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Purpose

We aimed to characterize the RYGB-induced changes in the dynamics of brain glucose uptake. We addressed heterogeneity between brain regions during experimental normo- and hypoglycemia and explored associations with anthropometric and metabolic outcomes of RYGB.

Methods

Analyses of regional brain glucose uptake were performed on 9 individuals with obesity and no diabetes, investigated with combined brain ¹⁸F-FDG-PET and fMRI during hyperinsulinemic normo- and hypoglycemic clamp, one month before and four months after RYGB. FDG clearance, reflecting glucose uptake rate, was assessed in 38 brain regions, covering all cortical areas and subcortical nuclei, during hyperinsulinemic normo- and hypoglycemia. Correlation analyses were performed to identify associations with other outcomes of RYGB.

Results

FDG uptake rate during hypoglycemia was higher than during normoglycemia in all brain regions, both before and after RYGB. Moreover, in most regions and especially in cortical areas involved in inhibitory behavioral control, FDG uptake rate tended to be reduced after surgery during normoglycemia but elevated during hypoglycemia. However, these post-surgical changes in FDG uptake rate were opposite in the hypothalamus. Thus, the hypo-to-normoglycemia FDG clearance ratio tended to increase in all brain regions following RYGB, but not in the amygdala and the hypothalamus. Changes in regional FDG uptake rate after RYGB during normoglycemia were associated with weight loss and improved systemic insulin sensitivity.

Conclusion

Using dynamic FDG-PET, we show region-specific patterns of changes in glucose utilization following RYGB. In the hypothalamus, glucose uptake during normoglycemia tended to rise after RYGB while it was reduced in cortical regions involved in behavioral control. Following RYGB, the hypothalamus and amygdala, in contrast to other regions, displayed trends of reduced glucose uptake during hypoglycemia. These pilot results highlight the brain effects of RYGB and suggest behavioral and neuroendocrine adaptations which contribute to its antidiabetic effects.

Aims/hypothesis

Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes.

Methods

In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic–euglycaemic clamps during which concomitant simultaneous whole-body [18F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change.

Results

One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: −7.7±1.4 kg and −7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (−26.3% [95% CI −49.5, −3.0], p=0.009) and non-significantly following LCD (−20.9% [95% CI −58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected.

Conclusions/interpretation

The short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks.

Aims/hypothesis

Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investi-gate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet lowin energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the globaland tissue-specific level in individuals with obesity but not diabetes.

Methods

In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding,sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery(n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTTand hyperinsulinaemic–euglycaemic clamps during which concomitant simultaneous whole-body [ 18 F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change.

Results

One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight(mean ± SD: −7.7±1.4 kg and −7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units).HOMA-IR, a main endpoint, was significantly reduced following OS (−26.3% [95% CI −49.5, −3.0], p=0.009) and non-significantly following LCD (−20.9% [95% CI −58.2, 16.5). For both groups, there were similar reductions in triglyceridesand LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was anincrease in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsuli-naemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduceduptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery orLCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected.

Conclusions/interpretation

The short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone.Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes followingOS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks.

Trial registration

ClinicalTrials.gov NCT02988011

Funding

This work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union’s Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grants

Background

¹⁵O-water PET is the gold standard for noninvasive quantification of myocardial blood flow. In addition to evaluation of ischemia, the assessment of cardiac function and remodeling is important in all cardiac diseases. However, since ¹⁵O-water is freely diffusible and standard uptake images show little contrast between the myocardium and blood pool, the assessment of left-ventricular (LV) volumes and ejection fraction (EF) is challenging. Therefore, the aim of the present study was to investigate the feasibility of calculating LV volumes and EF from first-pass analysis of ¹⁵O-water PET, by comparison with cardiac magnetic resonance imaging (CMR) using a hybrid PET/MR scanner.

Methods

Twenty-four patients with known or suspected CAD underwent a simultaneous ECG-gated cardiac PET/MR scan. The ¹⁵O-water first-pass images (0-50 seconds) were analyzed using the CarPET software and the CMR images were analyzed using the software Segment, for LV volumes and EF calculations. The LV volumes and EF were compared using correlation and Bland–Altman analysis. In addition, inter- and intra-observer variability of LV volumes and EF were assessed for both modalities.

Results

The correlation between PET and CMR was strong for volumes (r > 0.84) and moderate for EF (r = 0.52), where the moderate correlation for EF was partly due to the small range of EF values. Agreement was high for all parameters, with a slight overestimation of PET values for end-diastolic volume but with no significant mean bias for other parameters. Inter- and intra-observer agreement of volumes was high and comparable between PET and CMR. For EF, inter-observer agreement was higher for PET and intra-observer agreement was higher for CMR.

Conclusion

LV volumes and EF can be calculated by first-pass analysis of a ¹⁵O-water PET scan with high accuracy and comparable precision as with CMR.

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

Background

Respiratory motion during PET imaging reduces image quality. Data-driven gating (DDG) based on principal component analysis (PCA) can be used to identify respiratory signals. The use of DDG, without need for external devices, would greatly increase the feasibility of using respiratory gating in a routine clinical setting. The objective of this study was to evaluate data-driven gating in relation to external hardware gating and regular static image acquisition on PET-MRI data with respect to SUVmax and lesion volumes.

Methods

Sixteen patients with esophageal or gastroesophageal cancer (Siewert I and II) underwent a 6-min PET scan on a Signa PET-MRI system (GE Healthcare) 1.5-2 h after injection of 4 MBq/kg F-18-FDG. External hardware gating was done using a respiratory bellow device, and DDG was performed using MotionFree (GE Healthcare). The DDG raw data files and the external hardware-gating raw files were created on a Matlab-based toolbox from the whole 6-min scan LIST-file. For comparison, two 3-min static raw files were created for each patient. Images were reconstructed using TF-OSEM with resolution recovery with 2 iterations, 28 subsets, and 3-mm post filter. SUVmax and lesion volume were measured in all visible lesions, and noise level was measured in the liver. Paired t-test, linear regression, Pearson correlation, and Bland-Altman analysis were used to investigate difference, correlation, and agreement between the methods.

Results

A total number of 30 lesions were included in the study. No significant differences between DDG and external hardware-gating SUVmax or lesion volumes were found, but the noise level was significantly reduced in the DDG images. Both DDG and external hardware gating demonstrated significantly higher SUVmax (9.4% for DDG, 10.3% for external hardware gating) and smaller lesion volume (- 5.4% for DDG, - 6.6% for external gating) in comparison with non-gated static images.

Conclusions

Data-driven gating with MotionFree for PET-MRI performed similar to external device gating for esophageal lesions with respect to SUVmax and lesion volume. Both gating methods significantly increased the SUVmax and reduced the lesion volume in comparison with non-gated static acquisition. DDG resulted in reduced image noise compared to external device gating and static images.