Hypoglycemia after Bariatric Surgery in Mice and Optimal Dosage and Efficacy of Glucose Supplementation

The Roux-en-Y Gastric Bypass (RYGB) mouse model is a vital tool for studying the pathophysiology of bariatric surgery and contributes greatly to research on obesity and diabetes. However, complications including postsurgical hypoglycemia can have profoundly negative effects. Unlike in humans, blood glucose (BG) is not typically managed in postoperative rodents, despite their critical role as translational models; without this management, rodents can experience hypoglycemia, potentially impairing wound healing, decreasing survivability, complicating interpretation of research data, and limiting translational utility. In this project, we sought to identify an optimal method for minimally invasive administration of dextrose in C57BL/6N (n = 16; 8 male, 8 female) mice. To do so, we characterized BG pharmacokinetic profiles after subcutaneous and oral–transmucosal (OTM) administration of dextrose. Compared with OTM dosage, the subcutaneous route provided more consistent and reliable delivery of glucose and did not cause significant adverse reactions. We then evaluated the frequency of hypoglycemic events after RYGB in C57BL/6N mice (n = 16; 8 male, 8 female) and the effects of subcutaneous dextrose supplementation on morbidity and mortality. BG measurement and behavioral pain assessment (grimace test) were performed for 3 d after surgery. Hypoglycemic (BG ≤ 60 mg/dL) animals were assigned to dose (5% dextrose SC) or no-dose treatment groups. Nearly all (87%) mice became hypoglycemic; 2 of these mice died. No significant intergroup difference in grimace score or mortality was detected. Overall, our results demonstrate that hypoglycemia is a frequent adverse event after RYGB in mice and that subcutaneous injection of dextrose is a safe and effective way to manage hypoglycemia. Further studies are necessary to optimize the intervention threshold and optimal dosage; regardless, we recommend glycemic management after RYGB surgery in mice.

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Preoperative Cardiac Diagnostics in Bariatric Patients with Diabetes and Perioperative Morbidity: Results of a Cohort of 258 Patients

Obesity Surgery ◽

10.1007/s11695-021-05300-5 ◽

2021 ◽

Author(s):

Benjamin Stillhard ◽

B. T. Truc Ngo ◽

Ralph Peterli ◽

Thomas Peters ◽

Romano Schneider ◽

...

Keyword(s):

Bariatric Surgery ◽

Myocardial Perfusion ◽

Cardiac Catheterization ◽

Myocardial Perfusion Scintigraphy ◽

Perfusion Scintigraphy ◽

Perioperative Morbidity ◽

Obesity And Diabetes ◽

Patients With Diabetes ◽

Cardiac Assessment ◽

Bariatric Patients

Abstract Purpose The combination of obesity and diabetes mellitus are well-known risk factors for cardiovascular complications and perioperative morbidity in metabolic surgery. The aim of this study was to evaluate effectivity and reliability of the cardiac assessment in patients with diabetes prior to bariatric surgery. Setting Private, university-affiliated teaching hospital, Switzerland Material and Methods Retrospective analysis of prospectively collected data on results and consequences of cardiac assessments in 258 patients with obesity and diabetes scheduled for primary bariatric surgery at our institution between January 2010 and December 2018. Results Out of 258 patients, 246 (95.3%) received cardiac diagnostics: 173 (67.1%) underwent stress-rest myocardial perfusion scintigraphy (MPS), 15 (5.8%) patients had other cardiac imaging including cardiac catheterization, 58 (22.5%) patients had echocardiography and/or stress electrocardiography, and 12 (4.7%) patients received no cardiac evaluation. Subsequently, cardiac catheterization was performed in 28 patients (10.9%), and coronary heart disease was detected and treated in 15 subjects (5.8%). Of these 15 individuals, 5 (33.3%) patients had diffuse vascular sclerosis, 8 (53.3%) patients underwent coronary angioplasty and stenting, and 2 (13.3%) patients coronary artery bypass surgery. Bariatric surgery was performed without perioperative cardiovascular events in all 258 patients. Conclusion Our data suggest that a detailed cardiac assessment is mandatory in bariatric patients with diabetes to identify those with yet unknown cardiovascular disease before performing bariatric surgery. We recommend carrying out myocardial perfusion scintigraphy as a reliable diagnostic tool in this vulnerable population. If not viable, stress echocardiography should be performed as a minimum.

