Splanchnic Metabolism and Blood Flow In Man. PET Studies with Reference to Obesity and Diabetes

Splanchnic region comprises the interaction of multiple organs, hormones and neural factors and is a critical regulator of glucose homeostasis during both postabsorptive and absorptive states. While splanchnic functions deteriorate during long-standing obesity predisposing to impaired glucose regulation and type 2 diabetes, many of the aspects of splanchnic metabolism and blood flow (BF) in health and disease are still unknown. In the present work, validation of positron emission tomography (PET) for the measurement of pancreatic and intestinal metabolism and BF in vivo was carried out and thereafter the method was applied to a total of 62 morbidly obese and 40 healthy individuals. In a set of cross-sectional and longitudinal studies glycemic control and β-cell function, splanchnic glucose and lipid metabolism, and splanchnic vascular responses to a mixed-meal, incretin infusions and glucose loading were explored before and after bariatric surgery and weight loss. Compared to healthy controls, pancreatic fatty acid (FA) uptake and steatosis were markedly increased in obese patients whereas pancreatic glucose uptake (GU) and BF were impaired. Elevated pancreatic steatosis and inadequate BF were associated with poor insulin secretion rate. In the small intestine, insulin upregulated GU nearly three-fold over the fasting values in healthy controls whereas normally glucose tolerant obese patients were unresponsive to the stimulatory effect of insulin. In lean controls and patients with type 2 diabetes, mixed-meal increased both pancreatic and intestinal BF, whereas GIP infusion decreased and increased pancreatic and intestinal BF, respectively. Bariatric surgery was followed by a prominent weight loss, increase in insulin sensitivity and β-cell function, and decrease in pancreatic FA uptake, rate of steatosis and BF. While the vascular responses of GIP were essentially similar at post-surgery when compared to pre-surgery, splanchnic vascular responses during mixed-meal were enchanced, likely as a result of rapid gastric emptying. In conclusion, pancreatic and small intestinal metabolism and BF respond to obesity and type 2 diabetes, and to metabolic changes elicited by bariatric surgery. The adequacy of pancreatic BF responses and insulin-dependence of intestinal GU are pivotal concepts in the regulation of glucose homeostasis in humans. Obesity influences both of these physiological concepts, whereas altered gastrointestinal anatomy, incretins responses and weight loss after bariatric surgery are able to reverse these obesity-induced perturbations leading to improved glucose homeostasis.Maha-suolikanavan aineenvaihdunta ihmisellä. PET-tutkimuksia lihavilla ja diabetesta sairastavilla potilailla Maha-suolikanavan alue käsittää lukuisten elinten, hormonien ja hermostollisten tekijöiden välisen vuorovaikutuksen ja se on keskeinen veren glukoositasapainoa säätelevä kokonaisuus niin paastossa kuin aterianjälkeisessä tilanteessa. Vaikka lihavuuden on osoitettu muuttavan maha-suolikanavan toimintaa altistaen heikentyneelle glukoosinsiedolle ja tyypin 2 diabetekselle, monia tämän alueen aineenvaihdunnallisia ja verenvirtaukseen liittyviä tekijöitä ei tunneta terveessä elimistössä eikä sairaustiloissa. Väitöskirjatyössäni osoitin että positroniemissiotomografia eli PET-kuvaus soveltuu haiman ja suoliston glukoosi- ja rasvahappoaineenvaihdunnan ja verenvirtauksen mittaamiseen ihmisillä kajoamattomasti. Tämän jälkeen hyödynsin PET-menetelmää erilaisissa tutkimusasetelmissa 62 lihavalla ja 40 terveellä koehenkilöllä. Lisäksi tutkimuksissa tarkasteltiin lihavuusleikkauksen vaikutusta koko kehon glukoosiaineenvaihduntaan ja haiman beetasolujen toimintaan. Tutkimuksessa todettiin että lihavilla koehenkilöillä oli suurentunut haiman rasvahappoaineenvaihdunta ja heidän haimansa olivat rasvoittuneempia kuin terveillä verrokeilla. Lihavien koehenkilöiden haiman glukoosiaineenvaihdunta ja verenvirtaus oli heikentynyt. Terveillä verrokeilla insuliini lisäsi suoliston glukoosinottokykyä lähes kolminkertaisesti paastonaikaiseen tilanteeseen verrattuna. Sen sijaan lihavilla koehenkilöillä insuliinin anto ei vaikuttanut suoliston glukoosinottokykyyn. Terveillä verrokeilla ruokailu lisäsi sekä haiman että suoliston verenvirtausta, kun taas GIP-hormonin annon aikana haiman verenvirtaus laski ja suoliston nousi. Lihavuusleikkauksen myötä haiman rasva-aineenvaihdunta ja verenvirtaus laskivat merkitsevästi. GIP-hormonin vaikutukset maha-suolikanavan verenvirtaukseen olivat samanlaisia sekä ennen leikkausta että sen jälkeen. Sen sijaan leikkauksenjälkeisessä tilanteessa ruokailun aiheuttamat maha-suolikanavan verenvirtausvasteet kiihtyivät johtuen todennäköisesti suurentuneesta mahalaukun tyhjenemisnopeudesta. Tutkimuksen perusteella maha-suolikanavan alueen elimissä tapahtuu lukuisia muutoksia lihavuuden, tyypin 2 diabeteksen ja lihavuusleikkauksen myötä. Haiman verenvirtausvasteet ja suoliston insuliinista riippuvainen glukoosinottokyky ovat merkittäviä koko kehon aineenvaihduntaa sääteleviä ilmiöitä. Vaikka lihavuus näyttää muuttavan näitä ilmiöitä, lihavuusleikkaus ja sen vaikutukset maha-suolikanavan anatomiaan, suolisto-hormonien eritykseen ja painoon kykenevät palauttamaan haitalliset muutokset johtaen parempaan glukoositasapainoon.Siirretty Doriast

