glucose levels following an oral glucose load, despite normal insulin secretion. The infusion of insulin resulted in a delayed hypoglycaemic effect in the hyperthyroid patients; however, the inhibition of the endogenous insulin secretion as indicated by suppression of C-peptide levels was not different from euthyroid control subjects. Insulin binding to monocytes was significantly decreased in the hyperthyroid patients. Scatchard analysis of binding data indicates that a decrease of receptor number rather than receptor affinity seems to be the cause of the lowered insulin binding in hyperthyroid patients with diffuse toxic goitre. The findings of decreased insulin receptor number, mild degree of glucose intolerance despite normal insulin secretion and the delayed hypoglycaemic effect following insulin infusion suggest that peripheral insulin resistance could be involved in the highly complex pathophysiology of glucose intolerance in hyperthyroidism.

In 9 newly diagnosed type I diabetic children the residual beta-cell secretory capacity was examined after stimulation with oral glucose load, glucagon and iv glucose plus arginine hydrochloride administration shortly after diagnosis and in the partial remission phase. A significant C-peptide secretion induced by these substances except by iv glucose was found at both investigation times. Whereas beta-cell function did only slightly increase from the initial testing to the measurements in the partial remission, beta-cell sensitivity increased significantly (p less than 0.05). The data suggest that "partial remission" referred to C-peptide secretion starts very early after insulin treatment and that other factors, possibly a decrease of peripheral insulin resistance, are involved in the improved metabolic control in partial remission phase.

In the present study insulin binding properties of human semi-synthetic and porcine insulin were compared in Type 1 (insulin-dependent) diabetic patients treated from the onset of their disease either with human semi-synthetic insulin (n = 12) or porcine insulin (n = 12) and control subjects (n = 12). In all three groups, insulin binding to circulating monocytes revealed no difference between human semi-synthetic and porcine insulin (specific insulin binding at tracer concentration: 5.7 +/- 0.5% versus 5.4 +/- 0.5% in control subjects, 5.5 +/- 0.4% versus 5.4 +/- 0.4% in Type 1 diabetic patients on porcine insulin, 5.3 +/- 0.4% versus 5.6 +/- 0.4% in Type 1 diabetic patients on human insulin). Treatment with human or porcine insulin did not have any significant influence on receptor binding properties of the two diabetic groups investigated. Absolute receptor number and affinity of both diabetic groups were within the range of healthy control subjects irrespective of treatment with human or porcine insulin.

Growth hormone levels following an intravenous bolus injection of 1 micrograms/kg body weight growth hormone releasing hormone were measured in 21 non-obese and 26 obese patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 13 control subjects. Growth hormone responses in non-obese Type 2 diabetic patients were not statistically different from control subjects. However, obese Type 2 diabetic patients had significantly decreased growth hormone responses to growth hormone releasing hormone when compared with non-obese Type 2 diabetic patients (p less than 0.02). In 9 Type 2 diabetic patients growth hormone releasing hormone tests were performed both during hyperglycaemia and after metabolic improvement by insulin treatment. Growth hormone responses before and after insulin treatment were not statistically different. Our data demonstrate that growth hormone responses to growth hormone releasing hormone in non-obese Type 2 diabetic patients do not differ significantly from control subjects; obesity blunts growth hormone responses to growth hormone releasing hormone in Type 2 diabetes mellitus; and growth hormone responses following growth hormone releasing hormone administration in Type 2 diabetes mellitus are not influenced by the state of metabolic control.

Bay m 1099 is a newly developed inhibitor of intestinal alpha-glucosidase. Its ability to lower postprandial plasma glucose, serum insulin and C-peptide levels in Type II diabetics has been investigated. Fifteen obese Type II diabetic patients with inadequate metabolic control during sulphonylurea treatment received a standardized diet and were treated either with Bay m 1099, b.d. (100 mg before breakfast and dinner) or placebo for 3 days, according to a double-blind cross-over design. The postprandial blood glucose level was significantly lower during Bay m 1099 treatment compared to placebo after breakfast and dinner (AUC after breakfast p less than 0.001). The reduced postprandial hyperglycaemia was associated with a decrease in meal stimulated serum insulin and C-peptide levels. Thus, Bay m 1099 may be a useful addition in the treatment of Type II diabetic patients.