Obese Subjects Study Research Articles

Is There a Need for a Dedicated Pharmacokinetic Trial for a Drug in Obese Populations? A Drug Prioritization Decision Tree Framework.

Obesity is a growing global health concern associated with high comorbidity rates, leading to an increasing number of patients who are obese requiring medication. However, clinical trials often exclude or under-represent individuals who are obese, creating the need for a methodology to adjust labeling to ensure safe and effective dosing for all patients. To address this, we developed a 2-part decision tree framework to prioritize drugs for dedicated pharmacokinetic studies in obese subjects. Leveraging current drug knowledge and modeling techniques, the decision tree system predicts expected exposure changes and recommends labeling strategies, allowing stakeholders to prioritize resources toward the drugs most in need. In a case study evaluating 30 drugs from literature across different therapeutic areas, our first decision tree predicted the expected direction of exposure change accurately in 73% of cases. We conclude that this decision tree system offers a valuable tool to advance research in obesity pharmacology and personalize drug development for patients who are obese, ensuring safe and effective medication.

Non-alcohol substance use disorder after bariatric surgery in the prospective, controlled Swedish Obese Subjects study.

The goal of this study was to investigate whether bariatric surgery is associated with substance use disorder (SUD) with substances other than alcohol. The prospective, controlled Swedish Obese Subjects study enrolled 2010 patients with obesity who underwent bariatric surgery (gastric bypass n = 265; vertical banded gastroplasty n = 1369; gastric banding n = 376) and 2037 matched control individuals receiving usual obesity care. Participants with SUD other than alcohol use disorder were identified using International Statistical Classification of Diseases (ICD) codes from the Swedish National Patient Register (covering treatment in hospital but not primary care). Those with a history of non-alcohol SUD were excluded. Median follow-up was 23.8 years. During follow-up, non-alcohol SUD incidence rates per 1000 person-years with 95% CI were 1.6 (0.8-3.1), 0.8 (0.5-1.2), 1.1 (0.5-2.2), and 0.6 (0.4-0.8) for gastric bypass, vertical banded gastroplasty, gastric banding, and control individuals, respectively. Only gastric bypass was associated with increased incidence of non-alcohol SUD (adjusted hazard ratio 2.54 [95% CI: 1.14-5.65], p = 0.022) compared with control participants. Gastric bypass surgery was associated with increased risk of non-alcohol SUD, and this should be considered in long-term postoperative care.

338-OR: Reversal of Insulin Resistance by Resveratrol and Hesperetin Combination in Overweight and Obese Subjects Correlates with Decrease in Expression of Thioredoxin Interacting Protein

Trans-Resveratrol and hesperetin combination (tRES-HESP) in randomized, double-blind, placebo-controlled crossover study in overweight and obese subjects corrected insulin resistance; healthy aging through functional food study (HATFF, Clinicaltrials.gov identifier NCT02095873). tRES-HESP is an optimized supplement for induction of expression of glyoxalase 1 (Glo1) via activation of transcription factor Nrf2. Increased Glo1 expression decreases reactive metabolite, methylglyoxal (MG), contributing to insulin resistance through glycation-linked unfolded protein formation and activation of the unfolded protein response (UPR). Herein, we report further analysis of study variables and follow-up reverse translational studies. With tRES-HESP treatment, plasma MG correlated negatively with peripheral blood mononuclear cell (PBMC) quinone reductase activity - a marker of Nrf2 activation (r = - 0.68, P<0.01). For change from baseline of PBMC gene expression with tRES-HESP treatment (assessed by the Nanostring method), change in area-under-the-curve plasma glucose (ΔAUGg) during oral glucose tolerance tests correlated negatively with change in Glo1 expression (r = - 0.56, P<0.05) and correlated positively with change in expression of thioredoxin interacting protein (TXNIP) (r = 0.59, P<0.05). In reverse translational studies, we found tRES-HESP decreased TXNIP expression by 39 ± 1% (P<0.001) in human hepatocyte-like HepG2 cells and 14 ± 3% in BJ fibroblasts in vitro (P<0.01). tRES-HESP may decrease TXNIP expression by decreasing the MG-driven UPR and by direct Nrf2-driven down regulation. TXNIP is a mediator of insulin resistance in liver and skeletal muscle and impaired pancreatic beta-cell insulin secretion. tRES-HESP is suitable for further evaluation for prevention and treatment of type 2 diabetes where decreased TXNIP may contribute to the therapeutic response. Disclosure M. Xue: None. M. Weickert: None. N. Rabbani: None. P. Thornalley: None. Funding Qatar Foundation; Qatar University

