The Anrep effect represents the alteration of left ventricular (LV) contractility to acutely enhanced afterload in a few seconds, thereby preserving stroke volume (SV) at constant preload. As a result of the missing preload stretch in our model, the Anrep effect differs from the slow force response and has a different mechanism. r The Anrep effect demonstrated two different phases. First, the sudden increased afterload was momentary equilibrated by the enhanced LV contractility as a result of higher power strokes of

During the COVID-19 pandemic, there were increased concerns about glycemic control in patients with diabetes. Therefore, we aimed to assess changes in diabetes management during the COVID-19 lockdown for patients with type 1 or type 2 diabetes mellitus (T1DM, T2DM) in Germany. We included data from 24,623 patients (age>18 years) with T1DM (N=6,975) or T2DM (N=17,648) with documented data in 2019 and 2020 from the multicenter Diabetes-Prospective Follow-up registry (DPV). We conducted a groupwise comparison of identical patients in 2019 and 2020 for different time periods of pandemia. Pairwise differences of continuous parameters of treatment modalities and metabolic outcome between 2019 and 2020 were adjusted for seasonality, age, and diabetes duration. We presented these outcomes as adjusted medians with 95% confidence intervals. Rates were compared using negative-binomial models, dichotomous outcomes were compared using logistic models. Models were additionally adjusted for age and diabetes duration. These outcomes were presented as least-square means with 95% confidence intervals, p-values of<.05 were considered significant.In participants with T1DM, CGI (combined glucose indicator) increased only by 0.11–0.12% in all time periods of 2020 compared to 2019 (all p<0.001) while BMI decreased slightly by −(0.09–0.10) kg/m² (p<0.0001). In participants with T2DM, HbA1c increased by 0.12%, while BMI decreased slightly by −(0.05–0.06) kg/m² (p<0.0001).During the COVID-19 lockdown period, patients with T1DM and T2DM experienced only clinically insignificant changes in glucose control or body weight. Despite lockdown restrictions, patients were able to maintain metabolic control.

Purpose About 20–25% of patients experience weight regain (WR) or insufficient weight loss (IWL) after bariatric metabolic surgery (BS). Therefore, we aimed to retrospectively assess the effectiveness of adjunct treatment with the GLP-1 receptor agonist semaglutide in non-diabetic patients with WR or IWL after BS. Materials and Methods Post-bariatric patients without type 2 diabetes (T2D) with WR or IWL (n = 44) were included in the analysis. The primary endpoint was weight loss 3 and 6 months after initiation of adjunct treatment. Secondary endpoints included change in BMI, HbA1c, lipid profile, hs-CRP, and liver enzymes. Results Patients started semaglutide 64.7 ± 47.6 months (mean ± SD) after BS. At initiation of semaglutide, WR after post-bariatric weight nadir was 12.3 ± 14.4% (mean ± SD). Total weight loss during semaglutide treatment was − 6.0 ± 4.3% (mean ± SD, p < 0.001) after 3 months (3.2 months, IQR 3.0–3.5, n = 38) and − 10.3 ± 5.5% (mean ± SD, p < 0.001) after 6 months (5.8 months, IQR 5.8–6.4, n = 20). At 3 months, categorical weight loss was > 5% in 61% of patients, > 10% in 16% of patients, and > 15% in 2% of patients. Triglycerides (OR = 0.99; p < 0.05), ALT (OR = 0.87; p = 0.05), and AST (OR = 0.89; p < 0.05) at baseline were negatively associated with weight loss of at least 5% at 3 months’ follow-up (p < 0.05). Conclusion Treatment options to manage post-bariatric excess weight (regain) are scarce. Our results imply a clear benefit of adjunct treatment with semaglutide in post-bariatric patients. However, these results need to be confirmed in a prospective randomized controlled trial to close the gap between lifestyle intervention and revision surgery in patients with IWL or WR after BS. Graphical abstract

Aim To assess the prevalence of elevated liver enzymes and associated diabetes‐related comorbidities in type 2 diabetes (T2D). Subjects and Methods Between 2010 and 2019, 281 245 patients with T2D (aged 18‐75 years) from 501 Diabetes Prospective Follow‐up (DPV) centres were evaluated, resulting in analysis of 51 645 patients with complete data on demographics and liver enzymes. Results Elevated liver enzymes were found in 40.2% of all patients. However, only 8.6% of these patients had International Classification of Diseases‐10 codes for nonalcoholic fatty liver disease and/or nonalcoholic steatohepatitis. Adjusted for age, sex, diabetes duration, body mass index and glycated haemoglobin, a higher prevalence of arterial hypertension (P < 0.0001), dyslipidaemia (P < 0.0001), peripheral artery disease (P = 0.0029), myocardial infarction (P = 0.0003), coronary artery disease (P = 0.0001), microalbuminuria (P < 0.0001) and chronic kidney disease (P < 0.0001) was seen in patients with elevated versus normal liver enzymes. The prevalence of elevated liver enzymes was lowest in patients receiving sodium‐glucose cotransporter‐2 (SGLT2) inhibitors or a combination of SGLT2 inhibitors and glucagon‐like peptide‐1 receptor agonists. Conclusion Elevated liver enzymes are common in patients with T2D and clearly correlate with a higher prevalence of clinically relevant comorbidities. Assessing liver enzymes should be standard clinical routine in T2D due to a possible predictive role for comorbidities and complications.

