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1.
Cardiovasc Res ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38739545

ABSTRACT

BACKGROUND: Obesity and type 2 diabetes (T2D) are major risk factors for cardiovascular diseases (CVD). Dysregulated pro-apoptotic ceramide synthesis reduces ß-cell insulin secretion, thereby promoting hyperglycemic states which may manifest as T2D. Pro-apoptotic ceramides modulate insulin sensitivity and glucose tolerance while being linked to poor cardiovascular outcomes. Sirtuin-1 (SIRT1) is a NAD + - dependent deacetylase that protects against pancreatic ß-cell dysfunction; however, systemic levels are decreased in obese T2D mice and may promote pro-apoptotic ceramide synthesis and hyperglycemia. Herein, we aimed to assess the effects of restoring circulating SIRT1 levels to prevent metabolic imbalance in obese and diabetic mice. METHODS AND RESULTS: Circulating SIRT1 levels were reduced in obese diabetic mice (db/db) as compared to age-matched non-diabetic db/+ controls. Restoration of SIRT1 plasma levels with recombinant murine SIRT1 for 4-weeks prevented body weight gain, improved glucose tolerance, insulin sensitivity and vascular function in mice models of obesity and T2D. Untargeted lipidomics revealed that SIRT1 restored insulin-secretory function of ß-cells by reducing synthesis and accumulation of pro-apoptotic ceramides. Molecular mechanisms involved direct binding to and deacetylation of Toll-like receptor 4 (TLR4) by SIRT1 in ß-cells thereby decreasing the rate limiting enzymes of sphingolipid synthesis SPTLC1/2 via AKT/NF-κB. Among T2D patients, those with high baseline plasma levels of SIRT1 prior to metabolic surgery displayed restored ß-cell function (HOMA2- ß) and were more likely to have T2D remission during follow-up. CONCLUSION: Acetylation of TLR4 promotes ß-cell dysfunction via ceramide synthesis in T2D, which is blunted by systemic SIRT1 replenishment. Hence, restoration of systemic SIRT1 may provide a novel therapeutic strategy to counteract toxic ceramide synthesis and mitigate cardiovascular complications of T2D.

2.
Diabetes Obes Metab ; 26(3): 1023-1032, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38092710

ABSTRACT

AIM: To assess weight loss associated with liraglutide 3.0 mg treatment in individuals with obesity (body mass index [BMI] ≥30 kg/m2 ) or overweight (BMI > 27 to <30 kg/m2 ) in a reimbursed, real-world setting in Switzerland. MATERIALS AND METHODS: ADDRESS was a non-comparative, multicentre, retrospective exposure cohort study in Switzerland, examining weight loss in individuals with obesity or overweight whose treatment was reimbursed (divided into BMI subgroups) or non-reimbursed. The primary outcomes were proportions of participants in the reimbursed cohort achieving predefined weight loss targets with liraglutide 3.0 mg at Week 16 (≥5% and ≥7% for the lower BMI [28 to <35 kg/m2 with weight-related comorbidities] and higher BMI [≥35 kg/m2 ] subgroups, respectively) and Month 10 (additional ≥5% from Week 16; per Swiss reimbursement criteria). RESULTS: The full analysis set comprised 258 individuals (195 reimbursed; 63 non-reimbursed). In the reimbursed cohort, 139 individuals (71.3%) achieved their weight loss targets at Week 16. Of individuals who met the Week-16 criteria, 43.2% attained an additional 5% weight loss at Month 10. In 162 individuals for whom data were recorded at Month 10, the mean (standard deviation) relative weight loss from baseline to Month 10 was -12.4% (6.4%). CONCLUSIONS: Although reimbursement criteria may be difficult to achieve, particularly the additional weight loss of 5% from Week 16 to Month 10, a clinically relevant overall weight loss from baseline to Month 10 was shown in most individuals with obesity or overweight who received liraglutide 3.0 mg.


