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Novel therapeutic targets and emerging treatments for atherosclerotic cardiovascular disease.
Zheng, WC, Chan, W, Dart, A, Shaw, JA
European heart journal. Cardiovascular pharmacotherapy. 2024;(1):53-67
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality worldwide. Even with excellent control of low-density lipoprotein cholesterol (LDL-C) levels, adverse cardiovascular events remain a significant clinical problem worldwide, including among those without any traditional ASCVD risk factors. It is necessary to identify novel sources of residual risk and to develop targeted strategies that address them. Lipoprotein(a) has become increasingly recognized as a new cardiovascular risk determinant. Large-scale clinical trials have also signalled the potential additive cardiovascular benefits of decreasing triglycerides beyond lowering LDL-C levels. Since CANTOS (Anti-inflammatory Therapy with Canakinumab for Atherosclerotic Disease) demonstrated that antibodies against interleukin-1β may decrease recurrent cardiovascular events in secondary prevention, various anti-inflammatory medications used for rheumatic conditions and new monoclonal antibody therapeutics have undergone rigorous evaluation. These data build towards a paradigm shift in secondary ASCVD prevention, underscoring the value of targeting multiple biological pathways in the management of both lipid levels and systemic inflammation. Evolving knowledge of the immune system, and the gut microbiota may result in opportunities for modifying previously unrecognized sources of residual inflammatory risk. This review provides an overview of novel therapeutic targets for ASCVD and emerging treatments with a focus on mechanisms, efficacy, and safety.
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Association between weight bias internalization and metabolic syndrome among treatment-seeking individuals with obesity.
Pearl, RL, Wadden, TA, Hopkins, CM, Shaw, JA, Hayes, MR, Bakizada, ZM, Alfaris, N, Chao, AM, Pinkasavage, E, Berkowitz, RI, et al
Obesity (Silver Spring, Md.). 2017;25(2):317-322
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Plain language summary
Weight stigma is a psychosocial consequence in which individuals with obesity experience public discrimination and devaluation. Some individuals apply these negative stereotypes to themselves, which creates a self-directed stigma referred to as weight bias internalization (WBI). While studies have found perceived weight discrimination to be associated with an increased risk of mortality, no study has investigated the relationship between WBI and obesity on the risk of developing metabolic syndrome (MetS). The aim of this study is to examine the relationship between WBI and MetS. The authors hypothesised that among obese individuals, higher levels of WBI would be associated with increased odds of having MetS. Among the 178 obese adults recruited, 159 completed the study. Tests included anthropometric measurements, blood analysis, the Weight Bias Internalization Scale (WBIS) and the Patient Health Questionnaire. This study found that individuals who self-stigmatise may have a heightened risk of dyslipidemia, one component of MetS. Based on these results, the authors conclude that weight stigma is a chronic stressor and may contribute to poor health. Future studies are needed to identify specific pathways in which WBI exacerbates cardiometaoblic risk factors.
Abstract
OBJECTIVE Weight stigma is a chronic stressor that may increase cardiometabolic risk. Some individuals with obesity self-stigmatize (i.e., weight bias internalization, WBI). No study to date has examined whether WBI is associated with metabolic syndrome. METHODS Blood pressure, waist circumference, and fasting glucose, triglycerides, and high-density lipoprotein cholesterol were measured at baseline in 178 adults with obesity enrolled in a weight-loss trial. Medication use for hypertension, dyslipidemia, and prediabetes was included in criteria for metabolic syndrome. One hundred fifty-nine participants (88.1% female, 67.3% black, mean BMI = 41.1 kg/m2 ) completed the Weight Bias Internalization Scale and Patient Health Questionnaire (PHQ-9, to assess depressive symptoms). Odds ratios and partial correlations were calculated adjusting for demographics, BMI, and PHQ-9 scores. RESULTS Fifty-one participants (32.1%) met criteria for metabolic syndrome. Odds of meeting criteria for metabolic syndrome were greater among participants with higher WBI, but not when controlling for all covariates (OR = 1.46, 95% CI = 1.00-2.13, P = 0.052). Higher WBI predicted greater odds of having high triglycerides (OR = 1.88, 95% CI = 1.14-3.09, P = 0.043). Analyzed categorically, high (vs. low) WBI predicted greater odds of metabolic syndrome and high triglycerides (Ps < 0.05). CONCLUSIONS Individuals with obesity who self-stigmatize may have heightened cardiometabolic risk. Biological and behavioral pathways linking WBI and metabolic syndrome require further exploration.
