Increased Insulin Secretion and Glucose Effectiveness in Obese Patients with Type 2 Diabetes following Bariatric Surgery.

Background: ß-cell dysfunction and insulin resistance are the main mechanisms causing glucose intolerance in type 2 diabetes (T2D). Bariatric surgeries, i.e., sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), are procedures both known to induce weight loss, increase insulin action, and enhance ß-cell function, but hepatic insulin extraction and glucose effectiveness may also play a role. Methods: To determine the contribution of these regulators on glucose tolerance after bariatric surgery, an oral glucose tolerance test (OGTT) was performed before and 2 months after surgery in 9 RYGB and 7 SG subjects. Eight healthy subjects served as metabolic controls. Plasma glucose, insulin, C-peptide, GLP-1, and GIP were measured during each OGTT. Insulin sensitivity and secretion, glucose effectiveness, and glucose rate of appearance were determined via oral minimal models. Results: RYGB and SG resulted in similar weight reductions (13%, RYGB (p < 0.01); 14%, SG (p < 0.05)). Two months after surgery, insulin secretion (p < 0.05) and glucose effectiveness both improved equally in the two groups (11%, RYGB (p < 0.01); 8%, SG (p > 0.05)), whereas insulin sensitivity remained virtually unaltered. Bariatric surgery resulted in a comparable increase in the GLP-1 response during the OGTT, whereas GIP concentrations remained unaltered. Following surgery, oral glucose intake resulted in a comparable increase in hepatic insulin extraction, the response in both RYGB and SG patients significantly exceeding the response observed in the control subjects. Conclusions: These results demonstrate that the early improvement in glucose tolerance in obese T2D after RYGB and SG surgeries is attributable mainly to increased insulin secretion and glucose effectiveness, while insulin sensitivity seems to play only a minor role. This trial is registered with NCT02713555.

Normal Splanchnic Blood Flow in a Patient with Severe Stenosis of the Celiac Artery and Superior Mesenteric Artery.

The diagnosis of chronic mesenteric ischaemia is typically based on angiographic findings along with a classic symptomatology. Only a few methods are available for functional testing to establish the diagnosis, such as indirect measurement of the splanchnic blood flow and hepatic vein oxygenation. The present case is a 76-year-old woman with weight loss and intermittent abdominal pain who was clinically suspected of chronic mesenteric ischaemia based on severe stenosis of the celiac artery and superior mesenteric artery. Measurement of the total splanchnic blood flow and hepatic vein oxygenation, however, showed a normal perfusion after meal stimulation, as well as an increased hepatic vein oxygenation, indicating normal flow reserves. This was likely due to a richly developed Riolan's anastomosis arising from the inferior mesenteric artery. The present case advocates the need for functional testing when diagnosing chronic mesenteric ischaemia.

The Laparoscopic Implantation of Neuroprosthesis Procedure Increases Leg Lean Mass in Individuals With Paraplegia Due To Traumatic Spinal Cord Injury.

OBJECTIVES: We hypothesized that the laparoscopic implantation of neuroprosthesis (LION) procedure would significantly alter the body composition of patients with chronic traumatic spinal cord injury (SCI). The objectives were to determine the effect of the LION procedure on lean mass (LM), fatty mass (FM), and bone mineral content (BMC) in patients with SCI. MATERIALS AND METHODS: Five consecutive patients underwent dual-energy x-ray absorptiometry scans before the LION procedure and at the one-year postoperative follow-up to determine changes in LM, FM, and BMC. Student paired t-test was used to determine significance. RESULTS: The patients gained 2506 ± 565 g of LM in the legs (p < 0.001), which was an 18% total increase in leg LM. Total body LM was significantly increased by 3523 ± 1048 g (p < 0.003). FM was unaffected, whereas total BMC showed a small but significant increase of 99 ± 42 g (p = 0.009). CONCLUSIONS: The LION procedure and subsequent neurostimulation procedures resulted in substantial increases in leg LM in patients with chronic traumatic SCI and paraplegia. A possible incremental effect on total BMC also was observed. Further studies are needed to confirm and expand these promising results.