Subject(s)
Liraglutide , Overweight , Adult , Humans , Liraglutide/therapeutic use , Overweight/complications , Overweight/drug therapy , Overweight/epidemiology , Switzerland/epidemiology , Retrospective Studies , Cohort Studies , Obesity/drug therapy , Obesity/epidemiology , Weight Loss
3.
Ther Umsch ; 80(6): 280-283, 2023 Aug.
Article in German | MEDLINE | ID: mdl-37855532

ABSTRACT

INTRODUCTION: Endocrinological or metabolic disorders often affect a wide variety of functions of the organism. This can also include an impairment of respiratory function. Diabetic ketoacidosis as a result of insulin deficiency is a typical metabolic acidosis, which the body tries to compensate by an increased exhalation of carbon dioxide. This leads to the classic picture of "Kussmaul" breathing. Due to the increased use of SGLT2 inhibitors, which can reduce the otherwise typical hyperglycemia and thus complicate diagnosis, the occurrence of diabetic ketoacidosis has remained an important differential diagnosis in recent years. Pathologies of the thyroid gland can lead to dyspnea not only by morphological changes, for example in the case of goiter (compression). Functional disorders must also be considered here. Both hypo- and hyperthyroidism affect the cardiovascular system in different ways and may ultimately lead to the clinical picture of dyspnea. If the corresponding entities are thought of, the laboratory diagnosis of the aforementioned metabolic/endocrinological disorders is then basically straightforward. Accordingly, knowledge of these disorders as a differential diagnosis of tachy- and dyspnea is important.


Subject(s)
Acidosis , Diabetic Ketoacidosis , Hyperglycemia , Humans , Diabetic Ketoacidosis/diagnosis , Diabetic Ketoacidosis/therapy , Diabetic Ketoacidosis/complications , Acidosis/complications , Acidosis/diagnosis , Hyperglycemia/complications , Insulin , Dyspnea/diagnosis , Dyspnea/etiology
4.
Front Nutr ; 10: 1255499, 2023.
Article in English | MEDLINE | ID: mdl-37810925

ABSTRACT

Accurate dietary assessment is crucial for nutrition and health research. Traditional methods, such as food records, food frequency questionnaires, and 24-hour dietary recalls (24HR), have limitations, such as the need for trained interviewers, time-consuming procedures, and inaccuracies in estimations. Novel technologies, such as image-based dietary assessment apps, have been developed to overcome these limitations. SNAQ is a novel image-based food-recognition app which, based on computer vision, assesses food type and volume, and provides nutritional information about dietary intake. This cross-sectional observational study aimed to investigate the validity of SNAQ as a dietary assessment tool for measuring energy and macronutrient intake in adult women with normal body weight (n = 30), compared to doubly labeled water (DLW), a reference method for total daily energy expenditure (TDEE). Energy intake was also estimated using a one-day 24HR for direct comparison. Bland-Altman plots, paired difference tests, and Pearson's correlation coefficient were used to assess agreement and relationships between the methods. SNAQ showed a slightly higher agreement (bias = -329.6 kcal/day) with DLW for total daily energy intake (TDEI) compared to 24HR (bias = -543.0 kcal/day). While both SNAQ and 24HR tended to underestimate TDEI, only 24HR significantly differed from DLW in this regard (p < 0.001). There was no significant relationship between estimated TDEI and TDEE using SNAQ (R2 = 27%, p = 0.50) or 24HR (R2 = 34%, p = 0.20) and there were no significant differences in energy and macronutrient intake estimates between SNAQ and 24HR (Δ = 213.4 kcal/day). In conclusion, these results indicate that SNAQ provides a closer representation of energy intake in adult women with normal body weight than 24HR when compared to DLW, but no relationship was found between the energy estimates of DLW and of the two dietary assessment tools. Further research is needed to determine the clinical relevance and support the implementation of SNAQ in research and clinical settings. Clinical trial registration: This study is registered on ClinicalTrials.gov with the unique identifier NCT04600596 (https://clinicaltrials.gov/ct2/show/NCT04600596).

