ResearchPad - weight-loss https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Newborn body composition after maternal bariatric surgery]]> https://www.researchpad.co/article/elastic_article_13862 In pregnancy after Roux-en-Y gastric bypass (RYGB), there is increased risk of low birthweight in the offspring. The present study examined how offspring body composition was affected by RYGB.Material and methodsMother-newborn dyads, where the mothers had undergone RYGB were included. Main outcome measure was neonatal body composition. Neonatal body composition was assessed by dual-energy X-ray absorptiometry scanning (DXA) within 48 hours after birth. In a statistical model offspring born after RYGB were compared with a reference material of offspring and analyses were made to estimate the effect of maternal pre-pregnancy body mass index (BMI), gestational weight gain, parity, gestational age at birth and newborn sex on newborn body composition. Analyses were made to estimate the impact of maternal weight loss before pregnancy and of other effects of bariatric surgery respectively. The study was performed at a university hospital between October 2012 and December 2013.ResultsWe included 25 mother-newborn dyads where the mothers had undergone RYGB and compared them to a reference material of 311 mother-newborn dyads with comparable pre-pregnancy BMI. Offspring born by mothers after RYGB had lower birthweight (335g, p<0.001), fat-free mass (268g, p<0.001) and fat% (2.8%, p<0.001) compared with reference material. Only 2% of the average reduction in newborn fat free mass could be attributed to maternal pre-pregnancy weight loss whereas other effects of RYGB accounted for 98%. Regarding reduction in fat mass 52% was attributed to weight loss and 47% to other effects of surgery.ConclusionOffspring born after maternal bariatric surgery, had lower birthweight, fat-free mass and fat percentage when compared with a reference material. RYGB itself and not the pre-pregnancy weight loss seems to have had the greatest impact on fetal growth. ]]> <![CDATA[SAT-567 Hypertriglyceridem...From Mild to Fatal!... Is Time for Awareness]]> https://www.researchpad.co/article/elastic_article_8800 Hypertriglyceridemia… From mild to fatal! … Is Time for Awareness.

Hypertriglyceridemia can be primary or acquired. High triglycerides are related to complications such as pancreatitis and there is a positive correlation between hypertriglyceridemia and atherosclerotic burden. In this case series we aim to discuss pancreatitis as a hypertriglyceridemia complication and to acknowledge the importance of prevention and management. Is there something we can do to raise awareness and avoid complications as in the cases?

All cases present with chief complaint of epigastric cramp-like abdominal pain, radiating to the back, nausea/vomiting and with highly lipemic blood samples.

38y/o F admitted after been found with lipase 268 U/L (n<60 U/L), amylase 131 U/L (n<100 U/L) and findings of pancreatitis on CT scan. Patient with one-year history of T2DM refers this is the 4th episode of pancreatitis and reports that last time she was told about having triglycerides in 4,000 mg/dL for which she went to her physician that prescribe her Fenofibrate. Patient triglycerides were 7,931 mg/dL (n<199 mg/dL) and found with poorly controlled diabetes with HgbA1c 8.4%. She was properly managed, and triglycerides decrease to 1,309 mg/dL.

31y/o F with elevated lipase (237 U/L, n<60 U/L) and findings of pancreatitis on CT scan was admitted and found with 7,755 mg/dL triglycerides. She refers to have endometriosis for which she uses OCPs for >5years. She develops intractable abdominal pain along with abdominal distension and progress to Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation. She had a prolonged ICU stay and after management triglycerides decrease to 95mg/dL, symptoms resolve, and patient was discharge.

48y/o F with pancreatitis, lipase levels 1,452 U/L, amylase 744 U/L and positive imaging findings. Patient with uncontrolled diabetes (HgbA1c 11.0%) and breast mass s/p lumpectomy for which she used tamoxifen for the last 2 years. Triglycerides 7,444mg/dL on Gemfibrozil started due to previous levels found >4,000 mg/dL on outpatient evaluation. She deteriorates clinically and develops renal failure, abdominal compartment syndrome, respiratory distress and hypotension requiring mechanical ventilation and vasopressors. On repeated abdominal CT pancreas changes were suggestive of fulminant pancreatitis. Patient did not respond to treatment and passed away 48 hours after admission.

Hypertriglyceridemia complications can be mild or fatal as in these cases. They were evaluated by a primary care physician before complications occur and had secondary causes that predispose them to hypertriglyceridemia, but they were not addressed, reason for which these scenarios raise concern of how much we know? How much we are doing to prevent these outcomes?... Awareness of hypertriglyceridemia management and adverse effects is necessary to avoid complications and fatal outcomes. Is time!

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<![CDATA[SAT-LB92 Sex Hormones Therapy Differentially Modulates HDL Function in Transgender Individuals]]> https://www.researchpad.co/article/elastic_article_8791 Background/aim: The main proposed atheroprotective function of high-density lipoproteins (HDL) lays on their role to promote macrophage cholesterol efflux. An insightful way to learn more about the effects of sex hormones on HDL function is to study changes during hormone therapy. The present study was aimed at evaluating the effects of exogenous sex hormones administration on HDL cholesterol efflux capacity (CEC) within transgender individuals. CEC estimates the ability of HDL to remove cholesterol from cells, i.e. the initial step in reverse cholesterol transport.

