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Objective: One proposed mechanism of disease progression in Parkinson's disease includes the interplay of endogenous dopamine toxicity and mitochondrial dysfunction. However, the in‐vivo effects of exogenous dopamine administration on cerebral bioenergetics are unknown. Methods: We performed a double‐blinded, cross‐over, placebo‐controlled trial. Participants received either 200/50 mg levodopa/benserazide or a placebo and vice versa on the second study visit. Clinical assessments and multimodal neuroimaging were performed, including 31phosphorus magnetic resonance spectroscopy of the basal ganglia and the midbrain. Results: In total, 20 (6 female) patients with Parkinson's disease and 22 sex‐ and age‐matched healthy controls (10 female) were enrolled. Treatment with levodopa/benserazide but not with placebo resulted in a substantial reduction of high‐energy phosphorus‐containing metabolites in the basal ganglia (patients with Parkinson's disease: −40%; healthy controls: −39%) but not in the midbrain. There were no differences in high‐energy phosphorus‐containing metabolites for patients with Parkinson's disease compared to healthy controls in the OFF state and treatment response. Interpretation: Exogenously administered levodopa/benserazide strongly interferes with basal ganglia high‐energy phosphorus‐containing metabolite levels in both groups. The lack of effects on midbrain levels suggests that the observed changes are limited to the site of dopamine action. ANN NEUROL 2024;95:849–857 [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes is reaching epidemic proportions. First line therapy approaches are lifestyle interventions including exercise. Although a vast amount of studies reports on beneficial effects of exercise on metabolism in humans per se, overall data are contradictory which makes it difficult to optimize interventions. Innovative exercise strategies and its underlying mechanism are needed to elucidate in order to close this therapeutic gap. The skeletal muscle produces and secretes myokines and microRNAs in response to exercise and both are discussed as mechanisms linking exercise and metabolic adaptation. Aspects of chronophysiology such as diurnal variation in insulin sensitivity or exercise as a signal to reset dysregulated peripheral clocks are of growing interest in the context of impaired metabolism. Deep insight of how exercise timing determines metabolic adaptations is required to optimize exercise interventions. This review aims to summarize the current state of research on the interaction between timing of exercise and metabolism in humans, providing insights into proposed mechanistic concepts focusing on myokines and microRNAs. First evidence points to an impact of timing of exercise on health outcome, although data are inconclusive. Underlying mechanisms remain elusive. It is currently unknown if the timed release of mykokines depends on time of day when exercise is performed. microRNAs have been found as an important mediator of processes associated with exercise adaptation. Further research is needed to evaluate their full relevance. In conclusion, it seems to be too early to provide concrete recommendations on timing of exercise to maximize beneficial effects. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the newly developed non‐invasive blood glucose system NIRLUS® (Near‐Infra Red Light Ultra Sound; NIRLUS Engineering AG, Lübeck, Germany) under standardized conditions. Seventeen healthy men of normal weight (body mass index 22.4 ± 1.4 kg/m2), aged 18 to 45 years, were enrolled in this study. During an intravenous glucose tolerance test, blood glucose profiles were measured simultaneously using the NIRLUS system and a "gold standard" laboratory reference system. Correlation analysis revealed a strong association between NIRLUS and reference values (r = 0.934; P < 0.001). Subsequent Bland–Altman analysis showed a symmetric distribution (r = 0.047; P = 0.395), and 95.5% of the NIRLUS–reference pairs were within the difference (d) of d ± 2 SD. The median deviation of all paired NIRLUS–reference values was 0.5 mmol/L and the mean percent deviation was 11.5%. Error grid analysis showed that 93.6% of NIRLUS–reference pairs are located in the area A, and 6.4% in the area B. No data were allocated in the areas C to E. This proof‐of‐concept study demonstrates the reproducibility of accurate blood glucose measures obtained by NIRLUS as compared to a gold standard laboratory reference system. The technology of NIRLUS is an important step forward in the development of non‐invasive glucose monitoring. [ABSTRACT FROM AUTHOR]