5.
Sens Diagn ; 2(4): 918-928, 2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37465007

ABSTRACT

Non-invasive breath analysis with mobile health devices bears tremendous potential to guide therapeutic treatment and personalize lifestyle changes. Of particular interest is the breath volatile acetone, a biomarker for fat burning, that could help in understanding and treating metabolic diseases. Here, we report a hand-held (6 × 10 × 19.5 cm3), light-weight (490 g), and simple device for rapid acetone detection in breath. It comprises a tailor-made end-tidal breath sampling unit, connected to a sensor and a pump for on-demand breath sampling, all operated using a Raspberry Pi microcontroller connected with a HDMI touchscreen. Accurate acetone detection is enabled by introducing a catalytic filter and a separation column, which remove and separate undesired interferents from acetone upstream of the sensor. This way, acetone is detected selectively even in complex gas mixtures containing highly concentrated interferents. This device accurately tracks breath acetone concentrations in the exhaled breath of five volunteers during a ketogenic diet, being as high as 26.3 ppm. Most importantly, it can differentiate small acetone changes during a baseline visit as well as before and after an exercise stimulus, being as low as 0.5 ppm. It is stable for at least four months (122 days), and features excellent bias and precision of 0.03 and 0.6 ppm at concentrations below 5 ppm, as validated by proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF-MS). Hence, this detector is highly promising for simple-in-use, non-invasive, and routine monitoring of acetone to guide therapeutic treatment and track lifestyle changes.

6.
Lancet Diabetes Endocrinol ; 11(9): 675-693, 2023 09.
Article in English | MEDLINE | ID: mdl-37524103

ABSTRACT

Viruses have been present during all evolutionary steps on earth and have had a major effect on human history. Viral infections are still among the leading causes of death. Another public health concern is the increase of non-communicable metabolic diseases in the last four decades. In this Review, we revisit the scientific evidence supporting the presence of a strong bidirectional feedback loop between several viral infections and metabolic diseases. We discuss how viruses might lead to the development or progression of metabolic diseases and conversely, how metabolic diseases might increase the severity of a viral infection. Furthermore, we discuss the clinical relevance of the current evidence on the relationship between viral infections and metabolic disease and the present and future challenges that should be addressed by the scientific community and health authorities.


Subject(s)
Metabolic Diseases , Virus Diseases , Humans , Clinical Relevance , Virus Diseases/complications , Metabolic Diseases/epidemiology , Public Health
7.
Diabetes Technol Ther ; 25(7): 467-475, 2023 07.
Article in English | MEDLINE | ID: mdl-37093196

ABSTRACT

Aims: To investigate the effect of empagliflozin on glucose dynamics in individuals suffering from postbariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). Methods: Twenty-two adults with PBH after RYGB were randomized to empagliflozin 25 mg or placebo once daily over 20 days in a randomized, double-blind, placebo-controlled, crossover trial. The primary efficacy outcome was the amplitude of plasma glucose excursion (peak to nadir) during a mixed-meal tolerance test (MMTT). Outcomes of the outpatient period were assessed using continuous glucose monitoring (CGM) and an event-tracking app. Results: The amplitude of glucose excursion during the MMTT was 8.1 ± 2.4 mmol/L with empagliflozin versus 8.1 ± 2.6 mmol/L with placebo (mean ± standard deviation, P = 0.807). CGM-based mean amplitude of glucose excursion during the 20-day period was lower with empagliflozin than placebo (4.8 ± 1.3 vs. 5.2 ± 1.6. P = 0.028). Empagliflozin reduced the time spent with CGM values >10.0 mmol/L (3.8 ± 3.5% vs. 4.7 ± 3.8%, P = 0.009), but not the time spent with CGM values <3.0 mmol/L (1.7 ± 1.6% vs. 1.5 ± 1.5%, P = 0.457). No significant difference was observed in the quantity and quality of recorded symptoms. Eleven adverse events occurred with empagliflozin (three drug-related) and six with placebo. Conclusions: Empagliflozin 25 mg reduces glucose excursions but not hypoglycemia in individuals with PBH. Clinical Trial Registration: Clinicaltrials.gov: NCT05057819.