Subjects/Methods: Transmen were treated with testosterone gel, a mix of testosterone esters once every three weeks) or testosterone undecanoate once every twelve weeks, whereas transwomen were treated with either oral estradiol valerate or a transdermal application of estradiol (patches). Cyproterone acetate was prescribed as a testosterone-blocking agent to all transwomen. HDL function was evaluated by a radioisotopic technique. Hormone levels, lipids and HDL function were evaluated after one year of follow-up.

Results: In transmen (n= 15), testosterone markedly increased (+ 97%; p < 0.0001), whereas luteinizing hormone (LH) decreased significantly (- 64%; p = 0.049). Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were not affected by testosterone treatment, whilst triglycerides (TG) were raised (+ 11.76%; p = 0.0078) and HDL-C reduced (- 19.6%, p=0.0103). Concerning HDL CEC, only the aqueous diffusion process was lowered (- 9.8%; p = 0.0032), an effect directly correlated with HDL-C changes (r = 0.6242, p = 0.0002). Total-, ATP-binding cassette transporter (ABCA1)-, and ABCG1-mediated CEC were not affected by testosterone treatment. In transwomen (n= 15), estradiol levels were raised (+200%, p=0.013) whereas LH and testosterone significantly reduced, i.e. - 97% for both. Relative to lipids, estradiol supplementation reduced total cholesterol (- 10.7%, p=0.0017), HDL-C (- 14.3%, p = 0.0024) and LDL-C (- 10.9%, p = 0.0058). Total HDL CEC decreased (- 11%, p=0.0001) with a specific decrement in CEC mediated by the ATP-binding cassette transporter (ABCA1) (-24%, p = 0.0003) and aqueous diffusion (-4.7%, p = 0.0014). This last was associated to a reduction in HDL-C (r = 0.4084, p = 0.0251). Conversely, the drop in ABCA1 and total CEC did not associate to reductions in HDL-C levels.

Conclusions: In transmen, testosterone supplementation was associated with a reduction in aqueous diffusion-mediated CEC, an effect potentially dependent to HDL-C changes. In transwomen, estrogen significantly decreased HDL function (CEC), independent of HDL-C levels changes.

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<![CDATA[SAT-573 Eruptive Xanthomas in a Patient with Hypertriglyceredemia and Type 2 Diabetes Mellitus]]> https://www.researchpad.co/article/elastic_article_8647 BACKGROUND: Eruptive xanthomas are rare, asymptomatic, cutaneous lesions and are markers for serious underlying metabolic disorders that demand an early diagnosis to prevent morbidity and mortality.

Clinical Case: A 27 years old obese female presented with generalized, pruritic eruptions. The eruptions had been present for approximately three weeks. Crops of firm yellow-red circumscribed Papules (diameter 1–3 mm) distributed on the extensor surfaces of both the upper and the lower extremities which were few in numbers to begin with but increased in density subsequently spreading to involve her back, abdomen, knees, and posterior thighs. The patient besides being obese had no other significant past medical or family history. Labs: FBS:258 mg/dl (80-100mg/dl), HbA1c:11.7%(<5.6%), Total lipids: 3680 mg/dl (400–1000 mg/dl), Total Cholesterol: 857 mg/dl (120–200 mg/dl), Triglycerides: 5428 mg/dl (70–150 mg/dl), HDL:15mg/dl (45–64 mg/dl), LDL: 371 mg/l(<130 mg/dl),VLDL: 402 mg/dl (<30 md/dl). Results of kidney, liver and thyroid function tests were normal, as well as amylase and lipase. X-ray chest and abdominal ultrasound were unremarkable. Biopsy of the papules was not carried out due to non-affordability on the part of the patient. The patient was managed by an interdisciplinary approach for diabetes mellitus type 2 and hyperlipidaemia. Treatment was started with oral hypoglycaemic along with lipid lowering agents and the required lifestyle modifications including weight control, adopting a low-fat diet, and regular exercise were advised. The papules resolved within six weeks of the treatment and lab reports indicated improvement in her glycemic control and hypertriglyceridemia. It was clinically diagnosed as Eruptive Xanthomas of secondary hypertriglyceridemia due to diabetes mellitus.

CONCLUSION:

Recognizing eruptive xanthomas and being aware of its association with hypertriglyceridemia and diabetes mellitus can help to decrease any lag between a patient being seen by a physician and treatment for a serious medical conditions such as coronary artery disease and pancreatitis.

REFRENCES: Digby M; Belli R; McGraw T; Lee A (2011). “Eruptive xanthomas as a cutaneous manifestation of hypertriglyceridemia: a case report”. J Clin Aesthet Dermatol. 4: 44–6. PMC 3030216Freely accessible. PMID 21278899.

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<![CDATA[SAT-577 Severe Asymptomatic Hypertriglyceridemia]]> https://www.researchpad.co/article/elastic_article_8609 Background

Case reports of patients with severely elevated serum triglyceride levels (>1000 mg/dL) have been documented where Insulin infusions, heparin and plasmapheresis have demonstrated rapid and successful decrease in serum Triglyceride levels. The benefits of one approach versus the other to prevent major complications such as cardiovascular events or acute pancreatitis has not been well investigated. We present the case of a patient with severely elevated serum triglyceride levels without any manifestations.

