Cardiovascular disease (CVD) is the most significant prognostic factor in individuals with type 2 diabetes (T2D). However, a significant number of individuals may develop CVD that does not present ...with the classic angina-related or heart failure symptoms. In these cases, CVD may seem to be 'silent' or 'asymptomatic', but may be more accurately characterised as unrecognised diabetic cardiac impairment. An initial step to raise awareness of unrecognised CVD in individuals with T2D would be to reach a consensus regarding the terminology used to describe this phenomenon. By standardising the terminologies, and agreeing on the implementation of an efficient screening program, it is anticipated that patients will receive an earlier diagnosis and appropriate and timely treatment. Given the availability of anti-diabetic medications that have been shown to concomitantly reduce CV risk and mortality, it is imperative to improve early identification and initiate treatment as soon as possible in order to enable as many patients with T2D as possible to benefit.
It is a matter of debate whether diabetes alone or its associated comorbidities are responsible for severe COVID-19 outcomes. This study assessed the impact of diabetes on intensive care unit (ICU) ...admission and in-hospital mortality in hospitalized COVID-19 patients.
A retrospective analysis was performed on a countrywide cohort of 40,632 COVID-19 patients hospitalized between March 2020 and March 2021. Data were provided by the Austrian data platform. The association of diabetes with outcomes was assessed using unmatched and propensity-score matched (PSM) logistic regression.
12.2% of patients had diabetes, 14.5% were admitted to the ICU, and 16.2% died in the hospital. Unmatched logistic regression analysis showed a significant association of diabetes (odds ratio OR: 1.24, 95% confidence interval CI: 1.15-1.34,
< 0.001) with in-hospital mortality, whereas PSM analysis showed no significant association of diabetes with in-hospital mortality (OR: 1.08, 95%CI: 0.97-1.19,
= 0.146). Diabetes was associated with higher odds of ICU admissions in both unmatched (OR: 1.36, 95%CI: 1.25-1.47,
< 0.001) and PSM analysis (OR: 1.15, 95%CI: 1.04-1.28,
= 0.009).
People with diabetes were more likely to be admitted to ICU compared to those without diabetes. However, advanced age and comorbidities rather than diabetes itself were associated with increased in-hospital mortality in COVID-19 patients.
OBJECTIVE: The increased cardiovascular risk in diabetes has been linked to endothelial and renal dysfunction. The aim of this study was to investigate the role of stable fragments of the precursors ...of adrenomedullin, endothelin-1, vasopressin, and atrial natriuretic peptide in progression of cardiovascular disease in patients with diabetes. RESEARCH DESIGN AND METHODS: This was a prospective, observational study design with a composite end point (death or unexpected admission to hospital due to a cardiovascular event) on 781 patients with type 2 diabetes (54 events, median duration of observation 15 months). The four stable precursor peptides midregional adrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), COOH-terminal proendothelin-1 (CT-proET-1), and COOH-terminal provasopressin or copeptin (CT-proAVP) were determined at baseline, and their association to renal function and cardiovascular events was studied using stepwise linear and Cox logistic regression analysis and receiver operating characteristic analysis, respectively. RESULTS: MR-proADM, CT-proET-1, CT-proAVP, and MR-proANP were all elevated in patients with future cardiovascular events and independently correlated to serum creatinine. MR-proADM and MR-proANP were significant predictors of a future cardiovascular event, with MR-proANP being the stronger (area under the curve 0.802 ± 0.034, sensitivity 0.833, specificity 0.576, positive predictive value 0.132, and negative predictive value 0.978 with a cutoff value of 75 pmol/l). CONCLUSIONS: The four serum markers of vasoactive and natriuretic peptides are related to both kidney function and cardiovascular events, thus linking two major complications of diabetes, diabetic nephropathy and cardiovascular disease.