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Binge-eating disorder and the outcome of bariatric surgery in a prospective, observational study: Two-year results.
Chao, AM, Wadden, TA, Faulconbridge, LF, Sarwer, DB, Webb, VL, Shaw, JA, Thomas, JG, Hopkins, CM, Bakizada, ZM, Alamuddin, N, et al
Obesity (Silver Spring, Md.). 2016;24(11):2327-2333
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Binge eating disorder is characterised by the consumption of an objectively large amount of food in a discrete period of time (i.e. 2hrs) with an accompanying loss of control over eating. This study is a follow-up study that examined weight loss over an average of 24 months post bariatric surgery (as most studies are based on a shorter duration i.e. less than 12 months) in 59 patients. Another aim of the study was whether bariatric surgery had any effects on the remission or precipitation of binge eating. Results indicate that patients with a preoperative diagnosis of binge-eating disorder lost significantly less weight 2 years after surgery than those individuals who were free from binge-eating prior surgery. However, those with a diagnosis of binge-eating disorder who received lifestyle modifications lost significantly less than those who had bariatric surgery. Authors conclude that bariatric-surgery may be a useful long-term weight loss strategy for patients with eating disorders. However, they also recommend that these patients may benefit from additional counselling and behavioural support, such as cognitive behaviour therapy.
Abstract
OBJECTIVE A previous study reported that preoperative binge-eating disorder (BED) did not attenuate weight loss at 12 months after bariatric surgery. This report extends the authors' prior study by examining weight loss at 24 months. METHODS A modified intention-to-treat population was used to compare 24-month changes in weight among 59 participants treated with bariatric surgery, determined preoperatively to be free of a current eating disorder, with changes in 33 surgically treated participants with BED. Changes were also compared with 49 individuals with obesity and BED who sought lifestyle modification for weight loss. Analyses included all available data points and were adjusted for covariates. RESULTS At month 24, surgically treated patients with BED preoperatively lost 18.6% of initial weight, compared with 23.9% for those without BED (P = 0.049). (Mean losses at month 12 had been 21.5% and 24.2%, respectively; P = 0.23.) Participants with BED who received lifestyle modification lost 5.6% at 24 months, significantly less than both groups of surgically treated patients (P < 0.001). CONCLUSIONS These results suggest that preoperative BED attenuates long-term weight loss after bariatric surgery. We recommend that patients with this condition, as well as other eating disturbances, receive adjunctive behavioral support, the timing of which remains to be determined.
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Mindful decision making and inhibitory control training as complementary means to decrease snack consumption.
Forman, EM, Shaw, JA, Goldstein, SP, Butryn, ML, Martin, LM, Meiran, N, Crosby, RD, Manasse, SM
Appetite. 2016;:176-183
Abstract
OBJECTIVE Obesity is largely attributable to excess caloric intake, in particular from "junk" foods, including salty snack foods. Evidence suggests that neurobiological preferences to consume highly hedonic foods translate (via implicit processes) into poor eating choices, unless overturned by inhibitory mechanisms or interrupted by explicit processes. The primary aim of the current study was to test the independent and combinatory effects of a computerized inhibitory control training (ICT) and a mindful decision-making training (MDT) designed to facilitate de-automatization. METHODS We randomized 119 habitual salty snack food eaters to one of four short, training conditions: MDT, ICT, both MDT and ICT, or neither (i.e., psychoeducation). For 7 days prior to the intervention and 7 days following the intervention, participants reported on their salty snack food consumption 2 times per day, on 3 portions of their days, using a smartphone-based ecological momentary assessment system. Susceptibility to emotional eating cues was measured at baseline. RESULTS Results indicated that the effect of MDT was consistent across levels of trait emotional eating, whereas the benefit of ICT was apparent only at lower levels of emotional eating. No synergistic effect of MDT and ICT was detected. CONCLUSIONS These results provide qualified support for the efficacy of both types of training for decreasing hedonically-motivated eating. Moderation effects suggest that those who eat snack foods for reasons unconnected to affective experiences (i.e., lower in emotional eating) may derive benefit from a combination of ICT and MDT. Future research should investigate the additive benefit of de-automization training to standard weight loss interventions.