SGLT2:n estäjät : diabeteslääkkeet suojelevat sydäntä

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Obesity associated blunted subcutaneous adipose tissue blood flow after meal is improved after bariatric surgery

Background and aims: GIP and meal ingestion increase subcutaneous adipose tissue (SAT) perfusion in healthy subjects. Effects of GIP and meal on visceral adipose tissue (VAT) perfusion is unclear. Our aim was to investigate the effects of meal and GIP on VAT and SAT perfusion in obese subjects with type 2 diabetes (T2DM) before and after bariatric surgery.Materials and methods: We recruited 10 obese subjects with T2DM scheduled for bariatric surgery and 10 control subjects. Subjects were studied under two stimulations: meal ingestion and GIP infusion. SAT and VAT perfusion was measured using 15O-H2O PET-MRI at three time points: baseline, 20min and 50min after start of stimulation. Obese subjects were studied before and after bariatric surgery.Results: Before bariatric surgery the responses of SAT perfusion to meal (p=0.04) and GIP-infusion (p=0.002) were blunted in the obese subjects compared to the controls. VAT perfusion response did not differ between obese and control subjects after meal or GIP-infusion.After bariatric surgery SAT perfusion response to meal was similar to that of control subjects. SAT perfusion response to GIP administration remained lower in operated than control subjects. There was no change in VAT perfusion response after bariatric surgery.Conclusions: The vasodilating effects of GIP and meal are blunted in SAT but not in VAT in obese subjects with T2DM. Bariatric surgery improves the effects of meal on SAT perfusion, but not the effects of GIP. Postprandial increase in SAT perfusion after bariatric surgery seems to be regulated in a GIP independent manner.</p

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

Rethinking health:ICT-enabled services to empower people to manage their health

Lifestyle is a key determinant in the prevention and management of chronic diseases. If we would exercise regularly, eat healthy, control our weight, sleep enough, manage stress, not smoke and use alcohol only moderately, 90% of type II diabetes, 80% of coronary heart disease, and 70% of stroke could be prevented. Health statistics show that lifestyle related diseases are increasing at an alarming rate. Public health promotion campaigns and healthcare together are not effective enough to stop this "tsunami". The solution that is offered is to empower people to manage their health with the assistance of ICT-enabled services. A lot of R&amp;D and engineering effort is being invested in Personal Health Systems. Although some progress has been made, the market for such systems has not yet emerged. The aim of this critical review is to identify the barriers which are holding back the growth of the market. It looks into the theoretical foundations of behavior change support, the maturity of the technologies for behavior change support, and the business context in which behavior change support systems are used

Bariatric surgery enhances splanchnic vascular responses in patients with type 2 diabetes

Bariatric surgery results in notable weight loss and alleviates hyperglycemia in patients with type 2 diabetes (T2D). We aimed to characterize the vascular effects of a mixedmeal and infusion of exogenous glucose-dependent insulinotropic polypeptide (GIP) in the splanchnic region in 10 obese patients with T2D before and after bariatric surgery and in 10 lean control subjects. The experiments were carried out on two separate days. Pancreatic and intestinal blood flow (BF) were measured at baseline, 20 min, and 50 min with 15O-water by using positron emission tomography and MRI. Before surgery, pancreatic and intestinal BF responses to a mixed meal did not differ between obese and lean control subjects. Compared with presurgery, the mixed meal induced a greater increase in plasma glucose, insulin, and GIP concentrations after surgery, which was accompanied by a marked augmentation of pancreatic and intestinal BF responses. GIP infusion decreased pancreatic but increased small intestinal BF similarly in all groups both before and after surgery. Taken together, these results demonstrate that bariatric surgery leads to enhanced splanchnic vascular responses as a likely consequence of rapid glucose appearance and GIP hypersecretion

<strong>Bariatric surgery alters the postprandial recovery from hypoglycemia mediated by cholinergic signal </strong>

