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Complications of diabetes are often attributed to glucose and reactive dicarbonyl metabolites derived from glycolysis or gluconeogenesis, such as methylglyoxal. However, in the CNS, neurons and endothelial cells use lactate as energy source in addition to glucose, which does not lead to the formation of methylglyoxal and has previously been considered a safer route of energy consumption than glycolysis. Nevertheless, neurons and endothelial cells are hotspots for the cellular pathology underlying neurological complications in diabetes, suggesting a cause that is distinct from other diabetes complications and independent of methylglyoxal. Here, we show that in clinical and experimental diabetes plasma concentrations of dimethylglyoxal are increased. In a mouse model of diabetes, ilvb acetolactate-synthase-like (ILVBL, HACL2) is the enzyme involved in formation of increased amounts of dimethylglyoxal from lactate-derived pyruvate. Dimethylglyoxal reacts with lysine residues, forms Nε−3-hydroxy-2-butanonelysine (HBL) as an adduct, induces oxidative stress more strongly than other dicarbonyls, causes blood-brain barrier disruption, and can mimic mild cognitive impairment in experimental diabetes. These data suggest dimethylglyoxal formation as a pathway leading to neurological complications in diabetes that is distinct from other complications. Importantly, dimethylglyoxal formation can be reduced using genetic, pharmacological and dietary interventions, offering new strategies for preventing CNS dysfunction in diabetes. Diabetes complications are attributed to reactive by-products of glycolysis, but cells consuming lactate and pyruvate are not spared. Here, the authors show that the reactive dicarbonyl dimethylglyoxal is formed from pyruvate, rises in diabetes, and potentially causes neurological complications of diabetes. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea syndrome (OSAS) and obesity go hand in hand in the majority of patients and both are associated with a systemic inflammation, immune disturbance and comorbidities such as cardiovascular disease. However, the unambiguous impact of OSAS and obesity on the individual inflammatory microenvironment and the immunological consequences of human monocytes has not been distinguished yet. Therefore, aim of this study was to investigate the impact of OSAS and obesity related factors on the inflammatory microenvironment by performing flow cytometric whole blood measurements of CD14/CD16 monocyte subsets in normal weight OSAS patients, patients with obesity but without OSAS, and patients with OSAS and obesity, compared to healthy donors. Moreover, explicitly OSAS and obesity related plasma levels of inflammatory mediators adiponectin, leptin, lipocalin and metalloproteinase-9 were determined and the influence of different OSAS and obesity related factors on cytokine secretion and expression of different adhesion molecules by THP-1 monocytes was analysed. Our data revealed a significant redistribution of circulating classical and intermediate monocytes in all three patient cohorts, but differential effects in terms of monocytic adhesion molecules CD11a, CD11b, CD11c, CX3CR1, CD29, CD49d, and plasma cytokine levels. These data were reflected by differential effects of OSAS and obesity related factors leptin, TNFα and hypoxia on THP-1 cytokine secretion patterns and expression of adhesion molecules CD11b and CD49d. In summary, our data revealed differential effects of OSAS and obesity, which underlines the need for a customized therapeutic regimen with respect to the individual weighting of these overlapping diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Attenuated counterregulation after recurrent hypoglycaemia is a major complication of diabetes treatment. As there is previous evidence for the relevance of sleep in metabolic control, we assessed the acute contribution of sleep to the counterregulatory adaptation to recurrent hypoglycaemia. Methods: Within a balanced crossover design, 15 healthy, normal-weight male participants aged 18–35 years underwent three hyperinsulinaemic–hypoglycaemic clamps with a glucose nadir of 2.5 mmol/l, under two experimental conditions, sleep and sleep deprivation. Participants were exposed to two hypoglycaemic episodes, followed by a third hypoglycaemic clamp after one night of regular 8 h sleep vs sleep deprivation. The counterregulatory response of relevant hormones (glucagon, growth hormone [GH], ACTH, cortisol, adrenaline [epinephrine] and noradrenaline [norepinephrine]) was measured, and autonomic and neuroglycopenic symptoms were assessed. Results: Sleep deprivation compared with sleep dampened the adaptation to recurrent hypoglycaemia for adrenaline (p=0.004), and this pattern also emerged in an overall analysis including adrenaline, GH and glucagon (p=0.064). After regular sleep, the counterregulatory responses of adrenaline (p=0.005), GH (p=0.029) and glucagon (p=0.009) were attenuated during the 3rd clamp compared with the 1st clamp, but were preserved after sleep deprivation (all p>0.225). Neuroglycopenic and autonomic symptoms during the 3rd clamp compared with the 1st clamp were likewise reduced after sleep (p=0.005 and p=0.019, respectively). In sleep deprivation, neuroglycopenic symptoms increased (p=0.014) and autonomic symptoms were unchanged (p=0.859). Conclusions/interpretation: The counterregulatory adaptation to recurrent hypoglycaemia is compromised by sleep deprivation between hypoglycaemic episodes, indicating that sleep is essential for the formation of a neurometabolic memory, and may be a potential target of interventions to treat hypoglycaemia unawareness syndrome. [ABSTRACT FROM AUTHOR]

Hintergrund: Die Prävalenz der Adipositas ist in den letzten Jahren stetig angestiegen. Adipositas stellt als chronische Krankheit weltweit ein Gesundheitsproblem dar und ist mit einer Vielzahl von Komorbiditäten wie beispielsweise Typ 2 Diabetes mellitus assoziiert.Ziel der Arbeit: Die vorliegende Arbeit gibt eine Übersicht über die Möglichkeiten und Grenzen der konservativen Therapie bei Adipositas. Zudem werden die Ursachen für die Adipositasentwicklung und die Assoziation von Adipositas und schlafbezogenen Atmungsstörungen (SBAS) erläutert.Material und Methoden: Es wurde Literatur zusammengefasst, die sich der konservativen Adipositastherapie in Form von Ernährungs‑, Bewegungs- und Verhaltenstherapie sowie medikamentöser Therapie widmet. Zudem wurde eine Vielzahl von experimentellen Studien zitiert, welche Grundlagenwissen in diesem Themenbereich liefern.Ergebnisse und Diskussion: Aufgrund der Komplexität der Pathogenese der Adipositas muss konservative Adipositastherapie auf einem multifaktoriellen Ansatz bestehen. Die Grundbausteine sind eine Ernährungs‑, Bewegungs- und Verhaltenstherapie. Bei nicht ausreichender Gewichtsreduktion kann eine zusätzliche medikamentöse Therapie indiziert sein. [ABSTRACT FROM AUTHOR]