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Can evaluative conditioning decrease soft drink consumption?
Shaw, JA, Forman, EM, Espel, HM, Butryn, ML, Herbert, JD, Lowe, MR, Nederkoorn, C
Appetite. 2016;:60-70
Abstract
The present study examined the effect of a picture-picture evaluative conditioning (EC) procedure on soft drink (soda) outcomes, including negative implicit attitudes, consumption during a taste test, and real-world consumption reported during the week after the intervention. In the EC condition (n = 43), soda images were paired with disgust images and water images were paired with pleasant images, whereas in the control condition (n = 41), the same images were viewed without pairing. The EC condition showed a larger reduction in real-world soda consumption across the week following the intervention. However, individuals in the EC condition did not consume less soda during a taste test immediately following the intervention. EC only significantly increased negative implicit attitudes towards soda among individuals who already had relatively higher baseline negative attitudes. These findings generally favored the potential for EC to impact soda drinking habits, but suggest that a brief EC intervention may not be strong enough to change attitudes towards a well-known brand unless negative attitudes are already present.
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Insulin therapy and dietary adjustments to normalize glycemia and prevent nocturnal hypoglycemia after evening exercise in type 1 diabetes: a randomized controlled trial.
Campbell, MD, Walker, M, Bracken, RM, Turner, D, Stevenson, EJ, Gonzalez, JT, Shaw, JA, West, DJ
BMJ open diabetes research & care. 2015;(1):e000085
Abstract
INTRODUCTION Evening-time exercise is a frequent cause of severe hypoglycemia in type 1 diabetes, fear of which deters participation in regular exercise. Recommendations for normalizing glycemia around exercise consist of prandial adjustments to bolus insulin therapy and food composition, but this carries only short-lasting protection from hypoglycemia. Therefore, this study aimed to examine the impact of a combined basal-bolus insulin dose reduction and carbohydrate feeding strategy on glycemia and metabolic parameters following evening exercise in type 1 diabetes. METHODS Ten male participants (glycated hemoglobin: 52.4±2.2 mmol/mol), treated with multiple daily injections, completed two randomized study-days, whereby administration of total daily basal insulin dose was unchanged (100%), or reduced by 20% (80%). Participants attended the laboratory at ∼08:00 h for a fasted blood sample, before returning in the evening. On arrival (∼17:00 h), participants consumed a carbohydrate meal and administered a 75% reduced rapid-acting insulin dose and 60 min later performed 45 min of treadmill running. At 60 min postexercise, participants consumed a low glycemic index (LGI) meal and administered a 50% reduced rapid-acting insulin dose, before returning home. At ∼23:00 h, participants consumed a LGI bedtime snack and returned to the laboratory the following morning (∼08:00 h) for a fasted blood sample. Venous blood samples were analyzed for glucose, glucoregulatory hormones, non-esterified fatty acids, β-hydroxybutyrate, interleukin 6, and tumor necrosis factor α. Interstitial glucose was monitored for 24 h pre-exercise and postexercise. RESULTS Glycemia was similar until 6 h postexercise, with no hypoglycemic episodes. Beyond 6 h glucose levels fell during 100%, and nine participants experienced nocturnal hypoglycemia. Conversely, all participants during 80% were protected from nocturnal hypoglycemia, and remained protected for 24 h postexercise. All metabolic parameters were similar. CONCLUSIONS Reducing basal insulin dose with reduced prandial bolus insulin and LGI carbohydrate feeding provides protection from hypoglycemia during and for 24 h following evening exercise. This strategy is not associated with hyperglycemia, or adverse metabolic disturbances. CLINICAL TRIALS NUMBER NCT02204839, ClinicalTrials.gov.