Case Description

A 53-year-old male presented from his primary care provider’s office due to elevated Triglycerides levels over 6000 as per outpatient lab work. Inpatient labs were unattainable initially due to hemolysis secondary to the severely high lipid content. Patient was admitted to the medical ICU for closer monitoring and initiated on an insulin drip. Two days after insulin initiation patient’s triglyceride levels returned as 2,887 with a total cholesterol count of 848. His insulin drip was continued until his TAG levels were less than 1000. Upon discharge his levels were less than 600.

Discussion

Most patients with hypertriglyceridemia are asymptomatic. However, in patients with levels above 1000 mg/dL, the risk of pancreatitis or cardiovascular event is of concern. Hypertriglyceridemia may account for 1 to 14 percent of cases of acute pancreatitis. Treatment is largely based upon symptoms and complications. In the event of pancreatitis or other cardiovascular complication, plasmapheresis is usually recommended. If asymptomatic, Insulin may be used. Insulin promotes synthesis of lipoprotein lipase which functions to hydrolyze triglycerides, and has been shown to be an effective lowering agent in the treatment of such individuals. Case reports of Heparin being used as a lipid lowering agent have also been documented, but was not used in our particular patient.

Normal triglyceride plasma levels are defined as less than 150 mg/dL. Mild hypertriglyceridemia typically ranges between 150-499 mg/dL, moderate between 500-866 mg/dL, and severe is defined as levels greater than 886 mg/dL. Plasma triglyceride levels above 1000 mg/dL occur in fewer than 1 in 5000 individuals. It is said that patients with TAG levels above 2000 mg/dL almost always have both a secondary and a genetic form of Hypertriglyceridemia. For this reason it is very important to identify these patients as early as possible to treat appropriately. Our patient was a known alcohol abuser, yet without the presence of some polygenic familial disorder, the likelihood of our patient having TAG levels >6000 mg/dL, is very unlikely.

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<![CDATA[SAT-578 A Rare Case of Laboratory Hypertriglyceridemia: Glycerol Kinase Deficiency]]> https://www.researchpad.co/article/elastic_article_7175 Background: Hypertriglyceridemia (HTG) is common; however, pseudo-HTG due to high glycerol in glycerol kinase deficiency (GKD, MIM: 307030) is a rare cause of HTG that need to be delineated for appropriate management. GKD is an X-linked recessive disorder characterized by hyperglycerolemia and glyceroluria. Two of three GKD subtypes are known as “isolate” GKD due to a mutation in GK gene alone: (1) symptomatic juvenile form, and (2) benign adult form, associated with an incidental finding of HTG.

Since most commercial laboratories determine triglyceride (TG) levels by a glycerol measurement, TG-backbone, patients with GKD are mistakenly labelled as having HTG. Glycerol-blanking is required to reveal the actual TG, but it is costly. Since usual TG-lowering medications are ineffective or even harmful, novel methods to screen for individuals with GKD or pseudo-HTG are necessary.

Objective: Through identification of a clinical case of GKD that was diagnosed by glycerol-blanking, we are proposing two potential methods to screen for pseudo-HTG, and presenting their reliability.

Methods: The patient was recruited into an IRB-approved study investigating etiologies of dyslipidemia at the University of Pennsylvania. Patient provided consent for medical record review.

Results: A 49-year-old man was referred for HTG management. His reported TG levels ranged between 490 and 559 mg/dL without any other adverse lipid levels for several years without a history of pancreatitis or diabetes mellitus. Intriguingly, he reported a family history of HTG.

Since TG-lowering medications (fibrates and fish oil) had not reduced his TG levels, specialized lipid analyses were obtained: a non-blanked TG level of 521 mg/dL and a glycerol-blanked TG of 66 mg/dL, consistent with pseudo-HTG or hyperglycerolemia. Repeat glycerol blanked TG levels were 68 and 69 mg/dL, confirming the previous result, and the likely diagnosis of GKD.

With two methods, estimated TG levels were calculated, using some of his laboratory values: (1) modified Friedewald equation to solve for TG with a direct LDL (dLDL) value, and (2) the application of a newly developed formula derived from a collection of 17,545 patient samples, to calculate the absolute TG-gap, using apolipoprotein A and B, estimating TG levels (% deltaTG), and determining whether a TG mesurement might be falsely deviated from the “plausible” TG value.

Although neither methods showed perfect concordance, the calculated TG-valued derived by the two methods were significantly lower than the non-glycerol blanked TG values. The difference was statistically significant (p<0.05).

Conclusion: The patient was clinically diagnosed with GKD, and was taken off of fibrate and the recently added niacin. These two methods can be used quickly to screen for pseudo-HTG or patients with GKD. Currently, it is unknown whether high glycerol levels are associated with high cardiovascular risks.