Improvement of the splanchnic blood flow and hepatic vein oxygenation following revascularization in patients with chronic mesenteric ischaemia.

OBJECTIVES: Chronic mesenteric ischaemia (CMI) is an underdiagnosed but severe condition. Access to functional testing is often limited and the diagnosis is usually based primarily on symptoms and imaging. One of the functional tests available is measurement of the splanchnic blood flow (SBF). The purpose of the present investigation was to evaluate if changes in the splanchnic perfusion after revascularization can be detected by measuring the SBF and hepatic vein oxygenation. MATERIALS AND METHODS: The SBF was measured in 10 patients before and after revascularization of the mesenteric arteries by either percutaneous transluminal angioplasty (n = 9) or open revascularization (n = 1). The SBF was measured indirectly using Fick's principle and using the tracer Tc-99m Mebrofenin along with assessment of hepatic blood oxygenation, before and after a standard meal, following catheterization of a hepatic vein and the femoral artery. RESULTS: Nine of 10 patients (90%) achieved a profound increase in SBF after revascularization (mean increase in postprandial response to meal stimulation from 71 ± 95 to 531 ± 295 ml/min, p = 0.001), and an increase in postprandial hepatic vein oxygen saturation (from 52 ± 14% to 59 ± 13%, p = 0.006). The symptoms of the patients diminished accordingly. One patient had no symptom relief, and no increase in postprandial SBF, but an angiographic result with no significant stenosis postrevascularization. CONCLUSIONS: Revascularization increased the SBF and hepatic vein oxygen saturation significantly concurrent with symptom relief and according with the angiographic successful result in the vast majority of patients. A satisfying angiographic result post vascular intervention does not rule out CMI.

Comparable Effects of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass on Basal Fuel Metabolism and Insulin Sensitivity in Individuals with Obesity and Type 2 Diabetes.

Aim: Bariatric surgery improves insulin sensitivity and glucose tolerance in obese individuals with type 2 diabetes (T2D), but there is a lack of data comparing the underlying metabolic mechanisms after the 2 most common surgical procedures Roux-en-Y gastric bypass surgery (RYGB) and sleeve gastrectomy (SG). This study was designed to assess and compare the effects of RYGB and SG on fuel metabolism in the basal state and insulin sensitivity during a two-step euglycemic glucose clamp. Materials and Methods: 16 obese individuals with T2D undergoing either RYGB (n = 9) or SG (n = 7) were investigated before and 2 months after surgery, and 8 healthy individuals without obesity and T2D served as controls. All underwent a 2 h basal study followed by a 5 h 2-step hyperinsulinemic euglycemic glucose clamp at insulin infusion rates of 0.5 and 1.0 mU/kg LBM/min. Results: RYGB and SG induced comparable 15% weight losses, normalized HbA1c, fasting glucose, fasting insulin, and decreased energy expenditure. In parallel, we recorded similar increments (about 100%) in overall insulin sensitivity (M-value) and glucose disposal and similar decrements (about 50%) in endogenous glucose production and FFA levels during the clamp; likewise, basal glucose and insulin concentrations decreased proportionally. Conclusion: Our data suggest that RYGB and SG improve basal fuel metabolism and two-step insulin sensitivity in the liver, muscle, and fat and seem equally favourable when investigated 2 months after surgery. This trial is registered with NCT02713555.

Chronic mesenteric ischaemia: the importance of the individual mesenteric artery.