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Comparison of appetite responses to high- and low-glycemic index postexercise meals under matched insulinemia and fiber in type 1 diabetes.
Campbell, MD, Gonzalez, JT, Rumbold, PL, Walker, M, Shaw, JA, Stevenson, EJ, West, DJ
The American journal of clinical nutrition. 2015;(3):478-86
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Abstract
BACKGROUND Patients with type 1 diabetes face heightened risk of hypoglycemia after exercise. Subsequent overfeeding, as a preventative measure against hypoglycemia, negates the energy deficit after exercise. Patients are also required to reduce the insulin dose administered with postexercise foods to further combat hypoglycemia. However, the insulin dose is dictated solely by the carbohydrate content, even though postprandial glycemia is vastly influenced by glycemic index (GI). With a need to control the postexercise energy balance, appetite responses after meals differing in GI are of particular interest. OBJECTIVES We assessed the appetite response to low-glycemic index (LGI) and high-glycemic index (HGI) postexercise meals in type 1 diabetes patients. This assessment also offered us the opportunity to evaluate the influence of GI on appetite responses independently of insulinemia, which confounds findings in individuals without diabetes. DESIGN Ten physically active men with type 1 diabetes completed 2 trials in a randomized crossover design. After 45 min of treadmill exercise at 70% of the peak oxygen uptake, participants consumed an LGI (GI ∼37) or HGI (GI ∼92) meal with a matched macronutrient composition, negligible fiber content, and standardized insulin-dose administration. The postprandial appetite response was determined for 180 min postmeal. During this time, circulating glucose, insulin, glucagon, and glucagon-like peptide-1 (GLP-1) concentrations and subjective appetite ratings were determined. RESULTS The HGI meal produced an ∼60% greater postprandial glucose area under the curve (AUC) than did the LGI meal (P = 0.008). Insulin, glucagon, and GLP-1 did not significantly differ between trials (P > 0.05). The fullness AUC was ∼25% greater after the HGI meal than after the LGI meal (P < 0.001), whereas hunger sensations were ∼9% lower after the HGI meal than after the LGI meal (P = 0.001). CONCLUSION Under conditions of matched insulinemia and fiber, an HGI postexercise meal suppresses feelings of hunger and augments postprandial fullness sensations more so than an otherwise equivalent LGI meal in type 1 diabetes patients.
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A low-glycemic index meal and bedtime snack prevents postprandial hyperglycemia and associated rises in inflammatory markers, providing protection from early but not late nocturnal hypoglycemia following evening exercise in type 1 diabetes.