Subject(s)
Gastric Bypass , Hypoglycemia , Adult , Humans , Gastric Bypass/adverse effects , Blood Glucose , Blood Glucose Self-Monitoring , Cross-Over Studies , Hypoglycemia/drug therapy , Hypoglycemia/etiology , Hypoglycemia/prevention & control , Glucose , Double-Blind Method
8.
J Endocrinol ; 257(2)2023 05 01.
Article in English | MEDLINE | ID: mdl-36753292

ABSTRACT

Despite the existence of numerous studies supporting a pathological link between fructose consumption and the development of the metabolic syndrome and its sequelae, such as non-alcoholic fatty liver disease (NAFLD), this link remains a contentious issue. With this article, we shed a light on the impact of sugar/fructose intake on hepatic de novo lipogenesis (DNL), an outcome parameter known to be dysregulated in subjects with type 2 diabetes and/or NAFLD. In this review, we present findings from human intervention studies using physiological doses of sugar as well as mechanistic animal studies. There is evidence from both human and animal studies that fructose is a more potent inducer of hepatic lipogenesis than glucose. This is most likely due to the liver's prominent physiological role in fructose metabolism, which may be disrupted under pathological conditions by increased hepatic expression of fructolytic and lipogenic enzymes. Increased DNL may not only contribute to ectopic fat deposition (i.e. in the liver), but it may also impair several metabolic processes through DNL-related fatty acids (e.g. beta-cell function, insulin secretion, or insulin sensitivity).


Subject(s)
Diabetes Mellitus, Type 2 , Non-alcoholic Fatty Liver Disease , Animals , Humans , Non-alcoholic Fatty Liver Disease/metabolism , Fructose/adverse effects , Lipogenesis/physiology , Diabetes Mellitus, Type 2/metabolism , Liver/metabolism
9.
Clin Obes ; 13(1): e12561, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36239531

ABSTRACT

Previous data from short term studies have shown an efficacy of the duodenal-jejunal bypass liner (DJBL) for weight loss. However, less data is available regarding weight change after device removal and possible predictors for weight loss. This is a retrospective chart review of all patients who had DJBL inserted at the University Hospital Zurich between December 2012 and June 2015. A total of 27 patients had DJBL insertion. The median BMI at baseline was 38.5 (34.0-42.2) kg/m2 . In the 24 patients with DJBL treatment >3 months (failed implantation or early removal due to side effects in 3 patients), the mean duration of implantation was 42.9 ± 13.1 weeks. During the treatment, the mean total body weight loss (%TBWL) was 15.0 ± 8.3%. Fifteen patients had long-term follow-up data available (mean duration of follow-up 4.0 ± 0.9 years). The mean weight change was 12.7 ± 12.8 kg, corresponding with a mean % weight regain of 13.3 ± 13.3%. Five patients (33.3%) subsequently underwent bariatric surgery. In patients with class I obesity (BMI <35 kg/m2 at baseline), 4 out of 6 (66.7%) had a stable weight or only a weight regain <7%. In contrast, no patient with BMI >35 kg/m2 at baseline was able to keep weight regain below 7%. DJBL is an effective treatment for obesity, but substantial weight regain occurs during long-term follow up after the device removal, in particular in patients with BMI > 35 kg/m2 .


Subject(s)
Bariatric Surgery , Diabetes Mellitus, Type 2 , Obesity, Morbid , Humans , Duodenum/surgery , Jejunum/surgery , Body Mass Index , Retrospective Studies , Follow-Up Studies , Obesity, Morbid/surgery , Diabetes Mellitus, Type 2/surgery , Prospective Studies , Obesity/etiology , Treatment Outcome , Bariatric Surgery/adverse effects , Weight Loss , Weight Gain
10.
Clin Nutr ESPEN ; 52: 445-449, 2022 12.
Article in English | MEDLINE | ID: mdl-36513485