BACKGROUND: Chronic mesenteric ischaemia (CMI) is a vastly underdiagnosed condition that typically leads to postprandial abdominal pain and weight loss. The aim of the study was to explore the involvement of various mesenteric vessels in total splanchnic blood flow (SBF) and hepatic vein oxygenation. METHODS: Single-blinded comparative trial of 476 patients clinically suspected of CMI. Routine investigation included measurement of hepatic vein oxygen saturation, indirect measurement of the total splanchnic blood flow (SBF), using Fick's principle and the tracer [99m Tc]Mebrofenin, before and after a meal, and digital subtraction angiography. RESULTS: A total of 176 of the 476 patients (36%) had at least one angiographically significant stenosis (lumen reduction ≥70%). In patients with a significant one-vessel disease, the percentage having CMI according to SBF was 10% for a celiac trunk stenosis (n = 60), 50% for a superior mesenteric stenosis (n = 24) and 6% for an inferior mesenteric artery stenosis (n = 34). In patients with a significant two-vessel disease, the percentage with CMI according to SBF response was 92%, 18% and 79%, for no significant stenosis of the celiac trunk (n = 13), superior mesenteric artery (n = 17) and inferior mesenteric artery (n = 19), respectively. CONCLUSION: Patients with significant one- or two-vessel stenosis involving the superior mesenteric artery have a higher likelihood of CMI according to flow criteria and a greater postprandial decrease in hepatic vein saturation on average than patients with no involvement of the superior mesenteric artery.

Intrathoracic Goiter Visualized on iodine-123 and technetium-99m Single-Photon Emission Computed Tomography/Computed Tomography.

Goiter with an intrathoracic component is relatively common; however, it is less common to see extent outside the anterior or posterior mediastinum. We present a case of intrathoracic goiter of significant size and abnormal placement which is examined using both 99mTc-pertechnetate and iodine-123 single-photon emission computed tomography/computed tomography.

European guidelines on chronic mesenteric ischaemia - joint United European Gastroenterology, European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Gastrointestinal and Abdominal Radiology, Netherlands Association of Hepatogastroenterologists, Hellenic Society of Gastroenterology, Cardiovascular and Interventional Radiological Society of Europe, and Dutch Mesenteric Ischemia Study group clinical guidelines on the diagnosis and treatment of patients with chronic mesenteric ischaemia.

Chronic mesenteric ischaemia is a severe and incapacitating disease, causing complaints of post-prandial pain, fear of eating and weight loss. Even though chronic mesenteric ischaemia may progress to acute mesenteric ischaemia, chronic mesenteric ischaemia remains an underappreciated and undertreated disease entity. Probable explanations are the lack of knowledge and awareness among physicians and the lack of a gold standard diagnostic test. The underappreciation of this disease results in diagnostic delays, underdiagnosis and undertreating of patients with chronic mesenteric ischaemia, potentially resulting in fatal acute mesenteric ischaemia. This guideline provides a comprehensive overview and repository of the current evidence and multidisciplinary expert agreement on pertinent issues regarding diagnosis and treatment, and provides guidance in the multidisciplinary field of chronic mesenteric ischaemia.

Improvement in image quality of Tc-99m-based ventilation/perfusion single-photon emission computed tomography in patients with chronic obstructive pulmonary disease through pretest continuous positive airway pressure treatment.

Ventilation/perfusion single-photon emission computed tomography performed using an aerosol of carbon-coated technetium is frequently used for diagnosing pulmonary embolism. Certain patients may suffer from chronic obstructive pulmonary disease (COPD); for such patients, the formation of mucus clots in airways can cause accumulation of the aerosol in the larger airways. This centralized deposition of the aerosol leads to insufficient activity in peripheral lung segments and subsequently results in ventilation images of substandard or even nondiagnostic quality. Continuous positive airway pressure (CPAP) therapy improves airway dynamics and quality of life for COPD patients. We report for the first time the results for two patients for whom initial ventilation scans were of insufficient quality, but diagnostic-quality images were obtained after CPAP therapy.

[Radiology diagnostics and treatment of acute cholecystitis].