1 Department of Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Austria; 2 Research Department, BRAHMS, Biotechnology Centre, Hennigsdorf, Germany; and 3 ...Department of Medicine II, Division of Cardiology, Medical University of Vienna, Austria
Submitted 24 March 2008
; accepted in final form 1 October 2008
Circulating levels of B-type natriuretic peptide (BNP) and NH 2 -terminal-proBNP (NT-proBNP) increase in response to volume overload and help in the differential diagnosis of acute heart failure. Elevated plasma BNP levels are observed also in sepsis and do not always correspond to left ventricular dysfunction. Here, we investigated plasma NT-proBNP fluctuations in response to human bacterial endotoxinemia, an experimental model of systemic infection and inflammation. Escherichia coli endotoxin (LPS) (2 ng/kg) was administered to 10 healthy volunteers in a randomized, placebo-controlled, cross-over design. Plasma NT-proBNP, C-reactive protein (CRP), COOH terminal pro-endothelin-1 (CT-proET-1), and midregional-pro-adrenomedullin (MR-proADM) were measured at hourly intervals for 6 h. LPS administration induced a continuous increase in plasma NT-proBNP that reached peak values after 6 h (40.7 ± 7.9 vs. 16.1 ± 3.2 pg/ml in placebo days, mean ± SE; P = 0.023). The profile of changes in NT-proBNP correlated to changes in body temperature ( P < 0.001), heart rate ( P = 0.005), CRP ( P < 0.001), and CT-proET-1 ( P = 0.008), but not to blood pressure values. Our results demonstrate that plasma NT-proBNP increases in a model of systemic infection/inflammation in healthy men with normal heart function. This finding emphasizes the necessity to consider concomitant infections when interpreting elevated circulating NT-proBNP concentrations.
B-type natriuretic peptide; C-reactive protein; bacterial endotoxin; infection; inflammation; human
Address for reprint requests and other correspondence: M. Clodi, Dept. of Medicine III, Medical Univ. of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria (e-mail: martin.clodi{at}meduniwien.ac.at )
Background
Recently, vaspin was identified as a novel adipokine with insulin-sensitizing effects that might be implicated in endogenous glucose regulation. Our objective was to evaluate the impact of ...acute weight loss and metabolic changes on serum vaspin concentrations in morbidly obese subjects following laparoscopic Roux-en-Y gastric bypass (RYGB) surgery.
Methods
Longitudinal, clinical intervention study in 33 morbidly obese subjects before and 12 months after RYGB was conducted. Fasting serum concentrations of vaspin were measured by a commercially available ELISA and correlated with BMI, parameters of insulin sensitivity, and other biochemical measurements. Fasting insulin sensitivity was estimated using the homeostasis model assessment (HOMA) of insulin resistance.
Results
RYGB-induced weight loss resulted in a reduction of circulating vaspin, leptin, insulin, and C-peptide levels as well as of BMI, HbA1c, and HOMA (
p
< 0.0001, respectively). Changes in serum vaspin concentrations correlated positively with those in HOMA, insulin, C-peptide, HbA1c, and leptin (
p
< 0.05, respectively) levels. The association between percent change of vaspin and HOMA remained significant even after the adjustment for RYGB-induced changes in BMI.
Conclusions
Following RYGB surgery, changes in serum vaspin concentrations correlate significantly with the reduction of circulating leptin, insulin, and C-peptide levels and with the amelioration of insulin sensitivity. However, further studies have to elucidate whether vaspin is only a biomarker for body-weight-related changes of insulin sensitivity or whether it is implicated in the regulation of human glucose homeostasis.
•Head-to-head comparison of the fully-automated Elecsys® Anti-SARS-CoV-2.•With the EDITM IgM and IgG ELISAs for the detection of SARS-CoV-2 antibodies.•Antibodies were measured in COVID-19 patients, ...healthy blood donors and ICU patients.•Our findings indicate very high sensitivity/specificity for the Anti-SARS-CoV-2 assay.•We found acceptable agreement with the EDITM IgM and IgG ELISAs.