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<![CDATA[SAT-574 Whole Exome Sequencing Identifies Several Variants Associated with Immune Deficiency, Inflammasomopathy and Non-Ischemic Dilated Cardiomyopathy in a Complex Case of Acquired Generalized Lipodystrophy]]> https://www.researchpad.co/article/elastic_article_6931 Background: Acquired generalized lipodystrophy (AGL) is characterized by near-total fat loss that develops after birth. Although the molecular pathogenesis of AGL is unclear, there is a link to autoimmunity and inflammation. Notably, the panniculitis associated variety of AGL may present with subcutaneous inflammatory nodules that ultimately progress to generalized fat loss. Here, we report on a complex patient with AGL in whom whole-exome sequencing (WES) identified several pathogenic variants and variants of uncertain significance (VUS) that encourage us to think about AGL more broadly. Clinical Case: This is a 38-year-old male who was first diagnosed with juvenile rheumatoid arthritis at age 2, after being evaluated for delayed ability to ambulate. At that time, he was also diagnosed with Weber-Christian disease following a skin biopsy due to the suspicion of panniculitis. Over time, he progressively lost body fat throughout the body and developed hypertriglyceridemia, hypertension, and nephropathy leading to the diagnosis of AGL. At age 10, he was diagnosed with type 1 diabetes mellitus, and at age 14, with autoimmune hepatitis. Due to the tightening of his hands, calf pain, and increased CPK levels, a muscle biopsy was performed, suggesting polymyositis. He had been treated with azathioprine and steroids, which were discontinued at age 26, after a liver biopsy that showed grade 2 fibrosis. Further, he was diagnosed with non-ischemic dilated cardiomyopathy (DCM), evolving with atrial fibrillation with a rapid ventricular response and complicated with left atrial appendage thrombus. Of interest, his mother and two maternal aunts had been diagnosed with atrial fibrillation. One of his maternal uncles presented non-ischemic cardiomyopathy and an early sudden cardiac arrest. His mother also had mitochondrial myopathy, and his father had type 2 diabetes mellitus and IgG deficiency. WES identified three different variants: a maternally inherited pathogenic variant in TTN (c.88473_88477delAGCTT; p.W29493X) associated with DCM, a paternally inherited pathogenic variant in TNFRSF13B (c.310T>C; p.C104R) associated with CVID/IgA deficiency, and a maternally inherited variant of uncertain clinical significance in NLRP3 (c.1469G>A; p.R490K). Although the frequency of this variant was relatively high, several variants in the NLRP3 gene have been previously associated with inflammasomopathy. Conclusion: This case highlights challenging presentations of AGL and the complexity of the disease. As we are yet beginning to understand the molecular mechanisms behind the so-called “acquired fat loss” and its relation to inflammatory and complex immune system diseases, further efforts are critical to better recognize different AGL phenotypes and phenotype-genotype correlations. Additional efforts should be placed on WES for AGL patients and functional validation of identified VUSs.

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<![CDATA[SUN-542 The Effect of Energy Deprivation on Metabolic Hormone Responses to Meals]]> https://www.researchpad.co/article/elastic_article_6797 Background: Intermittent caloric restriction (ICR) has recently gained popularity as a weight-loss strategy; however, fasting metabolic hormones and dynamic meal-related responses, are not well-established in this setting. Methods: We measured metabolic hormone responses to 5-days of neutral or decreased energy availability (NEA, 45 kcal/kg LBM*d vs DEA, 20 kcal/kg LBM*d) in the early follicular phase (EFP) in 19 regularly-cycling, sedentary, women (age 23.36± 2.08 yr; mean±SD). Hunger was assessed using a visual analogue scale on the 5th day of each condition. Scheduled breakfast and lunch were administered according to assigned caloric intake, while an afternoon snack based on NEA was provided on both occasions. Blood was sampled for leptin, insulin, glucose, and GH at 10-min intervals and cortisol was measured at 30-min intervals over eight hours starting at 0800 h, while Orexin A and adiponectin were measured in fasting samples. AUC for each hormone for every meal and diet condition were analyzed using linear mixed models. Insulin and insulin/glucose ratio (I/G) were also adjusted for meal calories. Percentage body fat mass was measured every visit using air displacement plethysmography (BodPod®). Results are presented as least square mean ± sem. Results: There were no differences in body mass index or % fat mass after NEA vs DEA although there was a significant increase in hunger with DEA (p=0.002). Fasting levels of glucose and insulin were unchanged while leptin decreased with DEA (1.27±0.07 and 1.04±0.07 ng/mL, NEA and DEA respectively; p<0.0001), and Orexin A increased (0.55±0.04 and 0.60±0.04 ng/mL; p=0.04). The AUC for glucose was lower with DEA across all meals (p<0.0001). Insulin, I/G and I/G normalized for ingested calories (nI/G) decreased in response to DEA (p<0.005, p<0.05 and p<0.0001). The slope of the increase in leptin across the day was not different between NEA and DEA (p=0.20). Adiponectin, GH and cortisol were unaffected by DEA. Conclusion: These studies indicate that although fasting glucose and insulin are unaffected by short-term caloric restriction, the insulin response to glucose is attenuated even when adjusting for meal-related calories. Orexin A increased and leptin decreased with reduced caloric intake, acting, at least in part, to stimulate appetite. Taken together, these hormonal responses, directed at preserving energy homeostasis, have important implications for understanding the potential efficacy of intermittent caloric restriction.

