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Incretin-based therapy is an antidiabetic and antiobesity approach mimicking glucagon-like peptide-1 (GLP-1) with additional end-organ protection. This review solely focuses on randomized, controlled mechanistic human studies, investigating the renal effects of GLP-1. There is no consensus about the localization of GLP-1 receptors (GLP-1Rs) in human kidneys. Rodent and primate data suggest GLP-1R distribution in smooth muscle cells in the preglomerular vasculature. Native GLP-1 and GLP-1R agonists elicit renal effects. Independently of renal plasma flow and glomerular filtration rate, GLP-1 has a natriuretic effect but only during volume expansion. This is associated with high renal extraction of GLP-1, suppression of angiotensin II, and increased medullary as well as cortical perfusion. These observations may potentially indicate that impaired GLP-1 sensing could establish a connection between salt sensitivity and insulin resistance. It is concluded that a functional GLP-1 kidney axis exists in humans, which may play a role in renoprotection., Incretin-based therapy is an antidiabetic and antiobesity approach mimicking glucagon-like peptide-1 (GLP-1) with additional end-organ protection. This review solely focuses on randomized, controlled mechanistic human studies, investigating the renal effects of GLP-1. There is no consensus about the localization of GLP-1 receptors (GLP-1Rs) in human kidneys. Rodent and primate data suggest GLP-1R distribution in smooth muscle cells in the preglomerular vasculature. Native GLP-1 and GLP-1R agonists elicit renal effects. Independently of renal plasma flow and glomerular filtration rate, GLP-1 has a natriuretic effect but only during volume expansion. This is associated with high renal extraction of GLP-1, suppression of angiotensin II, and increased medullary as well as cortical perfusion. These observations may potentially indicate that impaired GLP-1 sensing could establish a connection between salt sensitivity and insulin resistance. It is concluded that a functional GLP-1 kidney axis exists in humans, which may play a role in renoprotection.

Objective: Visceral fat mass (VFM) is a risk factor for cardiovascular diseases, type 2 diabetes mellitus, and malignancy; however, normative data are limited. The aim of this study was to provide reference data for VFM from a large, apparently healthy Caucasian adult population. Methods: Volunteers aged 20 to 93 years from the Copenhagen City Heart Study had a standardized whole-body dual-energy x-ray absorptiometry scan performed using the iDXA (GE Lunar). Total and regional fat mass was measured. VFM was quantified using the CoreScan application. Results: A total of 1277 participants were included (708 women, mean [SD], age: 56 [19] years, height: 1.66 [0.07] m, BMI: 24.64 [4.31] kg/m2; and 569 men, age: 57 [18] years, height: 1.80 [0.07] m, BMI: 25.99 [3.86] kg/m2). Increased VFM was positively correlated with age in both sexes. Men had significantly higher VFM in mass (g) after normalization to body size (m2) and total fat mass (p < 0.001). VFM increased more in women with high values of the android/gynoid ratio. Conclusions: Normative data of VFM from a large, healthy Danish cohort aged 20 to 93 years are presented. VFM increased with age in both sexes, but men had significantly higher VFM compared with women with the same BMI, body fat percentage, and fat mass index.

Background The dopamine transporter (DaT) PET ligand [18F]FE-PE2I is used to aid the diagnosis of Parkinson’s disease. After encountering four patients with a history of daily sertraline use, who all showed atypical findings on [18F]FE-PE2I PET, we suspected that the selective serotonin reuptake inhibitor (SSRI), sertraline, might interfere with the results and lead to globally reduced striatal [18F]FE-PE2I binding due to sertraline’s high affinity for DaT. Methods We rescanned the four patients with [18F]FE-PE2I PET after a 5-day sertraline pause. Sertraline plasma concentration was estimated based on body weight and dose, and specific binding ratios (SBR) in caudate nucleus, known to be more preserved in Parkinson’s, were used to estimate the effect on tracer binding. Comparison was made to a patient with [18F]FE-PE2I PET before and after a 7-day Modafinil pause. Results We found a significant effect of sertraline on caudate nucleus SBR (p = 0.029). The effect showed a linear dose-dependent relationship that corresponds to a reduction in SBR by 0.32 or 0.44 for a 75 kg male or a 65 kg female, respectively, taking a daily dose of 50 mg sertraline. Conclusion Sertraline is one of the most commonly used antidepressants and in contrast to other SSRI’s, sertraline show high affinity for DaT. We recommend that sertraline treatment is taken into account when patients are undergoing [18F]FE-PE2I PET especially in patients showing apparent globally reduced PE2I binding. If tolerable, pausing of the sertraline treatment should be considered, especially for doses above 50 mg/day., Background: The dopamine transporter (DaT) PET ligand [18F]FE-PE2I is used to aid the diagnosis of Parkinson’s disease. After encountering four patients with a history of daily sertraline use, who all showed atypical findings on [18F]FE-PE2I PET, we suspected that the selective serotonin reuptake inhibitor (SSRI), sertraline, might interfere with the results and lead to globally reduced striatal [18F]FE-PE2I binding due to sertraline’s high affinity for DaT. Methods: We rescanned the four patients with [18F]FE-PE2I PET after a 5-day sertraline pause. Sertraline plasma concentration was estimated based on body weight and dose, and specific binding ratios (SBR) in caudate nucleus, known to be more preserved in Parkinson’s, were used to estimate the effect on tracer binding. Comparison was made to a patient with [18F]FE-PE2I PET before and after a 7-day Modafinil pause. Results: We found a significant effect of sertraline on caudate nucleus SBR (p = 0.029). The effect showed a linear dose-dependent relationship that corresponds to a reduction in SBR by 0.32 or 0.44 for a 75 kg male or a 65 kg female, respectively, taking a daily dose of 50 mg sertraline. Conclusion: Sertraline is one of the most commonly used antidepressants and in contrast to other SSRI’s, sertraline show high affinity for DaT. We recommend that sertraline treatment is taken into account when patients are undergoing [18F]FE-PE2I PET especially in patients showing apparent globally reduced PE2I binding. If tolerable, pausing of the sertraline treatment should be considered, especially for doses above 50 mg/day.