PULSE WAVE REFLECTION AND GENDER DIFFERENCE IN OBESE INDIVIDUALS

Objective: Although obesity is considered a cardiovascular risk factor due to its association with metabolic syndrome, recent studies in obese subjects with heart failure have shown that they have reduced adverse outcomes compared to non-obese individuals. This is consistent with the “obesity paradox”. However, body mass index (BMI) conventionally used to classify obesity, does not distinguish body shape or body fat distribution. This study aimed to explore the association between BMI and/or central obesity parameters and measures of arterial hemodynamics to assess the effect of obesity on function of large arteries. Design and method: Data was obtained from 832 normal individuals and stable patients with regular heart rate attending an outpatient health assessment clinic at Ruijin North Hospital, Shanghai. Subjects were divided into 3 groups according to their Body Mass Index (BMI < 24 normal, 24–28 overweight, > 28 obese; Chinese classification). Radial arterial waveforms and carotid-femoral pulse wave velocity (cfPWV) (SphygmoCor, AtCor Medical, Sydney) were measured with subjects recumbent, and calibrated to brachial cuff systolic (BSP) and diastolic pressure (BDP). Results: Central augmentation pressure (CAP), augmentation index (CAIx, a measure of wave reflection) and pressure amplification were lowest in the obese group (p < 0.001). BSP, CSP and cfPWV were highest in the overweight group, but only in females (p < 0.05). In males, CAP, CAIx and pressure amplification were significantly less as BMI increased (p < 0.05). In both sexes, central obesity measure of weight-to-height ratio (WHtR) was significantly different between BMI classes (p < 0.05). WHtR may be more appropriately correlated with hemodynamic parameters despite remaining differences between sexes (p < 0.05). Conclusions: Obesity in humans is associated with changes in the arterial pressure waveforms that are opposite of those usually described in aging and aortic stiffening. Differences are more obvious in males than females, and features of the “obesity paradox” are apparent when obesity is defined by BMI class only. Further study is warranted to investigate differences of associations between males and females, and effect of central obesity in males and females.

Effect of Obesity on Response to Spironolactone in Patients With Heart Failure With Preserved Ejection Fraction

Obesity is common in heart failure with preserved ejection fraction (HFpEF). Whether obesity modifies the response to spironolactone in patients with HFpEF remains unclear. We aimed to investigate the effect of obesity, defined by body mass index (BMI) and waist circumference (WC), on response to spironolactone in patients with HFpEF enrolled in Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. This was a post-hoc, exploratory analysis of the Americas cohort of Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. BMI≥30 kg/m2 was used to define the obese group and WC≥102 cm in men and ≥88 cm in women were defined as high WC. In separate analyses, BMI and WC were treated as continuous variables. The effect of spironolactone versus placebo on outcomes was calculated by BMI and WC using Cox proportional hazard models. Obese patients were younger and had more co-morbidities. In multivariate analysis, spironolactone use was associated with a significant reduction in the primary end point, compared with placebo in obese [hazard ratio (HR = 0.618, 95% CI 0.460 to 0.831, p = 0.001), but not in nonobese subjects (HR = 0.946, 95% CI 0.623 to 1.437, p = 0.796; p for interaction = 0.056). There was a linear association between continuous BMI and the effect of spironolactone, with the effect becoming significant at 33kg/m2. Similar results were obtained for the WC-based analysis. In conclusion, use of spironolactone in obese patients with HFpEF was associated with a decreased risk of the primary end point, cardiovascular death and HF hospitalizations, compared with placebo. Further prospective randomized studies in obese subjects are required.

Characterizing Effects of Antidiabetic Drugs on Heart Rate, Systolic and Diastolic Blood Pressure.