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<![CDATA[SUN-543 Real World Evidence of Successful Weight Management for the Obese Population: Complete Reversal of Obesity Related Metabolic Co-Morbidities and Weight Loss in Patients Attending a Multidisciplinary Weight Management Clinic in Australia]]> https://www.researchpad.co/article/elastic_article_6724 Over 2.5 billion people worldwide are overweight or obese. Multidisciplinary weight management interventions have evolved to address the complexity of weight loss for those with one or more chronic diseases, and the trend of weight regain. The aim of these interventions is to encourage sustainable lifestyle changes, resulting in weight loss and weight maintenance and improvements in comorbidities. While some prospective clinical trials have demonstrated efficacy, results are often not reported by real life practices.

The aim of this study was to evaluate the effectiveness of a Sydney based multidisciplinary weight management clinic with endocrinology, dietetics, exercise physiology, psychology, and bariatric surgical domains. All patients who attended the clinic for weight loss purposes between March 2017 and April 2019 were included (n=220). A retrospective chart review was conducted. Patient data on weight, BMI, waist circumference, body composition measurements, and selected blood test results and co-morbidities were analysed. All patient therapy included endocrinological input for co-morbidity identification and management, lifestyle intervention (dietetic and exercise physiology input) with optional adjunct pharmacotherapy or psychological counselling. Of the 220 cohort, 20 of the patients had sleeve gastrectomy.

Patient retention in the clinic after the first consultation was 85% (n=186), a high rate within the weight management community. 59% of patients achieved a minimum of 5% total body weight loss, including 18% who achieved greater than 10% total body weight loss. Additionally, 31% of patients lost enough weight to decrease their BMI class by up to 2 or more classes. Of the gastric sleeve cohort average excess body weight loss was 32kg (21-56kg) enhanced by multidisciplinary care in the lead up to surgery. Across the cohort some patients completely reversed co-morbidities; including dyslipidaemia (n=1), hypertension (n=3), NAFLD (n=1), pre-diabetes (n=8) and type 2 diabetes (n=3), OSA (n=1). These results demonstrate that obesity is a chronic condition that can be successfully managed. We have demonstrated significant durable weight loss and improvement in metabolic co-morbidities with holistic coordinated care. Future directions include translating this model of care into standard practice in Australia and other countries where obesity to date not received the same coordinated approach as other chronic conditions.

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<![CDATA[SAT-565 Familial Homozygous Lipoprotein Lipase Defect Presenting with Recurrent Chylomicronemia Syndrome: Making a Case for Elective Plasmapheresis as an Adjuvant Treatment Modality]]> https://www.researchpad.co/article/elastic_article_6019 Background

The chylomicronemia syndrome is a disorder characterized by severe hypertriglyceridemia and fasting chylomicronemia. Type Ia hyperlipoproteinemia is an extremely rare genetic disorder that results from homozygous deficiency in LPL activity. It is characterized by eruptive xanthomas, lipemia retinalis, memory disturbances, hepatosplenomegaly and frequent episodes of pancreatitis. Pharmacologic agents including fibrates, fish oils and statins have been used for treatment. Patients who fail pharmacologic therapy are usually treated with plasmapheresis. This case showed a patient in which joint decision making led to elective plasmapheresis to avoid chylomicronemia syndrome as an adjunct to medical therapy.

Clinical case

A 35-year-old lady without known medical co-morbidity presented with 2 weeks of dull abdominal pain radiating to the back. She developed nausea and vomiting which led to her presentation. There was no history of alcohol use, gall stones, diabetes mellitus or thyroid dysfunction. She was not on any medications. Physical examination was significant for BMI of 18, moderate abdominal tenderness, splenomegaly and an indurated rash in her legs. Laboratory investigation showed elevated lipase and triglyceride level of 3313 (normal 30-50) mg/dL. CT of the abdomen was consistent with acute interstitial pancreatitis. She was managed with insulin drip and fenofibrate and discharged 3 days later on fenofibrate, atorvastatin and long acting insulin. She developed another episode of acute pancreatitis while on medical therapy requiring readmission and initiation of insulin drip 2 months later. However, triglycerides trended upwards when the drip was stopped and symptoms of acute pancreatitis worsened. She subsequently underwent plasmapheresis which led to resolution of symptoms. Despite maximally tolerated pharmacologic therapy, she persistently has triglycerides above 4000s and persistent abdominal discomfort. Genetic testing confirmed homozygous defect in LPL gene. Following an outpatient Endocrinology visit, a decision was made to pursue elective plasmapheresis as an adjunct to therapy. She had on average 2 sessions monthly for 3 months with overall improvement in abdominal discomfort as well as significant improvement in triglyceride levels.

Conclusion

Familial chylomicronemia syndromes often require multimodal therapeutic approaches to prevent morbidity and complications. These include diet and pharmacologic therapy. Although plasmapheresis is often used during hospitalizations for hypertriglyceridemia induced pancreatitis refractory to diet and pharmacologic therapy, it was used in our patient electively and efficaciously to control hypertriglyceridemia and improve symptoms of chylomicronemia syndrome.