Background 82Rb PET and [15O]H2O PET are both validated tracers for myocardical perfusion imaging but have not previously been compared clinically. During our site’s transition from 82Rb to [15O]H2O PET, we performed a head-to-head comparison in a mixed population with suspected ischemic heart disease. Methods A total of 37 patients referred for perfusion imaging due to suspicion of coronary stenosis were examined with both 82Rb and [15O]H2O PET on the same day in rest and during adenosine-induced stress. The exams were rated by two blinded readers as normal, regional ischemia, globally reduced myocardial perfusion, or myocardial scarring. For [15O]H2O PET, regional ischemia was defined as two neighboring segments with average stress perfusion ≤ 2.3 mL/(min·g). Further, we evaluated a total perfusion deficit (TPD) of ≥ 10% as a more conservative marker of ischemia. Results [15O]H2O PET identified more patients with regional ischemia: 17(46%) vs 9(24%), agreement: 59% corresponding to a Cohen’s kappa of .31 [95%CI .08-.53], (P < .001). Using the more conservative TPD ≥ 10%, the agreement increased to 86% corresponding to a kappa of .62 [95%CI .33-.92], (P = .001). For the subgroup of patients with no known heart disease (n = 18), the agreement was 94%. Interrater agreement was 95% corresponding to a kappa of .89 [95%CI .74-1.00] (P < .001). Conclusions In clinical transition from 82Rb to [15O]H2O PET, it is important to take into account the higher frequency of patients with regional ischemia detected by [15O]H2O PET., Background: 82Rb PET and [15O]H2O PET are both validated tracers for myocardical perfusion imaging but have not previously been compared clinically. During our site’s transition from 82Rb to [15O]H2O PET, we performed a head-to-head comparison in a mixed population with suspected ischemic heart disease. Methods: A total of 37 patients referred for perfusion imaging due to suspicion of coronary stenosis were examined with both 82Rb and [15O]H2O PET on the same day in rest and during adenosine-induced stress. The exams were rated by two blinded readers as normal, regional ischemia, globally reduced myocardial perfusion, or myocardial scarring. For [15O]H2O PET, regional ischemia was defined as two neighboring segments with average stress perfusion ≤ 2.3 mL/(min·g). Further, we evaluated a total perfusion deficit (TPD) of ≥ 10% as a more conservative marker of ischemia. Results: [15O]H2O PET identified more patients with regional ischemia: 17(46%) vs 9(24%), agreement: 59% corresponding to a Cohen’s kappa of.31 [95%CI.08-.53], (P < .001). Using the more conservative TPD ≥ 10%, the agreement increased to 86% corresponding to a kappa of.62 [95%CI.33-.92], (P = .001). For the subgroup of patients with no known heart disease (n = 18), the agreement was 94%. Interrater agreement was 95% corresponding to a kappa of.89 [95%CI.74-1.00] (P < .001). Conclusions: In clinical transition from 82Rb to [15O]H2O PET, it is important to take into account the higher frequency of patients with regional ischemia detected by [15O]H2O PET. Graphical Abstract: [Figure not available: see fulltext.].