The ‘time-of-day’ modifies the metabolic response to meals, but less data exist on the diurnal variations in the hedonic drive to eat. In the present paper, we evaluate the effects of meal timing and macronutrient composition on metabolic responses and the homeostatic vs. hedonic regulation of appetite. In study 1, 84 young, healthy adults completed an online computer-based task assessing the homeostatic and hedonic drive to eat in the morning and evening. In study 2, 24 healthy, young men received 2 identical (850 kcal each) meals in the morning (8:45 h) and evening (18:00 h), of 2 experimental conditions: (i) regular carbohydrate (CH) meals (regular-CH), and (ii) high carbohydrate (high-CH) meals, containing 50 and 80% of energy from CHs, respectively. Serial blood samples were obtained, and the postprandial feelings of hunger, satiety, wanting and liking were assessed. Study 1 revealed a higher hedonic drive to eat in the evening compared to the morning. Study 2 confirmed this diurnal pattern of hedonic appetite regulation and, moreover, showed increased glucose and insulin responses to the evening meal. Postprandial ghrelin and leptin as well as feelings of hunger and satiety were not different between the mealtimes nor between the macronutrient conditions. In line with this, the homeostatic drive to eat was neither affected by the mealtime nor macronutrient composition. Increased the hedonic drive to eat in the evening may represent a vulnerability to palatable food and, thus, energy overconsumption. Together with lower evening glucose tolerance, these findings reflect an adverse metabolic constellation at the end of the day, especially after the ingestion of CH-rich foods.

Central insulin is critically involved in the regulation of hedonic feeding. Insulin resistance in overweight has recently been shown to reduce the inhibitory function of insulin in the human brain. How this relates to effective weight management is unclear, especially in older people, who are highly vulnerable to hyperinsulinemia and in whom neural target systems of insulin action undergo age-related changes. Here, 50 overweight, non-diabetic older adults participated in a double-blind, placebo-controlled, pharmacological functional magnetic resonance imaging study before and after randomization to a 3-month caloric restriction or active waiting group. Our data show that treatment outcome in dieters can be predicted by baseline measures of individual intranasal insulin (INI) inhibition of value signals in the ventral tegmental area related to sweet food liking as well as, independently, by peripheral insulin sensitivity. At follow-up, both INI inhibition of hedonic value signals in the nucleus accumbens and peripheral insulin sensitivity improved with weight loss. These data highlight the critical role of central insulin function in mesolimbic systems for weight management in humans and directly demonstrate that neural insulin function can be improved by weight loss even in older age, which may be essential for preventing metabolic disorders in later life.

ZusammenfassungMedikamentöse Therapiestrategien sind dringend erforderlich, um Adipositas-assoziierte Begleiterkrankungen langfristig reduzieren und verhindern zu können. Mit einer Gewichtsabnahme um 10% kann bereits eine Reduktion kardiovaskulärer Endpunkte erreicht werden. Als medikamentöse Therapieoption stehen aktuell in Deutschland der Lipaseinhibitor Orlistat sowie der GLP-1 Rezeptor-Agonist (GLP-1RA) Liraglutid zur medikamentösen Langzeittherapie der Adipositas zur Verfügung. Perspektivisch könnten zukünftig noch weitere Therapieoptionen zur Verfügung stehen, mit denen eine effektive Gewichtsreduktion erzielt werden kann. Semaglutid ist bereits als GLP-1RA zur Therapie des Typ 2 Diabetes zugelassen und zeigt, neben einer effektiven HbA1c-Senkung, eine deutliche Gewichtsreduktion. Im Fokus aktueller Adipositasforschung stehen zudem die Multi-Agonisten auf GLP-1-Basis, die balanziert an Rezeptoren mehrerer gastrointestinaler Peptide binden. So zeigen klinische Studien bspw. mit einem dualen Agonisten aus GLP1 und GIP (Glucose-dependent insulinotropic peptide) vielversprechende Körpergewichts-reduzierende Effekte. Weitere Forschungsansätze medikamentöser Therapieoptionen zur Gewichtsreduktion basieren u. a. auf Glukagon-Analoga, PYY und Amylin, aber auch auf Kombinationstherapien wie Leucin-Metformin-Sildenafil. Neben einer Verringerung der Nahrungsaufnahme werden derzeit zudem Therapieansätze zur Steigerung des Energieumsatzes, z. B. über die Aktivierung des braunen Fettgewebes, intensiv beforscht. In diesem Übersichtsartikel werden aktuelle sowie mögliche zukünftige Therapieoptionen zur Gewichtsreduktion in der Therapie der Adipositas zusammengefasst.

Obesity is a dramatically increasing disease, accompanied with comorbidities such as cardiovascular disease and obstructive sleep apnea syndrome (OSAS). Both obesity and OSAS per se are associated with systemic inflammation. However, the multifactorial impact of obesity, OSAS, and its concomitant diseases on the immunological characteristics of circulating monocytes has not yet been fully resolved. Monocyte subsets of 82 patients with obesity were analyzed in whole blood measurements in terms of the CD14/CD16 cell surface expression patterns and different monocytic adhesion molecules using flow cytometry. Plasma levels of adipokines adiponectin and leptin of all patients were evaluated and correlated with accompanying cellular and clinical values. Whole blood measurements revealed a significant overall redistribution of CD14/CD16 monocyte subsets in patients with obesity. Monocytic adhesion molecules CD11a, CD11b, and CX3CR1 were significantly elevated. The observed alterations significantly correlated with plasma leptin levels and diabetes status as crucial amplifying factors. The additive impact of obesity, diabetes, and OSAS on the immunological balance of peripheral blood monocytes requires a coordinated regimen in terms of therapeutic treatment, respiratory support, and weight loss to improve the systemic immunity in these patients.