ABSTRACT

BACKGROUND & AIMS: Advances in technology enable patients on home parenteral nutrition (HPN) to manage their treatment more independently and safely. eHealth is a promising application of electronic means in healthcare, aimed at improving and simplifying processes and connecting the different parties involved. A thorough understanding of the attitudes and expectations of patients on HPN towards eHealth is a prerequisite for a successful implementation. However, to the best of our knowledge, such a survey preceding the implementation of HPN specific eHealth care has never been conducted. The objective of this preliminary survey is the acquisition of insights on the attitudes and expectations of patients on HPN towards eHealth. Resulting findings then serve as the basis for the design of an eHealth platform to facilitate communication among those involved in HPN care, improve the HPN management, and safeguard and monitor the treatment. METHODS: We conducted a survey on the attitudes and expectations of patients towards an envisioned eHealth platform for HPN. Patients were recruited from large Swiss hospitals by their treating physician or directly by the research team. The surveys were conducted between September 2020 and October 2021 by structured personal interviews based on a questionnaire. RESULTS: We included 35 patients on HPN (21 [60%] females) treated in ambulant care of 4 hospitals. They had a median (interquartile range) age of 55 (18) years and a median (interquartile range) duration of parenteral nutrition of 1.3 (3.1) years. Most patients (n = 30, 86%) were equipped with a smartphone, tablet, or computer and 22 (63%) used apps and rated themselves as proficient with the corresponding digital device. A majority of patients rated the following aspects and features of the platform as important: Data collection and storage (n = 29, 83%), checklists for PN, catheter, and infusion pump handling (n = 28, 80%), video instructions (n = 27, 77%), and videoconferencing with physicians (n = 25, 71%). Most patients (n = 26, 74%) were willing to enter data into the platform themselves. The type of data to be entered should be defined on an individual basis. CONCLUSIONS: Patients on HPN are open to videoconference consultations and using an eHealth platform. Two-thirds have the necessary technical skills including suitable digital devices for an eHealth care. We identified key features of an eHealth platform to improve HPN management.


Subject(s)
Parenteral Nutrition, Home , Telemedicine , Female , Humans , Infant , Male , Attitude , Motivation , Surveys and Questionnaires
11.
Nutrients ; 14(19)2022 Oct 07.
Article in English | MEDLINE | ID: mdl-36235821

ABSTRACT

Human fibroblast growth factor 21 (FGF21) is a multifaceted metabolic regulator considered to control sugar intake and to exert beneficial effects on glucose and lipid metabolism. Elevated serum FGF21 levels are associated with metabolic syndrome, suggesting a state of FGF21 resistance. Further, given the evidence of a hepatic ChREBP and FGF21 signaling axis, it can be assumed that SSBs containing fructose would possibly increase FGF21 concentrations. We investigated the effects of sugar-sweetened beverage (SSB) consumption on fasting FGF21 levels in healthy, lean men, discriminating the effects of glucose, fructose, and their disaccharide sucrose by secondary data analysis from a randomized controlled trial. Seven weeks of daily SSB consumption resulted in increased fasting FGF21 in healthy, lean men, irrespective of the sugar type. Medians of ΔFGF21 between post-SSB intervention values (week 7) and no-intervention period values (IQR) in pg/mL were: glucose 17.4 (0.4-45.8), fructose 22.9 (-8.6-35.1), and sucrose 13.7 (2.2-46.1). In contrast, this change in FGF21 concentration was only 6.3 (-20.1-26.9) pg/mL in the control group. The lack of a fructose-specific effect on FGF21 concentrations is contrary to our assumption. It is concluded that SSB intake may impact FGF21 concentrations and could contribute to the increased FGF21 concentrations observed in subjects suffering from metabolic syndrome that is possibly associated with decreased FGF21 responsiveness.


Subject(s)
Metabolic Syndrome , Sugar-Sweetened Beverages , Beverages , Fasting , Fibroblast Growth Factors , Fructose/adverse effects , Glucose/metabolism , Humans , Male , Metabolic Syndrome/etiology , Sucrose/adverse effects , Sugar-Sweetened Beverages/adverse effects , Sugars
12.
Horm Metab Res ; 54(8): 522-531, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35468630

ABSTRACT

Coronavirus disease 2019 (COVID-19) is characterized by a wide clinical spectrum that includes abnormalities in liver function indicative of liver damage. Conversely, people with liver diseases are at higher risk of severe COVID-19. In the current review, we summarize first the epidemiologic evidence describing the bidirectional relationship between COVID-19 and liver function/liver diseases. Additionally, we present the most frequent histologic findings as well as the most important direct and indirect mechanisms supporting a COVID-19 mediated liver injury. Furthermore, we focus on the most frequent liver disease in the general population, non-alcoholic or metabolic-associated fatty liver disease (NAFLD/MAFLD), and describe how COVID-19 may affect NAFLD/MAFLD development and progression and conversely how NAFLD/MAFLD may further aggravate a COVID-19 infection. Finally, we present the long-term consequences of the pandemic on the development and management of NAFLD.