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<![CDATA[Significant cardiac disease complicating Graves’ disease in previously healthy young adults]]> https://www.researchpad.co/article/N799f442a-dba1-4542-ab7b-3253ae1ef914

Summary

Graves’ disease is associated with tachydysrythmia, cardiac ischaemia and cardiomyopathy – all uncommon in young adults without previous cardiac disease. We present three young individuals who developed cardiac complications after periods of uncontrolled Graves’ disease. Subject 1: A 34-year-old female had severe thyrotoxic symptoms for weeks. Investigations showed fT4: 98.4 (11–25 pmol/L), fT3: 46.9 (3.1–6.8 pmol/L), TSH <0.01 (0.27–4.2 mU/L) and thyrotrophin receptor antibody (TRAb): 34.8 (<0.9 U//l). She had appropriate treatment but several weeks later she became breathless despite improving thyroid function. Echocardiography showed a pericardial effusion of 2.9 cm. She responded well to steroids and NSAIDs but developed active severe Graves’ orbitopathy after early total thyroidectomy. Subject 2: A 28-year-old male developed thyrotoxic symptoms (fT4: 38 pmol/L, fT3: 13.9 pmol/L, TSH <0.01 (for over 6 months) and TRAb: 9.3 U/L). One month after starting carbimazole, he developed acute heart failure (HF) due to severe dilated cardiomyopathy – EF 10–15%. He partially recovered after treatment – EF 28% and had early radioiodine treatment. Subject 3: A 42-year-old woman who had been thyrotoxic for several months (fT4: 54.3; fT3 >46.1; TSH <0.01; TRAb: 4.5) developed atrial fibrillation (AF) and heart failure. Echocardiography showed cardiomegaly – EF 29%. She maintains sinus rhythm following early total thyroidectomy (EF 50%). Significant cardiac complications may occur in previously fit young adults, who have had uncontrolled Graves’ disease for weeks to months. Cardiac function recovers in the majority, but early definitive treatment should be discussed to avoid Graves’ disease relapse and further cardiac decompensation.

Learning points:

  • Cardiac complications of Graves’ disease are uncommon in young adults without previous cardiac disease.

  • These complications may however occur if Graves’ disease had been poorly controlled for several weeks or months prior to presentation.

  • Persistent symptoms after adequate control should alert clinicians to the possibility of cardiac disease.

  • Specific treatment of Graves’ disease and appropriate cardiac intervention results in complete recovery in the majority and carries a good prognosis.

  • Early definitive treatment should be offered to them to prevent cardiac decompensation at times of further relapse.

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<![CDATA[The effect of a programme to improve men’s sedentary time and physical activity: The European Fans in Training (EuroFIT) randomised controlled trial]]> https://www.researchpad.co/article/5c63396fd5eed0c484ae6703

Background

Reducing sitting time as well as increasing physical activity in inactive people is beneficial for their health. This paper investigates the effectiveness of the European Fans in Training (EuroFIT) programme to improve physical activity and sedentary time in male football fans, delivered through the professional football setting.

Methods and findings

A total of 1,113 men aged 30–65 with self-reported body mass index (BMI) ≥27 kg/m2 took part in a randomised controlled trial in 15 professional football clubs in England, the Netherlands, Norway, and Portugal. Recruitment was between September 19, 2015, and February 2, 2016. Participants consented to study procedures and provided usable activity monitor baseline data. They were randomised, stratified by club, to either the EuroFIT intervention or a 12-month waiting list comparison group. Follow-up measurement was post-programme and 12 months after baseline. EuroFIT is a 12-week, group-based programme delivered by coaches in football club stadia in 12 weekly 90-minute sessions. Weekly sessions aimed to improve physical activity, sedentary time, and diet and maintain changes long term. A pocket-worn device (SitFIT) allowed self-monitoring of sedentary time and daily steps, and a game-based app (MatchFIT) encouraged between-session social support. Primary outcome (objectively measured sedentary time and physical activity) measurements were obtained for 83% and 85% of intervention and comparison participants. Intention-to-treat analyses showed a baseline-adjusted mean difference in sedentary time at 12 months of −1.6 minutes/day (97.5% confidence interval [CI], −14.3–11.0; p = 0.77) and in step counts of 678 steps/day (97.5% CI, 309–1.048; p < 0.001) in favor of the intervention. There were significant improvements in diet, weight, well-being, self-esteem, vitality, and biomarkers of cardiometabolic health in favor of the intervention group, but not in quality of life. There was a 0.95 probability of EuroFIT being cost-effective compared with the comparison group if society is willing to pay £1.50 per extra step/day, a maximum probability of 0.61 if society is willing to pay £1,800 per minute less sedentary time/day, and 0.13 probability if society is willing to pay £30,000 per quality-adjusted life-year (QALY). It was not possible to blind participants to group allocation. Men attracted to the programme already had quite high levels of physical activity at baseline (8,372 steps/day), which may have limited room for improvement. Although participants came from across the socioeconomic spectrum, a majority were well educated and in paid work. There was an increase in recent injuries and in upper and lower joint pain scores post-programme. In addition, although the five-level EuroQoL questionnaire (EQ-5D-5L) is now the preferred measure for cost-effectiveness analyses across Europe, baseline scores were high (0.93), suggesting a ceiling effect for QALYs.