A model-based meta-analysis was performed with reported data from obese subjects and patients with type 2 diabetes (T2DM) to characterize the effects of dipeptidyl peptidase 4 (DPP4) inhibitors, gastric inhibitory polypeptides (GIPs), glucagon-like peptide-1 (GLP1), and dual GIP/GLP1 agonists, or a combination of these antidiabetic drugs (ADs) on heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP). A systematic literature search and review after the Cochrane method identified sources for investigational and approved ADs resulted in a comprehensive database with data from 178 clinical studies in obese subjects and patients with T2DM. Results indicated that there were AD class-dependent effects on HR and SBP, whereas no clear AD-related effects on DBP were found. All AD classes, except for DPP4 inhibitors, increased HR. The largest increase of 12bpm was seen with GLP1 receptor agonists. All AD classes appeared to decrease SBP. DPP4 inhibitors were associated with a marginal decrease of ~1mmHg, whereas GLP1 and GIP/GLP1 dual agonists exhibited the largest decrease of ~3mmHg in SBP. AD-related effects were similar in obese subjects and patients with T2DM. In conclusion, there are clinically relevant AD-related effects on both HR and SBP, but not on DBP. DPP4 inhibitors are associated with the smallest (if at all) effects on HR and SBP, whereas GLP1 inhibitors exhibited the largest effects on these two cardiovascular end points. Additional studies are warranted to further investigate how AD-related SBP decreases combined with HR increases affect long-term cardiovascular mortality.

Dexmedetomidine Improves Cardiovascular and Ventilatory Outcomes in Critically Ill Patients: Basic and Clinical Approaches.

Dexmedetomidine (DEX) is a highly selective α2-adrenergic agonist with sedative and analgesic properties, with minimal respiratory effects. It is used as a sedative in the intensive care unit and the operating room. The opioid-sparing effect and the absence of respiratory effects make dexmedetomidine an attractive adjuvant drug for anesthesia in obese patients who are at an increased risk for postoperative respiratory complications. The pharmacodynamic effects on the cardiovascular system are known; however the mechanisms that induce cardioprotection are still under study. Regarding the pharmacokinetics properties, this drug is extensively metabolized in the liver by the uridine diphosphate glucuronosyltransferases. It has a relatively high hepatic extraction ratio, and therefore, its metabolism is dependent on liver blood flow. This review shows, from a basic clinical approach, the evidence supporting the use of dexmedetomidine in different settings, from its use in animal models of ischemia-reperfusion, and cardioprotective signaling pathways. In addition, pharmacokinetics and pharmacodynamics studies in obese subjects and the management of patients subjected to mechanical ventilation are described. Moreover, the clinical efficacy of delirium incidence in patients with indication of non-invasive ventilation is shown. Finally, the available evidence from DEX is described by a group of Chilean pharmacologists and clinicians who have worked for more than 10 years on DEX.

The Combination of Curcumin and Salsalate is Superior to Either Agent Alone in Suppressing Pro‐Cancerous Molecular Pathways and Colorectal Tumorigenesis in Obese Mice

High-fat diets (HFDs) and adiposity increase colorectal cancer risk, in part by elevating pro-inflammatory cytokines that activate pro-cancerous signaling pathways. Curcumin (CUR), a dietary polyphenol and salsalate (SAL), an non-steroidal anti-inflammatory drug (NSAID) lacking the gastrotoxicity of aspirin, each suppress inflammatory signaling, but via different cellular pathways. A/J mice (n=110) are fed a low-fat diet (LFD, 10% kcal), a HFD (60% kcal), a HFD containing 0.4% CUR, a HFD containing 0.3% SAL, or a HFD containing both agents (CUR/SAL). All mice receive six injections of azoxymethane. Compared to LFD-fed mice, HFD-fed mice display elevated colonic cytokines, crypt cell proliferation, and increased tumorigenesis (p < 0.05). CUR/SAL significantly reduces colonic cytokines (p < 0.01), suppresses activation of the PI3K/Akt/mTOR/NF-κB/Wnt pathways (p < 0.01), activates AMPK (p < 0.01), attenuates abnormal proliferation of the colonic mucosa (p < 0.05), and reduces tumor multiplicity and burden (p < 0.05), in comparison to the HFD control. In contrast, CUR or SAL alone does not suppress abnormal crypt cell proliferation or tumor multiplicity, and is largely ineffective in modifying activation of these signaling pathways. These observations demonstrate the superiority of the CUR/SAL over the individual agents and provide a scientific basis for future translational studies in obese subjects and/or those habitually consuming HFDs.

