Early and longer term effects of gastric bypass surgery on tissue-specific insulin sensitivity and beta cell function in morbidly obese patients with and without type 2 diabetes

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Renal perfusion, oxygenation and metabolism: the role of imaging

Thanks to technical advances in the field of medical imaging, it is now possible to study key features of renal anatomy and physiology, but so far poorly explored due to the inherent difficulties in studying both the metabolism and vasculature of the human kidney. In this narrative review, we provide an overview of recent research findings on renal perfusion, oxygenation, and substrate uptake. Most studies evaluating renal perfusion with positron emission tomography (PET) have been performed in healthy controls, and specific target populations like obese individuals or patients with renovascular disease and chronic kidney disease (CKD) have rarely been assessed. Functional magnetic resonance (fMRI) has also been used to study renal perfusion in CKD patients, and recent studies have addressed the kidney hemodynamic effects of therapeutic agents such as glucagon-like receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) in an attempt to characterise the mechanisms leading to their nephroprotective effects. The few available studies on renal substrate uptake are discussed. In the near future, these imaging modalities will hopefully become widely available with researchers more acquainted with them, gaining insights into the complex renal pathophysiology in acute and chronic diseases

Renal hemodynamics and fatty acid uptake: effects of obesity and weight loss

Human studies of renal hemodynamics and metabolism in obesity are insufficient. We hypothesized that renal perfusion and renal free fatty acid (FFA) uptake are higher in subjects with morbid obesity compared with lean subjects and that they both decrease after bariatric surgery. Cortical and medullary hemodynamics and metabolism were measured in 23 morbidly obese women and 15 age- and sex-matched nonobese controls by PET scanning of [O-15]-H2O (perfusion) and 14(R,S)-[F-18]fluoro-6-thia-heptadecanoate (FFA uptake). Kidney volume and radiodensity were measured by computed tomography, cardiac output by MRI. Obese subjects were re-studied 6 mo after bariatric surgery. Obese subjects had higher renal volume but lower radiodensity, suggesting accumulation of water and/or lipid. Both cardiac output and estimated glomerular filtration rate (eGFR) were increased by similar to 25% in the obese. Total renal blood flow was higher in the obese [885 (317) (expressed as median and interquartile range) vs. 749 (300) (expressed as means and SD) ml/min of controls, P = 0.049]. In both groups, regional blood perfusion was higher in the cortex than medulla; in either region, FFA uptake was similar to 50% higher in the obese as a consequence of higher circulating FFA levels. Following weight loss (26 +/- 8 kg), total renal blood flow was reduced (P = 0.006). Renal volume, eGFR, cortical and medullary FFA uptake were decreased but not fully normalized. Obesity is associated with renal structural, hemodynamic, and metabolic changes. Six months after bariatric surgery, the hemodynamic changes are reversed and the structural changes are improved. On the contrary, renal FFA uptake remains increased, driven by high substrate availability

The utilization of positron emission tomography in the evaluation of renal health and disease

PurposePositron emission tomography (PET) is a nuclear imaging technique that uses radiotracers to visualize metabolic processes of interest across different organs, to diagnose and manage diseases, and monitor therapeutic response. This systematic review aimed to characterize the value of PET for the assessment of renal metabolism and function in subjects with non-oncological metabolic disorders.MethodsThis review was conducted and reported in accordance with the PRISMA statement. Research articles reporting “kidney” or “renal” metabolism evaluated with PET imaging between 1980 and 2021 were systematically searched in Medline/PubMed, Science Direct, and the Cochrane Library. Search results were exported and stored in RefWorks, the duplicates were removed, and eligible studies were identified, evaluated, and summarized.ResultsThirty reports met the inclusion criteria. The majority of the studies were prospective (73.33%, n = 22) in nature. The most utilized PET radiotracers were 15O-labeled radio water (H215O, n = 14) and 18F-fluorodeoxyglucose (18F-FDG, n = 8). Other radiotracers used in at least one study were 14(R,S)-(18)F-fluoro-6-thia-heptadecanoic acid (18F-FTHA), 18F-Sodium Fluoride (18F-NaF), 11C-acetate, 68-Gallium (68Ga), 13N-ammonia (13N-NH3), Rubidium-82 (82Rb), radiolabeled cationic ferritin (RadioCF), 11C‐para-aminobenzoic acid (11C-PABA), Gallium-68 pentixafor (68Ga-Pentixafor), 2-deoxy-2-F-fluoro-D-sorbitol (F-FDS) and 55Co-ethylene diamine tetra acetic acid (55Co-EDTA).ConclusionPET imaging provides an effective modality for evaluating a range of metabolic functions including glucose and fatty acid uptake, oxygen consumption and renal perfusion. Multiple positron emitting radiolabeled racers can be used for renal imaging in clinical settings. PET imaging thus holds the potential to improve the diagnosis of renal disorders, and to monitor disease progression and treatment response.</p