Conclusion

Participation in EuroFIT led to improvements in physical activity, diet, body weight, and biomarkers of cardiometabolic health, but not in sedentary time at 12 months. Within-trial analysis suggests it is not cost-effective in the short term for QALYs due to a ceiling effect in quality of life. Nevertheless, decision-makers may consider the incremental cost for increase in steps worth the investment.

Trial registration

International Standard Randomised Controlled Trials, ISRCTN-81935608.

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<![CDATA[Influence of long term administration of tofogliflozin on chronic inflammation of visceral adipose tissue in mice with obesity induced by a high-fat diet]]> https://www.researchpad.co/article/5c57e6c6d5eed0c484ef3d61

We previously found that senescence of cluster of differentiation 4 (CD4) T cells is accelerated in the visceral adipose tissue (VAT) of mice with diet-induced obesity (DIO) due to a high-fat diet (HFD), and that these senescent-associated T cells cause chronic inflammation of visceral adipose tissue through secretion of osteopontin, provoking systemic insulin resistance. In this study, we examined whether the development of chronic inflammation and senescence-associated T cells in VAT of DIO mice was improved by long-term weight loss after switching to normal chow (NC) or by administration of a sodium glucose cotransporter 2 inhibitor (tofogliflozin). Wild-type mice were fed an HFD for 26 weeks from 4 weeks old. At 30 weeks of age, half of these DIO mice were switched to NC with or without 0.005% tofogliflozin for 38 weeks. The other mice remained on the HFD with or without 0.005% tofogliflozin for 38 weeks. When DIO mice were switched to NC, their weight decreased to that of mice kept on NC since weaning. After 38 weeks (68 weeks of age), chronic inflammation of the VAT subsided with disappearance of senescence-associated T cells. In the HFD groups, the carbohydrate intake per mouse was half or less of that in the NC group, and urinary glucose excretion by the effect of tofogliflozin was lower in the HFD mice than in the NC mice. Mice that remained on the HFD showed no improvement in chronic inflammation in VAT, possibly because urinary glucose excretion was not sufficiently promoted by tofogliflozin due to the low carbohydrate intake. Thus, no improvement in glucose metabolism or weight loss was observed in these mice.

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<![CDATA[Maintenance of body weight is an important determinant for the risk of ischemic stroke: A nationwide population-based cohort study]]> https://www.researchpad.co/article/5c37b7acd5eed0c4844908b8

Background

Overweight is known as a risk factor for ischemic stroke. However, the effect of weight change on the development of ischemic stroke remains controversial. We investigated the relationship between weight change and the risk of ischemic stroke using a nationwide population-based cohort.

Methods

Our study enrolled 11,084,683 participants (Mean age 49.7±13.5 years, range 20–114 years) in the Korean National Health Screening Program from 2009 to 2012. Weight change was calculated using the difference between the baseline weight and the weight at health screening four years prior to the baseline. The occurrence of newly-diagnosed ischemic stroke was observed until the end of 2015. We categorized the study population according to weight change and performed multivariable analysis to compare the risk.

Results

Ischemic stroke was newly diagnosed in 113,591 subjects. The crude incidence rates of ischemic stroke per 1000 person-years according to the change in body weight were 3.059, 1.906, and 1.491 in the <-5%, ±5%, and ≥+5% groups, respectively. After adjusting all variables, the hazard ratio (HR) of ischemic stroke was higher in subjects who underwent weight loss (HR 1.152) or weight gain (HR 1.087) than in those who maintained their weight. When analyzed by eight groups of 5% intervals, the risk showed a U-shaped curve with those who maintained their weight showing the lowest risk.

Conclusions

The risk of ischemic stroke was gradually increased in those who lost or gained more than 5% of their weight over four years, after adjusting for confounders. We should be aware of the increased risk of ischemic stroke in people who undergo weight change and should identify and manage the cause of weight change.

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<![CDATA[Weight cycling and cardiovascular outcome in women with suspected ischemia: A report from the NHLBI-sponsored WISE Study]]> https://www.researchpad.co/article/5c0ed770d5eed0c484f14134

Background

We previously reported in a cross-sectional analysis an adverse relationship between weight cycling and HDL-cholesterol but not angiographic obstructive coronary artery disease (CAD) among women undergoing coronary angiography for suspected ischemia in the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE). We now examine the relationship between weight cycling and prospective adverse cardiovascular outcome in this group.

Methods

795 women enrolled between 1996–2001 in the WISE undergoing coronary angiography for evaluation of suspected ischemia and followed for a median of 6.0 years (interquartile range = 3.4 years). Adverse outcome was defined as a composite of all-cause death, cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure. Weight cycling was defined as the intentional loss of at least 10 lbs. (4.5 kgs.) at least three times during the women’s lifetime.

Results

Women (n = 224) who reported a history of weight cycling were younger; more often white and better educated compared those without this history. At baseline, women with a weight cycling history had lower HDL-C values, higher body mass index, larger waist circumferences and higher values for fasting blood sugar, but no difference in obstructive CAD prevalence or severity. There was an inverse relationship between weight cycling and adverse composite cardiovascular outcome, whereby fewer of women with a history of weight cycling experienced an adverse outcome as compared to non-cyclers (21% vs 29%, respectively, p = 0.03).