Subject(s)
COVID-19 , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Pandemics , Risk Factors
13.
J Endocrinol ; 253(1): 1-11, 2022 02 11.
Article in English | MEDLINE | ID: mdl-35017316

ABSTRACT

Pancreatic ß-cells depend on the well-balanced regulation of cytosolic zinc concentrations, providing sufficient zinc ions for the processing and storage of insulin, but avoiding toxic effects. The zinc transporter ZnT8, encoded by SLC30A8,is a key player regarding islet cell zinc homeostasis, and polymorphisms in this gene are associated with altered type 2 diabetes susceptibility in man. The objective of this study was to investigate the role of ZnT8 and zinc in situations of cellular stress as hypoxia or inflammation. Isolated islets of WT and global ZnT8-/- mice were exposed to hypoxia or cytokines and cell death was measured. To explore the role of changing intracellular Zn2+ concentrations, WT islets were exposed to different zinc concentrations using zinc chloride or the zinc chelator N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN). Hypoxia or cytokine (TNF-α, IFN-γ, IL1-ß) treatment induced islet cell death, but to a lesser extent in islets from ZnT8-/- mice, which were shown to have a reduced zinc content. Similarly, chelation of zinc with TPEN reduced cell death in WT islets treated with hypoxia or cytokines, whereas increased zinc concentrations aggravated the effects of these stressors. This study demonstrates a reduced rate of cell death in islets from ZnT8-/- mice as compared to WT islets when exposed to two distinct cellular stressors, hypoxia or cytotoxic cytokines. This protection from cell death is, in part, mediated by a reduced zinc content in islet cells of ZnT8-/- mice. These findings may be relevant for altered diabetes burden in carriers of risk SLC30A8 alleles in man.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease/genetics , Islets of Langerhans/metabolism , Zinc Transporter 8/genetics , Animals , Apoptosis/genetics , Cell Death/drug effects , Cell Death/genetics , Cell Hypoxia , Cell Line , Cell Proliferation/genetics , Cells, Cultured , Cytokines/pharmacology , Diabetes Mellitus, Type 2/metabolism , Female , Insulin Secretion/drug effects , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Confocal , Zinc/metabolism , Zinc/pharmacology , Zinc Transporter 8/metabolism
15.
J Hepatol ; 75(1): 46-54, 2021 07.
Article in English | MEDLINE | ID: mdl-33684506

ABSTRACT

BACKGROUND & AIMS: Excessive fructose intake is associated with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. We aimed to determine whether fructose elicits specific effects on lipid metabolism independently of excessive caloric intake. METHODS: A total of 94 healthy men were studied in this double-blind, randomized trial. They were assigned to daily consumption of sugar-sweetened beverages (SSBs) containing moderate amounts of fructose, sucrose (fructose-glucose disaccharide) or glucose (80 g/day) in addition to their usual diet or SSB abstinence (control group) for 7 weeks. De novo fatty acid (FA) and triglyceride synthesis, lipolysis and plasma free FA (FFA) oxidation were assessed by tracer methodology. RESULTS: Daily intake of beverages sweetened with free fructose and fructose combined with glucose (sucrose) led to a 2-fold increase in basal hepatic fractional secretion rates (FSR) compared to control (median FSR %/day: sucrose 20.8 (p = 0.0015); fructose 19.7 (p = 0.013); control 9.1). Conversely, the same amounts of glucose did not change FSR (median of FSR %/day 11.0 (n.s.)). Fructose intake did not change basal secretion of newly synthesized VLDL-triglyceride, nor did it alter rates of peripheral lipolysis, nor total FA and plasma FFA oxidation. Total energy intake was similar across groups. CONCLUSIONS: Regular consumption of both fructose- and sucrose-sweetened beverages in moderate doses - associated with stable caloric intake - increases hepatic FA synthesis even in a basal state; this effect is not observed after glucose consumption. These findings provide evidence of an adaptative response to regular fructose exposure in the liver. LAY SUMMARY: This study investigated the metabolic effects of daily sugar-sweetened beverage consumption for several weeks in healthy lean men. It revealed that beverages sweetened with the sugars fructose and sucrose (glucose and fructose combined), but not glucose, increase the ability of the liver to produce lipids. This change may pave the way for further unfavorable effects on metabolic health. CLINICAL TRIAL REGISTRATION NUMBER: NCT01733563.