Acute cholecystitis (AC) is mainly caused by stones in the gall bladder. Although cholescintigraphy has the highest sensitivity (97%) and specificity (94%) for AC, ultrasound is the most commonly used technique in confirming the diagnosis. Laparoscopic cholecystectomy is the recom-mended treatment of choice; however, in high-risk patients percutaneous gall bladder drainage is an attractive alter-native approach to avoid lesions to the common bile duct. To avoid serious bleeding incidences, it is imperative to pause anticoagulation therapy prior to gall bladder drainage.

Effect of tighter glycemic control on cardiac function, exercise capacity, and muscle strength in heart failure patients with type 2 diabetes: a randomized study.

OBJECTIVES: In patients with type 2 diabetes (T2D) and heart failure (HF), the optimal glycemic target is uncertain, and evidence-based data are lacking. Therefore, we performed a randomized study on the effect of optimized glycemic control on left ventricular function, exercise capacity, muscle strength, and body composition. DESIGN AND METHODS: 40 patients with T2D and HF (left ventricular ejection fraction (LVEF) 35±12% and hemoglobin A1c (HbA1c) 8.4±0.7% (68±0.8 mmol/mol)) were randomized to either 4-month optimization (OPT group) or non-optimization (non-OPT group) of glycemic control. Patients underwent dobutamine stress echocardiography, cardiopulmonary exercise test, 6 min hall-walk test (6-MWT), muscle strength examination, and dual X-ray absorptiometry scanning at baseline and at follow-up. RESULTS: 39 patients completed the study. HbA1c decreased in the OPT versus the non-OPT group (8.4±0.8% (68±9 mmol/mol) to 7.6±0.7% (60±7 mmol/mol) vs 8.3±0.7% (67±10 mmol/mol) to 8.4±1.0% (68±11 mmol/mol); p<0.001). There was no difference between the groups with respect to changes in myocardial contractile reserve (LVEF (p=0.18)), oxygen consumption (p=0.55), exercise capacity (p=0.12), and 6-MWT (p=0.84). Muscle strength decreased in the non-OPT compared with the OPT group (37.2±8.1 to 34.8±8.3 kg vs 34.9±10.2 to 35.4±10.7 kg; p=0.01), in line with a non-significant decrease in lean (p=0.07) and fat (p=0.07) tissue mass in the non-OPT group. Hypoglycemia and fluid retention did not differ between groups. CONCLUSIONS: 4 months of optimization of glycemic control was associated with preserved muscle strength and lean body mass in patients with T2D and HF compared with lenient control, and had no deleterious effect on left ventricular contractile function and seemed to be safe. TRIAL REGISTRATION NUMBER: NCT01213784; pre-results.

The influence of the gastrointestinal tract and the liver on cystatin C serum concentrations.

OBJECTIVE: The purpose of this study in humans was to examine the influence of the gastrointestinal tract and liver on the serum concentrations of cystatin C. METHODS: Eighteen healthy volunteers and 28 patients suspected of having chronic intestinal ischemia underwent catheterization of the abdominal aorta and the central hepatic vein. Blood samples were taken simultaneously from the abdominal aorta and the central hepatic vein 60, 90 and 120 minutes after the start of the investigation. After the first blood sample, a standard liquid meal was ingested. Measurement of splanchnic blood flow was performed using the Fick principle with constant infusion of (99m)Tc-Bridatec. Angiography was performed at the end of the investigation. RESULTS: The splanchnic blood flow increased significantly postprandially in the healthy volunteers and in the patients with normal angiography by 0.613-0.698 L/min and increased non- significantly in the patients with abnormal angiography (n = 5) by 0.135 L/min on average. ANOVA and the Bonferroni's multiple comparison test showed no significant difference between the means of cystatin C, creatinine or urea in the samples taken 60, 90 and 120 minutes after the start of the investigation in the abdominal aorta and the hepatic vein in the healthy volunteers or in the patients suspected of chronic intestinal ischemia with normal angiography. CONCLUSION: There was no indication of hepatic elimination of cystatin C, creatinine or urea. The serum concentrations of cystatin C, creatinine and urea in the central hepatic vein and the abdominal aorta were independent of the splanchnic blood flow.