Here, we report on a head-to-head comparison of the fully-automated Elecsys® Anti-SARS-CoV-2 immunoassay with the EDITM enzyme linked immunosorbent assays (ELISA) for the detection of SARS-CoV-2 antibodies in human plasma.
SARS-CoV-2 antibodies were measured with the Elecsys® assay and the EDITM ELISAs (IgM and IgG) in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n = 104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used.
In COVID-19 patients, the percentage of positive results rose with time from symptom onset, peaking to positivity rates after 15–22 days of 100% for the Elecsys® assay, of 94% for the EDITM IgM-ELISA and of 100% for the EDITM IgG ELISA. In the 104 blood samples, the agreement between positive/negative classifications of the Elecsys® assay and the EDITM ELISAs (IgM or IgG) was 90%. The false positivity rates in the healthy blood donors and the ICU patients were < 1% for the Elecsys® assay and < 3% for the EDITM ELISAs.
Our results indicate a high sensitivity and specificity for the Elecsys® assay and an acceptable agreement with the EDITM ELISAs.
Oxytocin (OXT) and ghrelin have several common properties such as the involvement in the first phase response to stressors, in appetite regulation, and in the modulation of neural functions. Despite ...a recent study showing that intraventricular administration of ghrelin activates OXT neurons, little is known on the cross-talk between these two peptides. Here, we investigated the role of the i.v. administration of OXT on circulating ghrelin concentrations under fasting conditions and during the lipopolysaccharide (LPS)-induced endotoxemia. A randomized placebo-controlled cross-over study was performed in ten healthy men. In four study sessions, the participants received once placebo, once OXT (1 pmol/kg per min over 90 min), once LPS (2 ng/kg), and once both OXT and LPS. Plasma ghrelin, glucose, and free fatty acid (FFA) levels were measured at regular intervals during the first 6 h following the LPS bolus. Systemic administration of OXT decreased within 1 h plasma ghrelin levels (611±54 vs 697±52 pg/ml in placebo days, P=0.013) and increased plasma glucose and FFA concentrations (P=0.002 and P=0.005 respectively). OXT also reduced the LPS-induced surge in ghrelin at time point 2 h (P=0.021). In , i.v. administration of OXT decreases circulating levels of ghrelin during fasting, as well as following LPS-induced endotoxemia in healthy men. The cross-talk between OXT and ghrelin might be important in the regulation of energy homeostasis and stress responses.
Cholinergic Regulation of Ghrelin and Peptide YY Release May Be Impaired in Obesity
Christina Maier 1 ,
Michaela Riedl 1 ,
Greisa Vila 1 ,
Peter Nowotny 1 ,
Michael Wolzt 2 ,
Martin Clodi 1 ,
...Bernhard Ludvik 1 and
Anton Luger 1
1 Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
2 Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
Corresponding author: Christina Maier, christina.maier{at}meduniwien.ac.at
Abstract
OBJECTIVE— Ghrelin and peptide YY (PYY) are both hormones derived from the gastrointestinal tract involved in appetite regulation. The
cholinergic part of the vagal nerve is involved in the regulation of glucose and insulin. The aim of this study was to examine
the effects of the cholinergic antagonist atropine on ghrelin, PYY, glucose, and insulin under basal conditions and after
meal ingestion in lean and obese subjects.
REASEARCH DESIGN AND METHODS— Eight lean and eight obese subjects were included in a randomized, double-blind, placebo-controlled crossover study with 4
study days in randomized order (atropine/placebo ± breakfast). Plasma ghrelin, PYY, insulin, and glucose were measured. Hunger
and satiety feelings were rated on a 10-cm visual analog scale.