Subject(s)
Fatty Acids/biosynthesis , Fructose , Glucose , Lipogenesis , Lipoproteins, VLDL/biosynthesis , Liver , Sucrose , Triglycerides/biosynthesis , Adult , Double-Blind Method , Energy Intake , Fructose/administration & dosage , Fructose/adverse effects , Fructose/metabolism , Glucose/administration & dosage , Glucose/metabolism , Healthy Volunteers , Humans , Lipid Metabolism/drug effects , Lipid Metabolism/physiology , Lipogenesis/drug effects , Lipogenesis/physiology , Liver/drug effects , Liver/metabolism , Male , Sucrose/administration & dosage , Sucrose/adverse effects , Sucrose/metabolism , Sugar-Sweetened Beverages , Sweetening Agents/pharmacology
16.
Anal Chem ; 93(2): 1170-1178, 2021 01 19.
Article in English | MEDLINE | ID: mdl-33315383

ABSTRACT

Methanol poisoning outbreaks after consumption of adulterated alcohol frequently overwhelm health care facilities in developing countries. Here, we present how a recently developed low-cost and handheld breath detector can serve as a noninvasive and rapid diagnostic tool for methanol poisoning. The detector combines a separation column and a micromachined chemoresistive gas sensor fully integrated into a device that communicates wirelessly with a smartphone. The performance of the detector is validated with methanol-spiked breath of 20 volunteers (105 breath samples) after consumption of alcoholic beverages. Breath methanol concentrations were quantified accurately within 2 min in the full breath-relevant range (10-1000 ppm) in excellent agreement (R2 = 0.966) with benchtop mass spectrometry. Bland-Altman analysis revealed sufficient limits of agreement (95% confidence intervals), promising to indicate reliably the clinical need for antidote and hemodialysis treatment. This simple-in-use detector features high diagnostic capability for accurate measurement of methanol in spiked breath, promising for rapid screening of methanol poisoning and assessment of severity. It can be applied readily by first responders to distinguish methanol from ethanol poisoning and monitor in real time the subsequent hospital treatment.


Subject(s)
Breath Tests , Methanol/analysis , Humans , Spectroscopy, Fourier Transform Infrared
17.
J Breath Res ; 15(1): 016006, 2020 10 31.
Article in English | MEDLINE | ID: mdl-32957090

ABSTRACT

Exhaled breath acetone (BrAce) was investigated during and after submaximal aerobic exercise as a volatile biomarker for metabolic responsiveness in high and lower-fit individuals in a prospective cohort pilot-study. Twenty healthy adults (19-39 years) with different levels of cardiorespiratory fitness (VO2peak), determined by spiroergometry, were recruited. BrAce was repeatedly measured by proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) during 40-55 min submaximal cycling exercise and a post-exercise period of 180 min. Activity of ketone and fat metabolism during and after exercise were assessed by indirect calorimetric calculation of fat oxidation rate and by measurement of venous ß-hydroxybutyrate (ßHB). Maximum BrAce ratios were significantly higher during exercise in the high-fit individuals compared to the lower-fit group (t-test; p= 0.03). Multivariate regression showed 0.4% (95%-CI = -0.2%-0.9%, p= 0.155) higher BrAce change during exercise for every ml kg-1 min-1 higher VO2peak. Differences of BrAce ratios during exercise were similar to fat oxidation rate changes, but without association to respiratory minute volume. Furthermore, the high-fit group showed higher maximum BrAce increase rates (46% h-1) in the late post-exercise phase compared to the lower-fit group (29% h-1). As a result, high-fit young, healthy individuals have a higher increase in BrAce concentrations related to submaximal exercise than lower-fit subjects, indicating a stronger exercise-related activation of fat metabolism.