LIK066, a Dual SGLT1/2 Inhibitor, Reduces Weight and Improves Multiple Incretin Hormones in Clinical Proof-of-Concept Studies in Obese Patients With or Without Diabetes

Background: LIK066 is a potent dual inhibitor of SGLT1/2 (IC50: 20.6 and 0.58 nM for SGLT1 and SGLT2). We studied mechanistic effects of dual SGLT1/2 inhibition of SGLT1 in the gut and SGLT1/2 in the kidneys. Methods: Effects of LIK066 on weight, glucose and a variety of incretin hormones (GLP-1, PYY, GIP, glucagon, insulin) were investigated in: 1) a single dose cross-over study in T2DM, 2) a 14 day randomized, double-masked study in T2DM, 3) a 12-week randomized, double-masked, placebo-controlled study in obese subjects with normoglycemia (NG) or dysglycemia (DG; HbA1c: ≥5.7% and &amp;lt;10%). Results: LIK066 (2.5, 30, 300 mg single dose) significantly reduced glucose excursion and insulin secretion (p&amp;lt;0.01 at 30 and 300 mg) following oral glucose tolerance test (OGTT) in patients with T2DM (n=12), with the 300 mg dose completely suppressing glucose and insulin excursions. In patients with T2DM (n=30), LIK066 15 mg qd for 14 days reduced blood glucose (41 mg/dL by continuous glucose monitoring) and increased 24-hour urinary glucose excretion (100 g/d on day 14). Furthermore total GLP-1 and PYY increased (AUC0-3hrs &amp;gt;1.5-fold; p&amp;lt;0.05) post-OGTT, while GIP levels were reduced (&amp;gt;50%; p&amp;lt;0.05). In obese subjects (n=88), LIK066 150 mg qd for 12 weeks reduced weight by 5.70% (p&amp;lt;0.001) compared to placebo, with higher effects in DG (6.85%) vs. NG (4.55%). Additionally multiple metabolic parameters improved (reduced waist circumference, postprandial glucose and insulin, and increased postprandial glucagon). LIK066 was generally safe and well tolerated. The most common AEs were headache, flatulence and diarrhea. Conclusions: LIK066 treatment leads to favorable changes in a variety of metabolic hormones (increased GLP-1, PYY and glucagon, reduced GIP, glucose and insulin), all contributing to WL effects of LIK066. The dual inhibition of SGLT1/2 in both the gut and kidneys is an attractive strategy for obesity or diabetes treatment. Disclosure Y. He: None. W.G. Haynes: Employee; Self; AstraZeneca. C.D. Meyers: Employee; Self; Janssen Research &amp; Development. A. Amer: Employee; Self; Novartis Pharmaceuticals Corporation. Stock/Shareholder; Self; Novartis AG. Y. Zhang: Employee; Self; Novartis Pharmaceuticals Corporation. P.C. Mahling: None. A.E. Mendonza: None. S. Ma: None. W. Chutkow: Employee; Self; Novartis Pharmaceuticals Corporation. E.S. Bachman: None.

Iodine Status After Bariatric Surgery\u2014a Prospective 10-Year Report from the Swedish Obese Subjects (SOS) Study

ContextBariatric surgery can lead to nutrient deficiencies. Gastric by-pass (GBP) entails restriction and malabsorption, whereas, vertical banded gastroplasty (VBG) is only restrictive.ObjectiveThe objective of this study is to study whether GBP-patients develop iodine deficiency from malabsorption, and if GBP- and VBG-patients develop lower 24-h urinary iodine excretion (24-UIE) than obese non-operated controls (OB-controls) due to lower iodine intake.DesignThe Swedish Obese Subjects (SOS) study is a prospective, non-randomized study of 4047 obese patients included 1987–2001, who chose bariatric surgery or non-surgical treatment. SOS-groups were compared at baseline, after 2 and 10 years and with population-based subsamples (MONICA-controls).PatientsOne hundred eighty-eight GBP-patients were matched with 188 VBG-patients and 188 OB-controls and with three subgroups from 412 MONICA-controls.Main Outcome MeasurementsPrimary outcome was 24-UIE. Secondary outcomes were iodine intake, iodine supplementation, TSH, FT4, and thyroid morbidity.ResultsAt baseline, median 24-UIE was higher in GBP-patients, VBG-patients and OB-controls than in MONICA-controls (214, 201, 203 and 137 μg/day, p < 0.001). At 10 years, 24-UIE in GBP-patients (161 μg/day) and VBG-patients (149 μg/day) was lower compared with baseline (p < 0.01) and OB-controls (189 μg/day, p < 0.01), but similar to 24-UIE in MONICA-controls (137 μg/day). The 10-year-dietary iodine intake was similar in GPB-patients and OB-controls, but higher in VBG-patients. Iodine supplementation was taken by 0–9% in SOS-groups.ConclusionAfter surgery, GBP- and VBG-patients did not suffer from iodine deficiency, but both groups had lower iodine status than OB-controls. Dietary supplements recommended after bariatric surgery do not need to include iodine, in iodine sufficient countries.Trial Registrationclinicaltrials.gov: NCT01479452

Curcumin and normal functioning of joints: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No1924/2006.