Campbell, MD, Walker, M, Trenell, MI, Stevenson, EJ, Turner, D, Bracken, RM, Shaw, JA, West, DJ
Diabetes care. 2014;(7):1845-53
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Abstract
OBJECTIVE To examine the influence of the glycemic index (GI) of foods consumed after evening exercise on postprandial glycemia, metabolic and inflammatory markers, and nocturnal glycemic control in type 1 diabetes. RESEARCH DESIGN AND METHODS On two evenings (∼1700 h), 10 male patients (27 ± 5 years of age, HbA1c 6.7 ± 0.7% [49.9 ± 8.1 mmol/mol]) were administered a 25% rapid-acting insulin dose with a carbohydrate bolus 60 min before 45 min of treadmill running. At 60 min postexercise, patients were administered a 50% rapid-acting insulin dose with one of two isoenergetic meals (1.0 g carbohdyrate/kg body mass [BM]) matched for macronutrient content but of either low GI (LGI) or high GI (HGI). At 180 min postmeal, the LGI group ingested an LGI snack and the HGI group an HGI snack (0.4 g carbohdyrate/kg BM) before returning home (∼2300 h). Interval samples were analyzed for blood glucose and lactate; plasma glucagon, epinephrine, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α); and serum insulin, cortisol, nonesterified fatty acid, and β-hydroxybutyrate concentrations. Interstitial glucose was recorded for 20 h postlaboratory attendance through continuous glucose monitoring. RESULTS Following the postexercise meal, an HGI snack induced hyperglycemia in all patients (mean ± SD glucose 13.5 ± 3.3 mmol/L) and marked increases in TNF-α and IL-6, whereas relative euglycemia was maintained with an LGI snack (7.7 ± 2.5 mmol/L, P < 0.001) without inflammatory cytokine elevation. Both meal types protected all patients from early hypoglycemia. Overnight glycemia was comparable, with a similar incidence of nocturnal hypoglycemia (n = 5 for both HGI and LGI). CONCLUSIONS Consuming LGI food with a reduced rapid-acting insulin dose following evening exercise prevents postprandial hyperglycemia and inflammation and provides hypoglycemia protection for ∼8 h postexercise; however, the risk of late nocturnal hypoglycemia remains.
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The mind your health project: a randomized controlled trial of an innovative behavioral treatment for obesity.
Forman, EM, Butryn, ML, Juarascio, AS, Bradley, LE, Lowe, MR, Herbert, JD, Shaw, JA
Obesity (Silver Spring, Md.). 2013;(6):1119-26
Abstract
OBJECTIVE To determine whether acceptance-based behavioral treatment (ABT) would result in greater weight loss than standard behavioral treatment (SBT), and whether treatment effects were moderated by interventionist expertise or participants' susceptibility to eating cues. Recent research suggests that poor long-term weight-control outcomes are due to lapses in adherence to weight-control behaviors and that adherence might be improved by enhancing SBT with acceptance-based behavioral strategies. DESIGN AND METHODS Overweight participants (n = 128) were randomly assigned to 40 weeks of SBT or ABT. RESULTS Both groups produced significant weight loss, and when administered by experts, weight loss was significantly higher in ABT than SBT at post-treatment (13.17% vs. 7.54%) and 6-month follow-up (10.98% vs. 4.83%). Moreover, 64% of those receiving ABT from experts (vs. 46% for SBT) maintained at least a 10% weight loss by follow-up. Moderation analyses revealed a powerful advantage, at follow-up, of ABT over SBT in those potentially more susceptible to eating cues. For participants with greater baseline depression symptomology, weight loss at follow-up was 11.18% in ABT versus 4.63% in SBT; other comparisons were 10.51% versus 6.00% (emotional eating), 8.29% versus 6.35% (disinhibition), and 9.70% versus 4.46% (responsivity to food cues). Mediation analyses produced partial support for theorized food-related psychological acceptance as a mechanism of action. CONCLUSIONS Results offer strong support for the incorporation of acceptance-based skills into behavioral weight loss treatments, particularly among those with greater levels of depression, responsivity to the food environment, disinhibition, and emotional eating, and especially when interventions are provided by weight-control experts.
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Chance happenings in life and psychotherapy.
Shaw, JA
Psychiatry. 2009;(1):1-12
Abstract
This paper will focus on chance happenings and man's struggles to make sense of those random events that occur in everyday life. There is a readiness to deny chance happenings as powerful mediators in our life course and to transfer the guidance of the world to divine providence, to anthropomorphize fate, to search for blame, and to create conspiratorial theories out of natural disasters. Emphasis will be placed on understanding chance happenings from an exploration of coincidences, experiences perceived beyond coincidences, scientific predictors of causality, and developmental perspectives, as well as the individual's psychological strategies for coping with a fateful event, an acute traumatic moment in which there is sudden awareness of a perceived threat of injury and to life itself. The role of chance and environmental happenings in psychotherapy will be discussed with clinical vignettes.