Objective: Asian studies have reported on an association of Helicobacter pylori (Hp) infection with insulin resistance (IR) in normal-weight subjects. Whether such an association likewise exists in European subjects with severe obesity was questioned. Design and Methods: To address this question, 370 severely obese patients from our database were identified, who had undergone a gastroscopy with a histological examination of gastric mucosal biopsies and a concurrent assessment metabolic blood parameters as a standard examination before bariatric surgery. Results: Seventy-five (20.3%) of the subjects displayed a histologically proven Hp infection (Hp+). Sex distribution, age, and body mass index of Hp+ subjects did not differ from that of the subjects with no Hp infection (Hp-; all P > 0.293), but Hp+ subjects were significantly smaller ( P = 0.006). Fasting glucose, insulin, high-sensitive C reactive protein, and alanine aminotransferase levels as well as calculated indices of IR (i.e., HOMA-IR, QUICKI) did not differ between Hp+ and Hp- subjects (all P > 0.42). However, Hp+ subjects showed significantly higher triglyceride levels and a higher total chloesterol-to-HDL ratio but lower sex-hormone binding globulin (SHGB) levels than Hp- subjects (all P ≤ 0.05). Conclusion: While our results obtained in European severely obese patients do not provide evidence for an enhanced IR state associated with gastric Hp infection, they suggest that the presence of the bacterium in gastric biopsies is associated with an adverse lipid profile and reduced SHGB levels. [ABSTRACT FROM AUTHOR]

Summary: This systematic review investigated the effects of deep brain stimulation of the subthalamic nucleus on extent and time course of body mass changes in patients with Parkinson's disease. A computerized search identified relevant articles using a priori defined inclusion and exclusion criteria. A descriptive analysis was calculated for the main outcome parameters body mass and BMI. Thirty‐eight out of 206 studies fulfilled the inclusion criteria (979 patients aged 59.0±7.5 years). Considering the longest follow‐up time for each study, body mass and BMI showed a mean increase across studies of +5.71kg (p <.0001; d = 0.64) and +1.8kg/m2 (p <.0001; d = 1.61). The time course of body mass gain revealed a continuous increase ranging from +3.25kg (d = 0.69) at 3 months, +3.88kg (d = 0.21) at 6 months, +6.35kg (d = 0.72) at 12 months, and +6.11kg (d = 1.02) greater than 12 months. Changes in BMI were associated with changes in disease severity (r = 0.502, p =.010) and pharmacological treatment (r = 0.440, p =.0231). Data suggest that body mass gain is one of the most common side effects of deep brain stimulation going beyond normalization of preoperative weight loss. Considering the negative health implications of overweight, we recommend the development of tailored therapies to prevent overweight and associated metabolic disorders following this treatment. [ABSTRACT FROM AUTHOR]

Upper airway stimulation is a new and effective second‐line treatment for obstructive sleep apnea, but possible consequences on glucose metabolism and central regulation of food intake are unclear. Twenty patients were prospectively studied before and 12 months after obstructive sleep apnea treatment by upper airway stimulation. Respiratory parameters and daytime sleepiness were assessed to document effectiveness of treatment. Glucose metabolism was assessed by the oral glucose tolerance test, and hedonic versus homeostatic drive to eat was characterized. At 12 months, upper airway stimulation significantly improved measures of obstructive sleep apnea (all p < 0.01). Despite no change in body weight, fasting C‐peptide insulin resistance index (p = 0.01) as well as insulin and C‐peptide levels at 60 min during the oral glucose tolerance test (p < 0.02) were reduced. Hedonic drive to eat was strongly reduced (p < 0.05), while leptin and ghrelin remained unchanged (p > 0.15). Upper airway stimulation is effective in treatment of obstructive sleep apnea and improves glucose metabolism. Reduced hedonic drive to eat might contribute to these metabolic improvements. These promising findings are in need for long‐term controlled evaluation of metabolic sequelae of upper airway stimulation and to mechanistically evaluate the metabolic benefits of upper airway stimulation in patients with obstructive sleep apnea. [ABSTRACT FROM AUTHOR]