Following an application from Suomen Terveysravinto Oy, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Finland, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to curcumin and normal functioning of joints. The food that is proposed as the subject of the health claim is curcumin. The Panel considers that curcumin is sufficiently characterised. The claimed effect proposed by the applicant is ‘normal functioning of joints by reducing the biomarkers of inflammation’. The target population proposed by the applicant is the general population. Upon a request from EFSA to clarify whether the claimed effect is related to the normal function of joints or rather to the reduction of inflammation, the applicant did not address this issue in the reply. The Panel assumes that the claimed effect refers to the maintenance of joint function. The Panel considers that maintenance of joint function is a beneficial physiological effect. The Panel considers that no conclusions can be drawn from 15 human intervention studies conducted in patients with osteoarthritis or rheumatoid arthritis and from one study in obese subjects on serum cytokines for the scientific substantiation of the claim. In the absence of evidence for an effect of curcumin on the normal function of joints in humans, the results of the human studies on curcumin pharmacokinetics, safety and mechanistic studies, the animal studies and the in vitro studies submitted by the applicant cannot be used as a source of data for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of curcumin and maintenance of joint function.

Role of Macrophage Migration Inhibitory Factor in Obesity, Insulin Resistance, Type 2 Diabetes, and Associated Hepatic Co-Morbidities: A Comprehensive Review of Human and Rodent Studies.

Obesity is associated with a chronic low-grade inflammatory state that drives the ­development of obesity-related co-morbidities such as insulin resistance/type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. This metabolic inflammation is thought to originate in the adipose tissue, which becomes inflamed and insulin resistant when it is no longer able to expand in response to excess caloric and nutrient intake. The production of inflammatory mediators by dysfunctional adipose tissue is thought to drive the development of more complex forms of disease such as type 2 diabetes and NAFLD. An important factor that may contribute to metabolic inflammation is the cytokine macrophage migration inhibitory factor (MIF). Increasing evidence suggests that MIF is released by adipose tissue in obesity and that it is also involved in metabolic and inflammatory processes that underlie the development of obesity-related pathologies. This review provides a comprehensive summary of our current knowledge on the role of MIF in obesity, its production by adipose tissue, and its involvement in the development of insulin resistance, type 2 diabetes, and NAFLD. We discuss the main findings from recent clinical studies in obese subjects and weight-loss intervention studies as well as results from clinical studies in patients with insulin resistance and type 2 diabetes. Furthermore, we summarize findings from experimental disease models studying the contribution of MIF in obesity and insulin resistance, type 2 diabetes, and hepatic lipid accumulation and fibrosis. Although many of the findings support a pro-inflammatory role of MIF in disease development, recent reports also provide indications that MIF may exert protective effects under certain conditions.

Altered functional connectivity within the central reward network in overweight and obese women.

Background/Objectives:Neuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network.Subjects/Methods:Fifty healthy, premenopausal women, 19 overweight and obese (high BMI=26–38 kg m−2) and 31 lean (BMI=19–25 kg m−2) were selected from the University of California Los Angeles' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined.Results:GMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects with high BMI had greater connectivity of the left NAcc with bilateral ACC (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03) in a high frequency band.Conclusions:Overweight and obese women in the absence of food-related stimuli show significant structural and functional alterations within regions of reward-related brain networks, which may have a role in altered ingestive behaviors.

Obese subjects involvement in a population-based survey: the use of information and communication technologies (ICT) to avoid stigmatization.