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Octanoic acid a major component of widely consumed medium-chain triglyceride ketogenic diet is detrimental to bone

Scientific Reports ◽

10.1038/s41598-021-86468-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shreshta Jain ◽

Reena Rai ◽

Divya Singh ◽

Divya Vohora

Keyword(s):

Bone Loss ◽

Ketogenic Diet ◽

Octanoic Acid ◽

Bone Microarchitecture ◽

Medium Chain Triglyceride ◽

Decanoic Acid ◽

Clinical Findings ◽

Micro Computed Tomography ◽

Negative Effects ◽

Treatment Groups

AbstractOctanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with decanoic acid. The MCT ketogenic diet is commonly consumed for weight loss but has also showcased neuroprotective potential against neurodegenerative disorders. However, recent clinical findings have reported a critical disadvantage with the long-term consumption of ketogenic diet i.e. bone loss. The following study was employed to investigate whether the two major components of MCT diet also possess bone loss potential as observed with classical ketogenic diet. Swiss albino mice aged between 10 and 12 weeks, were divided into 3 treatment groups that were administered with oral suspensions of octanoic acid, decanoic acid and a combination of both for 4 weeks. Bone specific markers, microarchitectural parameters, using micro computed tomography, and biomechanical strength were analyzed. Remarkably deleterious alterations in the trabecular bone microarchitecture, and on bone markers were observed in the octanoic acid treated groups. Our results suggest significant negative effects on bone health by octanoic acid. These findings require further investigation and validation in order to provide significant clinically relevant data to possibly modify dietary composition of the MCT ketogenic diet.

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Association of Bariatric Surgery With Cancer Incidence in Patients With Obesity and Diabetes: Long-term Results From the Swedish Obese Subjects Study

10.2337/figshare.16903630 ◽

2021 ◽

Author(s):

Kajsa Sjöholm ◽

Lena MS Carlsson ◽

Per-Arne Svensson ◽

Johanna C. Andersson-Assarsson ◽

Felipe Kristensson ◽

...

Keyword(s):

Type 2 Diabetes ◽

Bariatric Surgery ◽

Cancer Risk ◽

Cancer Incidence ◽

Diabetes Remission ◽

Obesity And Diabetes ◽

Obese Subjects

OBJECTIVE Obesity and type 2 diabetes are associated with serious, adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study. RESEARCH DESIGN AND METHODS The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of which underwent bariatric surgery, and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years). RESULTS During follow-up, the incidence rate for first-time cancer was 9.1 per 1000-person-years (95% CI, 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1000-person-years (95% CI, 11.2-17.7) in patients treated with usual obesity care (HRadj=0.63; 95% CI 0.44-0.89, p=0.008). Moreover, surgery was associated with reduced cancer incidence in women (HRadj=0.58; 0.38-0.90, p=0.016), although the sex-treatment interaction was non-significant (p=0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (HRadj=0.40; 95% CI 0.22-0.74, p=0.003). CONCLUSIONS These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes, and that durable diabetes remission is associated with reduced cancer risk.

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Mechanisms and Dynamics in the Interplay of Trust and Distrust: Insights from Project-based Collaboration

Organization Studies ◽

10.1177/01708406211040215 ◽

2021 ◽

pp. 017084062110402

Author(s):

Angelos Kostis ◽

Maria Bengtsson ◽

Malin Harryson Näsholm

Keyword(s):

Critical Role ◽

Negative Effects ◽

Interorganizational Trust ◽

Complex Products ◽

Conceptual Distinction ◽

Interorganizational Projects ◽

Complex Solutions ◽

Behavioral Mechanisms ◽

Organizing Principles

Trust and distrust are two distinct organizing principles that play a critical role in interorganizational projects where highly interdependent organizations collaborate to build tailor-made and technologically-complex solutions. Whereas an emerging body of research has debated the conceptual distinction between trust and distrust, this paper emphasizes the processual nature of trusting and distrusting and the interplay between them. Drawing upon insights from project-based collaboration in a complex products and systems (CoPS) industry, we explore the distinct cognitive and behavioral mechanisms through which trust and distrust work, and orient firms towards optimism and watchfulness in the interaction. Our findings show that trust and distrust can act both as substitutes and complements through three interconnected dynamics—undermining, enabling and compensating. These dynamics develop and recursively interrelate through interfirm interactions within single projects and in the broader network. We conclude by presenting our contributions to interorganizational trust literature and by proposing that the interplay of trust and distrust can have both positive and negative effects on the pursuit of project-based relationships.