Subject(s)
Acetone/analysis , Breath Tests/methods , Cardiorespiratory Fitness/physiology , Exercise/physiology , 3-Hydroxybutyric Acid/blood , Adult , Exhalation , Female , Humans , Ketone Bodies/metabolism , Male , Oxidation-Reduction , Oxygen Consumption/physiology , Pilot Projects , Prospective Studies , Young Adult
19.
ACS Sens ; 4(2): 268-280, 2019 02 22.
Article in English | MEDLINE | ID: mdl-30623644

ABSTRACT

Breath sensors can revolutionize medical diagnostics by on-demand detection and monitoring of health parameters in a noninvasive and personalized fashion. Despite extensive research for more than two decades, however, only a few breath sensors have been translated into clinical practice. Actually, most never even left the scientific laboratories. Here, we describe key challenges that currently impede realization of breath sensors and highlight strategies to overcome them. Specifically, we start with breath marker selection (with emphasis on metabolic and inflammatory markers) and breath sampling. Next, the sensitivity, stability, and selectivity requirements for breath sensors are described. Concepts are elaborated to systematically address these requirements by material design (focusing on chemoresistive metal oxides), orthogonal arrays, and filters. Finally, aspects of portable device integration, user communication, and clinical applicability are discussed.


Subject(s)
Breath Tests/instrumentation , Health , Monitoring, Physiologic/instrumentation , Equipment Design , Humans
20.
Obes Surg ; 29(3): 928-934, 2019 03.
Article in English | MEDLINE | ID: mdl-30610674

ABSTRACT

BACKGROUND: Bariatric surgery (BS) has been shown to ameliorate health-related quality of life and eating disorder symptoms. However, the correlation of these changes with weight loss is not uniform, suggesting that additional factors have an impact on postoperative outcomes. OBJECTIVE: To assess the impact of BS on eating disorder symptoms at 1 year postoperatively and to generate predictive models for the achievement of optimal eating behavior. METHODS: Retrospective cohort study on a prospectively collected database of all consecutive patients who underwent primary BS in our academic center between January 2015 and March 2017. Eating Disorder Examination-Questionnaire (EDE-Q) was used to measure eating psychopathology. Logistic regression was used to estimate the odds ratio of achieving "healthy" EDE-Q at 1 year. Missing data was handled by multiple imputations for the regression model. RESULTS: Two-hundred thirty-four patients were included. A complete-case analysis in 135 cases showed a "healthy" EDE-Q in 27.4% at baseline and in 83.7% at 1 year (difference = 56.3%, P = 0.018). Only the baseline EDE-Q "healthy" status influenced significantly the odds of achieving "healthy" EDE-Q at 1 year (OR 6.7, 95% CI 1.18-38.14, P = 0.04). CONCLUSION: BS seems to promote successful treatment of self-reported eating disorder symptoms during the first postoperative year. The achievement of optimal results is independent of age, sex, weight loss, obesity-related comorbidity status, surgical technique, or 30-day surgical complications. Future studies, using validated questionnaires specifically designed to investigate eating behavior after BS and/or direct measurements of the eating behavior are needed to clarify the underlying neuropsychologic mechanisms that drive the observed postoperative changes.


Subject(s)
Bariatric Surgery , Feeding and Eating Disorders/diagnosis , Feeding and Eating Disorders/surgery , Obesity, Morbid/psychology , Obesity, Morbid/surgery , Adult , Feeding Behavior , Feeding and Eating Disorders/complications , Female , Health Status Indicators , Humans , Male , Middle Aged , Obesity, Morbid/complications , Quality of Life , Retrospective Studies , Self Report , Treatment Outcome , Weight Loss
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