Body Weight, Not Insulin Sensitivity or Secretion, May Predict Spontaneous Weight Changes in Nondiabetic and Prediabetic Subjects: The RISC Study

Previous studies have found that high insulin sensitivity predicts weight gain; this association has not been confirmed. Our aim was to systematically analyze metabolic predictors of spontaneous weight changes

Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery

Background and aims: Computed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients. Methods and results: We examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r =-0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radio density remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r =-0.66, p = 0.002).Conclusion: Higher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity. Clinical trial registration number: NCT01373892. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V

Circulating N-Acetylaspartate does not track brain NAA concentrations, cognitive function or features of small vessel disease in humans

N-acetylaspartate (NAA) is the second most abundant metabolite in the human brain; although it is assumed to be a proxy for a neuronal marker, its function is not fully elucidated. NAA is also detectable in plasma, but its relation to cerebral NAA levels, cognitive performance, or features of cerebral disease has not been investigated. To study whether circulating NAA tracks cerebral NAA levels, and whether circulating NAA correlates with cognitive function and features of cerebral small vessel disease (SVD). Two datasets were analyzed. In dataset 1, structural MRI was acquired in 533 subjects to assess four features of cerebral SVD. Cognitive function was evaluated with standardized test scores (N = 824). In dataset 2, brain H-1-MRS from the occipital region was acquired (N = 49). In all subjects, fasting circulating NAA was measured with mass spectrometry. Dataset 1: in univariate and adjusted for confounders models, we found no correlation between circulating NAA and the examined features of cerebral SVD. In univariate analysis, circulating NAA levels were associated inversely with the speed in information processing and the executive function score, however these associations were lost after accounting for confounders. In line with the negative findings of dataset 1, in dataset 2 there was no correlation between circulating and central NAA or total NAA levels. This study indicates that circulating NAA levels do not reflect central (occipital) NAA levels, cognitive function, or cerebral small vessel disease in man

The Role of Vitamin D in Health and Disease: A Narrative Review on the Mechanisms Linking Vitamin D with Disease and the Effects of Supplementation

Vitamin D insufficiency or deficiency (VDD) is a very prevalent condition in the general population. Vitamin D is necessary for optimal bone mineralization, but apart from the bone effects, preclinical and observational studies have suggested that vitamin D may have pleiotropic actions, whereas VDD has been linked to several diseases and higher all-cause mortality. Thus, supplementing vitamin D has been considered a safe and inexpensive approach to generate better health outcomes—and especially so in frail populations. Whereas it is generally accepted that prescribing of vitamin D in VDD subjects has demonstrable health benefits, most randomized clinical trials, although with design constraints, assessing the effects of vitamin D supplementation on a variety of diseases have failed to demonstrate any positive effects of vitamin D supplementation. In this narrative review, we first describe mechanisms through which vitamin D may exert an important role in the pathophysiology of the discussed disorder, and then provide studies that have addressed the impact of VDD and of vitamin D supplementation on each disorder, focusing especially on randomized clinical trials and meta-analyses. Despite there already being vast literature on the pleiotropic actions of vitamin D, future research approaches that consider and circumvent the inherent difficulties in studying the effects of vitamin D supplementation on health outcomes are needed to assess the potential beneficial effects of vitamin D. The evaluation of the whole vitamin D endocrine system, rather than only of 25-hydroxyvitamin D levels before and after treatment, use of adequate and physiologic vitamin D dosing, grouping based on the achieved vitamin D levels rather than the amount of vitamin D supplementation subjects may receive, and sufficiently long follow-up are some of the aspects that need to be carefully considered in future studies. © 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG

Near-Infrared Spectroscopy: A Free-Living Neuroscience Tool to Better Understand Diabetes and Obesity

The human brain is the least accessible of all organs and attempts to study it in vivo rely predominantly on neuroimaging. Functional near-infrared spectroscopy (fNIRS) allows for the study of cortical neural activity in a non-invasive manner that may resemble free-living conditions. Moreover, compared to other neuroimaging tools, fNIRS is less expensive, it does not require the use of ionizing radiation, and can be applied to all study populations (patients suffering from claustrophobia, or neonates). In this narrative review, we provide an overview of the available research performed using fNIRS in patients with diabetes and obesity. The few studies conducted to date have presented controversial results regarding patients with diabetes, some reporting a greater hemodynamic response and others reporting a reduced hemodynamic response compared to the controls, with an unclear distinction between types 1 and 2. Subjects with obesity or a binge eating disorder have reduced prefrontal activation in response to inhibitory food or non-food stimuli; however, following an intervention, such as cognitive treatment, prefrontal activation is restored. Moreover, we discuss the potential of future applications of fNIRS for a better understanding of cortical neural activity in the context of metabolic disorders