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Circadian Mechanisms: Cardiac Ion Channel Remodeling and Arrhythmias

Frontiers in Physiology ◽

10.3389/fphys.2020.611860 ◽

2021 ◽

Vol 11 ◽

Author(s):

Joyce Bernardi ◽

Kelly A. Aromolaran ◽

Hua Zhu ◽

Ademuyiwa S. Aromolaran

Keyword(s):

Heart Failure ◽

Circadian Rhythms ◽

Molecular Mechanisms ◽

Normal Sinus Rhythm ◽

Critical Role ◽

The United States ◽

Therapeutic Interventions ◽

Cellular Mechanisms ◽

Normal Sinus ◽

Obesity And Diabetes

Circadian rhythms are involved in many physiological and pathological processes in different tissues, including the heart. Circadian rhythms play a critical role in adverse cardiac function with implications for heart failure and sudden cardiac death, highlighting a significant contribution of circadian mechanisms to normal sinus rhythm in health and disease. Cardiac arrhythmias are a leading cause of morbidity and mortality in patients with heart failure and likely cause ∼250,000 deaths annually in the United States alone; however, the molecular mechanisms are poorly understood. This suggests the need to improve our current understanding of the underlying molecular mechanisms that increase vulnerability to arrhythmias. Obesity and its associated pathologies, including diabetes, have emerged as dangerous disease conditions that predispose to adverse cardiac electrical remodeling leading to fatal arrhythmias. The increasing epidemic of obesity and diabetes suggests vulnerability to arrhythmias will remain high in patients. An important objective would be to identify novel and unappreciated cellular mechanisms or signaling pathways that modulate obesity and/or diabetes. In this review we discuss circadian rhythms control of metabolic and environmental cues, cardiac ion channels, and mechanisms that predispose to supraventricular and ventricular arrhythmias including hormonal signaling and the autonomic nervous system, and how understanding their functional interplay may help to inform the development and optimization of effective clinical and therapeutic interventions with implications for chronotherapy.

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Multiagonist Unimolecular Peptides for Obesity and Type 2 Diabetes: Current Advances and Future Directions

Clinical Medicine Insights Endocrinology and Diabetes ◽

10.1177/1179551420905844 ◽

2020 ◽

Vol 13 ◽

pp. 117955142090584 ◽

Cited By ~ 3

Author(s):

Annie Hasib

Keyword(s):

Type 2 Diabetes ◽

Bariatric Surgery ◽

Hormone Receptors ◽

Gut Hormones ◽

Metabolic Effects ◽

Therapeutic Approaches ◽

Obesity And Diabetes ◽

Gut Hormone ◽

Prevalence Of Obesity

The ever-increasing prevalence of obesity and Type 2 diabetes has necessitated the development of newer and more effective approaches for achieving efficient glycemic control and weight loss. Conventional treatment methods often result in weight gain, further deteriorating the already impaired metabolic control in people with obesity/Type 2 diabetes. Alleviation of obesity and diabetes achieved after bariatric surgeries highlight the therapeutic importance of gut-brain axis and entails development of more patient-friendly approaches replicating the positive metabolic effects of bariatric surgery. Given the potential involvement of several gut hormones in the success of bariatric surgery, the therapeutic importance of synergistic interaction between these hormones for improved metabolism cannot be ignored. Many unimolecular multiagonist peptides are in preclinical and clinical trials as they maximize the combinatorial metabolic efficacy by concurrent activation of multiple gut hormone receptors. This review summarizes the ongoing developments of multiagonist peptides as novel therapeutic approaches against obesity-diabetes.

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Cognitive Control along the Language Spectrum: From the Typical Bilingual Child to Language Impairment

Seminars in Speech and Language ◽

10.1055/s-0039-1692962 ◽

2019 ◽

Vol 40 (04) ◽

pp. 256-271

Author(s):

Klara Marton ◽

Thorfun Gehebe ◽

Lia Pazuelo

Keyword(s):

Cognitive Control ◽

Language Processing ◽

Language Impairment ◽

Cognitive Skills ◽

Critical Role ◽

Bilingual Children ◽

Interference Control ◽

Negative Effects ◽

Control Functions ◽

Language Deficit

AbstractCognitive control refers to the ability to perform goal-directed behaviors in the presence of other compelling actions or in the face of habitual practices. Cognitive control functions play a critical role in children's language processing and literacy development. In recent years, many clinicians have expanded their assessment and treatment to target specific cognitive skills. Our goal is to provide a review of recent findings on cognitive control functions in children with different language status (i.e., monolingual and bilingual children with and without language impairment). While children with language impairment show performance deficits in specific cognitive functions (e.g., working memory updating and interference control), typically developing bilingual children often outperform their monolingual peers in cognitive control tasks. However, the relationship between bilingualism and cognitive control has been controversial. Several factors that influence these variations are discussed. Given the findings on the joint impact of bilingualism and language impairment on cognitive control functions, we identify conditions in which bilingualism attenuates the negative effects of the language deficit and conditions in which language impairment has a stronger effect than bilingualism. Critical issues of bilingual assessment, suggestions, and future directions are discussed.

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