Chronic intestinal ischemia and splanchnic blood-flow: reference values and correlation with body-composition.

AIM: To determine the splanchnic blood flow and oxygen uptake in healthy-subjects and patients and to relate the findings to body-composition. METHODS: The total splanchnic blood flow (SBF) and oxygen uptake (SO2U) were measured in 20 healthy volunteers (10 women) and 29 patients with suspected chronic intestinal ischemia (15 women), age 40-85 years, prior to and after a standard meal. The method is based on the Fick principle using the continuous infusion of an indicator (99mTechnetium-labelled mebrofenin) and catheterization of an artery and the hepatic vein. An angiography of the intestinal arteries was performed during the same investigation. A whole-body dual-energy x-ray absorptiometry scan was performed in healthy volunteers to determine body composition. RESULTS: Angiography revealed no atherosclerotic lesions in the intestinal arteries. The mean baseline SBF was 1087 mL/min (731-1390), and this value increased significantly to 1787 mL/min after the meal in healthy volunteers (P < 0.001). The baseline SBF in patients was 1080 mL/min, which increased to 1718 mL/min postprandially (P < 0.001). The baseline SBF was independent of age, sex, lean body mass and percentage of body fat. The mean meal-induced increase in SBF was equal to 282 mL/min + 5.4 mL/min × bodyweight, (P = 0.025). The SO2U in healthy volunteers and patients was 50.7 mL/min and 48.0 mL/min, respectively, and these values increased to 77.5 mL/min and 75 mL/min postprandially, respectively. Both baseline and postprandial SO2U were directly related to lean body mass. Age and sex exerted no impact on SO2U. CONCLUSION: A direct correlation between body weight and the postprandial increase in SBF was observed. The effect of body weight should be considered in the diagnosis of chronic intestinal ischemia.

Validation of 99mTechnetium-labeled mebrofenin hepatic extraction method to quantify meal-induced splanchnic blood flow responses using a porcine model.

The aim of this study was to evaluate the measurement of the total splanchnic blood flow (SBF) using a clinical diagnostic method based on Fick's principle and hepatic extraction of 99mTc-mebrofenin (99mTc-MBF) compared with a paraaminohippuric acid (pAH) dilution method in a porcine model. Another aim was to investigate whether enterohepatic cycling of 99mTc-MBF affected the SBF measurement. Five indwelling catheters were placed in each pig (n = 15) in the portal, mesenteric, and hepatic veins, as well as in the aorta and the vena cava. The SBF was measured using both methods. The portal blood flow; the intestinal and hepatic oxygen uptake; the net fluxes of oxygen, lactate, and glucose; and the extraction fraction (EF) of 99mTc-MBF were measured before and for 70 min after feeding. The mean baseline SBF was 2,961 ml/min vs. 2,762 ml/min measured by pAH and 99mTc-MBF, respectively, and increased significantly to 3,977 ml/min and 3,981 ml/min postprandially. The hepatic EF of 99mTc-MBF decreased from 40% at the start of the investigation to 16% 70 min after feeding. The arterial-portal difference in 99mTc-MBF concentration was 0.21% (P = 0.48), indicating no intestinal extraction or metabolism. The clinical method for measuring the SBF based on hepatic 99mTc-MBF extraction is robust compared with the indicator dilution method, despite the decrease seen in hepatic extraction of 99mTc-MBF. Because there was no difference in the content of 99mTc-MBF between the arterial and portal vein plasma, the SBF can be calculated from an arterial and a hepatic vein sample.

Samarium-153 treatment of bone pain in patients with metastatic prostate cancer.