   Roux-en-Y gastric bypass surgery (GB) and sleeve gastrectomy (SG) increase prandial insulin and glucagon secretion but reduce the endogenous glucose production (EGP) response to hypoglycemia compared to non-operated controls (CN), suggesting that parasympathetic nervous system (PNS) plays a role. Here, we investigated the effect of acute PNS blockade on the post-meal counterregulatory response to insulin-induced hypoglycemia in GB and SG compared to CN. Glucose kinetics and islet-cell secretion were measured in 9 non-diabetic subjects with GB, 7 with SG, and 5 CN during hyperinsulinemic hypoglycemic clamp (~3.2mM) combined with meal ingestion on two separate days with and without intravenous atropine infusion. Glucose and hormonal levels were similar at baseline and during steady state hypoglycemia before meal ingestion in 3 groups and unaffected by atropine. Atropine infusion diminished prandial systemic appearance of ingested glucose (RaO) by 30%, EGP by 40%, and glucagon response to hypoglycemia by 90%, in controls. In GB or SG, blocking PNS had no effect on the RaO or meal-induced hyperglucagonemia, but increased EGP in SG without any effect in GB (p<0.05 interaction). These findings indicate that cholinergic signal contributes to the recovery from hypoglycemia by meal consumption in humans. However, bariatric surgery dissipates PNS-mediated physiologic responses to hypoglycemia in the fed state. </p

Liver blood dynamics after bariatric surgery : The effects of mixed-meal test and incretin infusions

Aims/hypothesis: The mechanisms for improved glycemic control after bariatric surgery in subjects with type 2 diabetes (T2D) are not fully known. We hypothesized that dynamic hepatic blood responses to a mixed-meal are changed after bariatric surgery in parallel with an improvement in glucose tolerance. Methods: A total of ten morbidly obese subjects with T2D were recruited to receive a mixed-meal and a glucose-dependent insulinotropic polypeptide (GIP) infusion before and early after (within a median of less than three months) bariatric surgery, and hepatic blood flow and volume (HBV) were measured repeatedly with combined positron emission tomography/MRI. Ten lean non-diabetic individuals served as controls. Results: Bariatric surgery leads to a significant decrease in weight, accompanied with an improved β-cell function and glucagon-like peptide 1 (GLP-1) secretion, and a reduction in liver volume. Blood flow in portal vein (PV) was increased by 1.65-fold (P = 0.026) in response to a mixed-meal in subjects after surgery, while HBV decreased in all groups (P < 0.001). When the effect of GIP infusion was tested separately, no change in hepatic arterial and PV flow was observed, but HBV decreased as seen during the mixed-meal test. Conclusions/interpretation: Early after bariatric surgery, PV flow response to a mixed-meal is augmented, improving digestion and nutrient absorption. GIP influences the post-prandial reduction in HBV thereby diverting blood to the extrahepatic sites

Obesity-associated Blunted Subcutaneous Adipose Tissue Blood Flow After Meal Improves After Bariatric Surgery

Context: Glucose-dependent insulinotropic peptide (GIP) and meal ingestion increase subcutaneous adipose tissue (SAT) perfusion in healthy individuals. The effects of GIP and a meal on visceral adipose tissue (VAT) perfusion are unclear. Objective: Our aim was to investigate the effects of meal and GIP on VAT and SAT perfusion in obese individuals with type 2 diabetes mellitus (T2DM) before and after bariatric surgery. Methods: We recruited 10 obese individuals with T2DM scheduled for bariatric surgery and 10 control individuals. Participants were studied under 2 stimulations: meal ingestion and GIP infusion. SAT and VAT perfusion was measured using 15O-H2O positron emission tomography-magnetic resonance imaging at 3 time points: baseline, 20 minutes, and 50 minutes after the start of stimulation. Obese individuals were studied before and after bariatric surgery. Results: Before bariatric surgery the responses of SAT perfusion to meal (P = .04) and GIP-infusion (P = .002) were blunted in the obese participants compared to controls. VAT perfusion response did not differ between obese and control individuals after a meal or GIP infusion. After bariatric surgery SAT perfusion response to a meal was similar to that of controls. SAT perfusion response to GIP administration remained lower in the operated-on than control participants. There was no change in VAT perfusion response after bariatric surgery. Conclusion: The vasodilating effects of GIP and meal are blunted in SAT but not in VAT in obese individuals with T2DM. Bariatric surgery improves the effects of a meal on SAT perfusion, but not the effects of GIP. Postprandial increase in SAT perfusion after bariatric surgery seems to be regulated in a GIP-independent manner

Effects of meal and incretins in the regulation of splanchnic blood flow

Objective: Meal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions. Design: A non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation was performed. Methods: Effects of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) infusions and mixed-meal were tested in 10 healthy, glucose tolerant subjects using PET-MRI multimodal imaging technology. Intestinal and pancreatic BF and blood volume (BV) were measured with 15O-water and 15O-carbon monoxide, respectively. Results: Ingestion of a mixed-meal led to an increase in pancreatic and jejunal BF, whereas duodenal BF was unchanged. Infusion of GIP and GLP-1 reduced BF in the pancreas. However, GIP infusion doubled blood flow in the jejunum with no effect of GLP-1. Conclusion: Together, our data suggest that meal ingestion leads to increases in pancreatic BF accompanied by a GIP-mediated increase in jejunal but not duodenal blood flow