PURPOSE: The natriuretic effect of GLP-1 in humans is independent of changes in renal plasma flow (RPF) and glomerular filtration rate (GFR) but may involve suppression of angiotensin II (ANG II) and a significant (~45%) renal extraction of GLP-1. The current study was designed to investigate the consequences for the renal extraction and the natriuretic effect of blocking GLP-1 receptors with the specific GLP-1 receptor antagonist, exendin 9-39 (Ex 9-39).METHODS: Under fixed sodium intake for 4 days before each study day, 6 healthy male participants were recruited from our recent study where GLP-1 or vehicle was infused (1). In the present new experiments, participants were examined during a 3-hour infusion of GLP-1 (1.5 pmol/kg/min) together with a 3.5-hour infusion of Ex 9-39 (900 pmol/kg/min). Timed urine collections were conducted throughout the experiments. Renal extraction of GLP-1 as well as RPF and GFR were measured via Fick's principle after catheterization of a renal vein. Arterial plasma renin, ANG II, and aldosterone concentrations were measured.RESULTS: Co-infusion of Ex 9-39 significantly reduced renal extraction of GLP-1 to ~25% compared with GLP-1 infusion alone (~45%). Urinary sodium excretions remained at baseline levels during co-infusion of Ex 9-39 as well as vehicle. By contrast, GLP-1 infusion alone resulted in a 2-fold increase in natriuresis. Ex 9-39 abolished the GLP-1-induced decrease in arterial ANG II concentrations. RPF and GFR remained unchanged during all experiments.CONCLUSIONS: Renal extraction of GLP-1 and its effect on natriuresis are both dependent on GLP-1 receptor activation in healthy humans.

Human studies have demonstrated that physiologically relevant changes in circulating glucagon-like peptide-1 (GLP-1) elicit a rapid increase in renal sodium excretion when combined with expansion of the extracellular fluid volume. Other studies support the involvement of various gastrointestinal hormones, e.g., gastrin and cholecystokinin (CCK) in a gut-kidney axis, responsible for a rapid-acting feed-forward natriuretic mechanism. This study was designed to investigate the hypothesis that the postprandial GLP-1 plasma concentration is sensitive to the sodium content in the meal. Under fixed sodium intake for 4 days prior to each experimental day, 10 lean healthy male participants were examined twice in random order after a 12-hr fasting period. Arterial blood samples were collected at 10-20-min intervals for 140 min after 75 grams of oral glucose + 6 grams of oral sodium chloride (NaCl) load versus 75 grams of glucose alone. Twenty-four-hour baseline urinary sodium excretions were similar between study days. Arterial GLP-1 levels increased during both oral glucose loads and were significantly higher at the 40-80 min period during glucose + NaCl compared to glucose alone. The postprandial arterial responses of CCK, gastrin, and glucose-dependent insulinotropic polypeptide as well as glucose, insulin, and C-peptide did not differ between the two study days. Arterial renin, aldosterone, and natriuretic peptides levels did not change within subjects or between study days. Angiotensin II levels were significantly lower at the time GLP-1 was higher (60-80 min) during glucose + NaCl. Sodium intake in addition to a glucose load selectively amplifies the postprandial GLP-1 plasma concentration. Thus, GLP-1 may be part of an acute feed-forward mechanism for natriuresis.

BACKGROUND: Despite no international consensus on the diagnostic criteria for sarcopenia, low lean mass, muscle strength, and physical function are important risk factors for disability, frailty, and mortality in older individuals, as well as in a wide range of patients with muscle loss. Here, we provide a population-based reference material of total and regional lean body mass, muscle strength/power parameters, and physical function in a healthy cohort of Danish men and women across the lifespan.METHODS: Volunteers aged 20-93 years from the Copenhagen City Heart Study were invited to establish a Danish reference material (Copenhagen Sarcopenia Study) on lean mass characteristics [appendicular lean mass (ALM), iDXA, GE Lunar], muscle function [handgrip strength (HGS), Jamar dynamometer and leg extension power (LEP), Nottingham Power Rig], and physical function [30 s sit-to-stand test (STS), 10-m maximal and habitual gait speed (GS)].RESULTS: A total of 1305 participants [729 women (age: 56.4 ± 18.9 years, height: 1.66 ± 0.01 m, body mass index: 24.6 ± 4.3 kg/m2 and 576 men, age: 57.0 ± 17.5 years, height: 1.80 ± 0.07 m, body mass index: 26.0 ± 3.9 kg/m2 ] completed all measurements and were included in the present analysis. Lean mass characteristics (TLM, ALM, and ALM/h2 ) decreased with increasing age in both men and women (P < 0.001). Men demonstrated larger absolute and relative total ALM and higher HGS and LEP compared with women at all age intervals (P < 0.001). HGS and LEP decreased progressively with age in both men and women (P < 0.01); 30 s STS performance, habitual GS, and maximal GS decreased at an accellerated rate of decline with increasing age in both men and women (P < 0.001). Habitual GS was reduced in men and women aged ≥70 years, while maximal GS was reduced from the age of ≥60 years compared with young adults (P < 0.001). Regardless of sex, 30 s STS was reduced from the age of ≥50 years compared with the young refer