INTRODUCTION: Painful bone metastases are common in advanced prostate cancer. We report the clinical outcome after administration of Samarium-153 ((153)Sm), an emitter of beta-particles that concentrates in the areas of enhanced osteoblastic activity. METHODS: Twenty-two patients (median age 73 years) with metastatic, hormone-refractory prostate cancer received a single bolus infusion of (153)Sm (37 MBq/kg). All patients had painful bone metastases to more than one anatomical region, and most had inadequate pain relief to narcotic analgesics. Bone specific pain, analgesic score according to WHO, ECOG performance status, and blood count were evaluated before and up to 28 weeks after treatment. RESULTS: Median follow-up was six weeks (mean 14 weeks). Eleven patients died within the 28 week observation period (ten from terminal disease), and four patients had their observation period truncated. Median pain score was 56.3%, 50.0%, and 50.0% of baseline values at week 4 (n = 20), 16 (n = 10), and 28 (n = 7), respectively. A reduction of baseline pain score by 50% or more was observed in 50%, 70% and 71% of patients at week 4, 16, and 28, respectively. Hematological toxicity was mild and reversible in most cases. CONCLUSION: Administration of (153)Sm to prostate cancer patients with painful bone metastases offered clinical relevant pain relief with tolerable hematological toxicity.

Functional versus radiological assessment of chronic intestinal ischaemia.

INTRODUCTION: The diagnosis chronic intestinal ischaemia (CII) is based on the clinical symptoms postprandial pain and weight loss combined with abnormal findings during angiography. Despite the well-known poor correlation between symptoms and morphology, physiological tests are rarely performed. PERSPECTIVES: It is possible to measure the total splanchnic blood flow (SBF) before and after a test meal, and the results supply additional information to the morphologic investigations. To date, no papers have addressed the impact of morphologic changes of the mesenteric arteries on the SBF. MATERIALS AND METHODS: Forty-six consecutive patients suspected of CII were investigated. The routine investigation included angiography and measurements of the SBF before and after a test meal. Measurements of the total SBF were performed using the 'Fick principle'. (99m)Technetium-labelled Mebrofenin was used as a tracer. Digital subtraction angiography was performed. RESULTS: Agreement between SBF and angiography was found in 44 of 46 patients. Mean baseline SBF for all patients was 985 ml/min, total range (525-1932) and within the reported normal range. The mean postprandial increase in SBF was 480 mL min(-1) (-130 to 1353), thus 36 patients were categorized as normal by both angiography and SBF, eight patients were abnormal by both methods and two patients had abnormal SBF but normal angiography. DISCUSSION: In this cohort, SBF detects CII with sensitivity of 1.0, and specificity of 0.95. SBF supplies additional information in patients with convincing symptoms and normal angiography. In these patients, the affection of the intestinal arteries may be too distant or too subtle to be visualized on angiography.

[Patient with hypertension and bilateral renal artery stenosis]. / Bilateral nyrearteriestenose hos en patient med hypertension.

A patient story regarding a young man with hypertension and bilateral renal artery stenosis is presented. The value of renography/captopril renography in connection with selective renal vein renin sampling is discussed.

Chronic intestinal ischaemia: diagnosis.

Chronic intestinal ischaemia is a relatively rare but very important clinical entity, which is caused by a reduction in the splanchnic blood flow, most often because of atherosclerosis. Intestinal angina is postprandial abdominal pain developing when the genuine and collateral vessels no longer are able to accommodate the postprandial increasing demand from the gastrointestinal tract and the liver. In addition, the clinical picture very often includes sitophobia and weight loss. In daily clinical practice, conventional angiography is considered as the gold standard, but ultra sonography, computerized tomography and magnetic resonance angiography are gaining momentum when investigating for chronic intestinal ischaemia. These methods depend on imaging of the stenotic vessels not taking into consideration the possibility of sufficient splanchnic perfusion in spite of severely stenotic or occluded vessels. Only a few papers address the physiological consequence of stenotic or occluded vessels - the lack of postprandial increase in splanchnic blood flow.