Conclusions

Despite an adverse association with HDL-cholesterol in women undergoing coronary angiography for suspected ischemia, weight cycling was associated with a lower adverse outcome rate in women with suspected ischemia.

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<![CDATA[At similar weight loss, dietary composition determines the degree of glycemic improvement in diet-induced obese C57BL/6 mice]]> https://www.researchpad.co/article/5b603630463d7e4090b7ce1f

Background

Achieving weight loss is the cornerstone of the treatment of the metabolic consequences of obesity, in particular of glucose intolerance.

Objective

To determine whether improvement in glucose control depends on dietary macronutrient composition of the diet at identical weight loss.

Materials and methods

Twenty-two weeks old diet-induced obese C57BL/6 mice lost weight through caloric restriction on normal chow (R-NC) or high fat diet (R-HF). Control mice were fed normal chow (LEAN) or high fat diet (OBESE) ad libitum. Body weight and composition were assessed after 8 weeks of dietary intervention. Glucose homeostasis was evaluated by intraperitoneal glucose tolerance tests (IPGTT). Epididymal white adipose (eWAT) and hepatic tissues were analyzed by immunohistochemistry and RT-qPCR.

Results

By 30 weeks of age, the body weight of the mice on R-NC (31.6±1.7g, mean±SEM) and R-HF (32.3±0.9g) was similar to LEAN mice (31.9±1.4g), while OBESE mice weighed 51.7±2.4g. Glucose tolerance in R-NC was better than in LEAN mice (69% AUC IPGTT, P 0.0168) whereas R-HF mice remained significantly less glucose tolerant (125% AUC IPGTT, P 0.0279 vs LEAN), despite identical weight loss. The eWAT pads and adipocyte size were similar in LEAN and R-NC mice, while the eWAT pad size of R-HF was 180% of R-NC (P < 0.0001) and the average adipocyte size of R-HF mice was 134% of R-NC fed mice (P 0.0285). No LEAN or R-NC mice had hepatic steatosis, in contrast to 28.6% of R-HF mice. Compared to OBESE mice, inflammatory markers were lower in eWAT and liver tissue of R-NC, but not in R-HF mice. Measures of visceral adiposity correlated well with glucose tolerance parameters.

Conclusions

In mice, caloric restriction on a normal chow diet improved glucose tolerance significantly more when identical weight loss was achieved on a high fat diet.

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<![CDATA[SAT-575 Association Between Baseline Fitness and Changes in Physical Activity and Weight Loss in an 18-Month Behavioral Weight Loss Program]]> https://www.researchpad.co/article/N41389e1c-0abe-469b-b94e-cf54331a415e <![CDATA[SUN-545 High Prevalence of Cardiometabolic Diseases and Abdominal Aortic Calcification in Psoriasis]]> https://www.researchpad.co/article/N8f234d4e-6a25-4dc0-9df4-13c7a427d0a9 <![CDATA[SAT-571 Rare Case of Tocilizumab-Induced Severe Hypertriglyceridemia]]> https://www.researchpad.co/article/N3242dd88-cbda-41c2-8ec9-b5ec5e53f157 <![CDATA[SAT-569 Management of Severe Gestational Hypertriglyceridemia]]> https://www.researchpad.co/article/N8c58332d-f811-4493-b8a3-47c020d1c982 900 mg/dL and gemfibrozil therapy was advised, however reported nonadherence. In current pregnancy and after counseling, she was prescribed omega-3 acid ethyl esters (Lovaza) 2 grams twice a day and referred to maternal fetal medicine. Triglyceride level on admission was 3640 mg/dL, and she admitted to poor adherence to Lovaza. Liver function tests were within normal limits. She was started on an insulin drip, as well omega-3 fatty acids 4g daily. However, the triglyceride level remained elevated despite 72 hours on the insulin drip and it was subsequently discontinued. Plasmapheresis was discussed but deferred given no evidence of pancreatitis. Gemfibrozil 600mg twice a day was added to the omega-3 fatty acids which were titrated up to 2g three times a day. On her day of discharge, her triglyceride level was 2200 mg/dL and abdominal pain had resolved. She was maintained on gemfibrozil and Omega-3 fatty acids, with plans to increase them by 1g per week to reach a goal of 10g per day with a goal triglyceride level <1000mg/dL. Pre-gestational diabetes was tightly controlled with insulin. She was also seen by the nutritionist for counseling of a low fat diet and was followed very closely as an outpatient. Although the omega-3 fatty acids were titrated to 8g per day, the triglyceride level remained ~2000mg/dL. She remained asymptomatic and delivered a healthy baby boy weighing 3446 grams at 36 weeks 4 days, with no complications. She continues follow up with endocrinology with triglycerides 6 months later being 1618 mg/dl.Conclusion: We present a patient with severe gestational hypertriglyceridemia with a known history of pancreatitis. Due to the rarity of this condition, there is limited data on the safety of treatments for hypertriglyceridemia in pregnant women. This case demonstrates the use of gemfibrizol is appropriate when the hypertriglyceridemia threatens the health of the mother and baby. Further studies are needed to establish efficacy and safety of the use of these treatments in pregnant patients. ]]>