RESULTS— In lean individuals, atropine led to a decrease in ghrelin concentrations comparable and nonadditive with breakfast ingestion
and a significant decrease in both basal and meal-induced PYY concentrations. In obese subjects, atropine did not significantly
change ghrelin or PYY concentrations, whereas it induced a comparable increase in heart rate and meal-induced glucose concentrations
in the two study groups. Only lean, not obese, subjects experienced sustained feelings of satiety after breakfast.
CONCLUSIONS— The impaired cholinergic regulation of the postprandial drop in ghrelin concentrations and rise in PYY concentrations might
be part of the deregulated food intake in obese subjects.
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 20 June 2008.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted June 17, 2008.
Received June 4, 2007.
DIABETES
Adrenomedullin (ADM) is a vasoactive peptide found to be related to obesity and its comorbidities: type 2 diabetes, hypertension, atherosclerosis, and coronary heart disease. ADM is increased both in ...plasma and in adipose tissue of obese individuals when compared to lean subjects and is considered as a member of the adipokine family. We determined plasma midregional proadrenomedullin (MR‐proADM) concentrations in a cohort of 357 subjects with BMI ranging from 17.5 to 42.3 kg/m2 and no additional medical history. In parallel, 28 severely obese patients scheduled to undergo laparoscopic Roux‐en‐Y gastric bypass (RYGB) surgery were studied at two time points: before and 1 year after surgery. Outcome measurements were: MR‐proADM, cortisol, leptin, C‐reactive protein (CRP) thyroid‐stimulating hormone (TSH), creatinine and metabolic parameters. BMI correlated significantly to plasma MR‐proADM levels (r = 0.714, P < 0.001), also after adjustment for age and gender (r = 0.767, P < 0.001). In obese subjects, there was a positive relationship between MR‐proADM and leptin (r = 0.511, P = 0.006). Following RYGB, plasma MR‐proADM decreased from 0.76 ± 0.03 to 0.62 ± 0.02 pg/ml (P < 0.0001). RYGB‐induced changes in MR‐proADM correlated significantly to changes in leptin (r = 0.533, P = 0.004) and in CRP (r = 0.429, P = 0.023). We conclude that BMI is an independent predictor of circulating MR‐proADM levels. Weight loss after RYGB is associated with a significant decrease in plasma MR‐proADM, which is related to surgery‐induced changes in both circulating leptin and systemic inflammation.
The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro-B-type natriuretic peptide (NT-proBNP).
Few clinical trials ...have successfully demonstrated the prevention of cardiac events in patients with diabetes. One reason for this might be an inaccurate selection of patients. NT-proBNP has not been assessed in this context.
A total of 300 patients with type 2 diabetes, elevated NT-proBNP (>125 pg/ml) but free of cardiac disease were randomized. The "control" group was cared for at 4 diabetes care units; the "intensified" group was additionally treated at a cardiac outpatient clinic for the up-titration of renin-angiotensin system (RAS) antagonists and beta-blockers. The primary endpoint was hospitalization/death due to cardiac disease after 2 years.
At baseline, the mean age of the patients was 67.5 ± 9 years, duration of diabetes was 15 ± 12 years, 37% were male, HbA1c was 7 ± 1.1%, blood pressure was 151 ± 22 mm Hg, heart rate was 72 ± 11 beats/min, median NT-proBNP was 265.5 pg/ml (interquartile range: 180.8 to 401.8 pg/ml). After 12 months there was a significant difference between the number of patients treated with a RAS antagonist/beta-blocker and the dosage reached between groups (p < 0.0001). Blood pressure was significantly reduced in both (p < 0.05); heart rate was only reduced in the intensified group (p = 0.004). A significant reduction of the primary endpoint (hazard ratio: 0.351; 95% confidence interval: 0.127 to 0.975, p = 0.044) was visible in the intensified group. The same was true for other endpoints: all-cause hospitalization, unplanned cardiovascular hospitalizations/death (p < 0.05 for all).
Accelerated up-titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP. (Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients PONTIAC; NCT00562952).
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