Epidemiological and health promotion studies in obese subjects are hampered by the difficulty of obtaining a representative sample from the community. The enrollment process can be at high risk of stigmatization. The purpose of this study is to describe an original information and communication technologies (ICT) strategy to get around these ethical and methodological difficulties. A multimedia campaign of communication was organized on the topic of overweight and quality of life (QoL). A specific website was developed to collect via a questionnaire QoL data as well as information related to patient's needs and health perception from participants. To promote the website, multiple information supports were largely diffused. Primary care professionals were solicited to enhance the enrollment. The campaign started with a press conference covered by the main television channels. The ICT-based approach allowed the participation of 4,155 subjects homogeneously distributed with respect to body mass index, age, gender and socioeconomic level. A high percentage of subjects fully completed the web-based questionnaire. The press conference allowed reaching a quarter of the total sample within 5 days. Overweight remains a major public health problem. This survey showed that a holistic approach supported by ICT is a promising way to recruit obese subjects without stigmatizing the disorder.

Association of heart rate variability indices with inflammatory markers in non-diabetic obese dyslipidemic middle aged Saudi population

Background and Aim: It has been documented that obesity is associated with diabetes, hypertension and dyslipidemia that are known cardiovascular (CV) risks. However, there are few obese individuals, who do not develop diabetes early. In the present study, we have assessed the association of inflammatory markers in non-diabetic dyslipidemic obese subjects, as metabolic biomarkers have not been adequately studied in obesity without diabetes, especially in the assessment of CV risks. Methods: Twenty non-diabetic obese dyslipidemic subjects (study group) and 20 healthy non-obese subjects (control group) were included in this study. They were assessed for their body mass index (BMI) and heart rate variability (HRV) indices. Glucose, insulin, lipid profile and inflammatory markers were estimated from the fasting serum sample. Association of HRV with various parameters was determined by Pearson's correlation analysis. Results: The basal CV parameters, HRV, lipid profile, glucose, insulin and the inflammatory markers were significantly altered and correlated with ratio of low frequency to high frequency (LF: HF ratio), a marker of sympathovagal imbalance (SVI) in the study group when compared with the control group. Conclusion: SVI in the form of increased sympathetic and decreased parasymapathetic activity occurs in non-diabetic obese dyslipidemic subjects. Association of BMI, metabolic parameters and chronic low grade inflammation with LF: HF ratio may partly explain their augmented risks to future cardiac morbidities.

Correction: Gastric Bypass Surgery Is Followed by Lowered Blood Pressure and Increased Diuresis - Long Term Results from the Swedish Obese Subjects (SOS) Study

Correction: Gastric Bypass Surgery Is Followed by Lowered Blood Pressure and Increased Diuresis - Long Term Results from the Swedish Obese Subjects (SOS) Study

Evidenzbasierung von Maßnahmen zur Behandlung der Folgeerkrankungen kindlicher Adipositas

Childhood obesity is associated with cardiovascular events in adulthood. Multidisciplinary conventional obesity treatment programmes may reduce the body mass index standard deviation score at any age. However, over the years they lose their effectiveness especially during childhood. Only one study dealing with adult type2 diabetic patients could show persistent weight reduction over the period of 4years. Therefore, these conventional programmes may have short-term but no long-term influence on cardiovascular events. Bariatric surgery in childhood is exclusively performed in cases of morbid obesity. In adults, experience with regard to persistent weight loss has existed for over 20years now and has reached good therapeutic results in type2 diabetes. However, randomized and controlled long-term studies as to cardiovascular events and death do not exist. The Swedish Obese Subjects (SOS) study showed a significant decrease of cardiovascular events and death in the bariatric surgery study group compared to the conventional therapy group, but the groups were not randomized. The surgery group was younger and healthier compared to the conservatively treated group. The late start of therapy probably also had an unfavourable influence on cardiovascular events.

Cortisol, obesity, and the metabolic syndrome: A cross‐sectional study of obese subjects and review of the literature

Circulating cortisol and psychosocial stress may contribute to the pathogenesis of obesity and metabolic syndrome. To evaluate these relationships, we performed a cross-sectional study of 369 overweight and obese subjects and 60 healthy volunteers and reviewed the previous literature.Overweight and obese subjects had at least two other features of Cushing’s syndrome. They underwent measurements representing cortisol dynamics (24h urine cortisol excretion (UFC), bedtime salivary cortisol, 1 mg dexamethasone suppression test) and metabolic parameters (BMI, blood pressure (BP); fasting serum triglycerides, HDL, insulin, and glucose). Subjects also completed the Perceived Stress Scale (PSS). UFC, salivary cortisol and weight from 60 healthy volunteers were analyzed.No subject had Cushing’s syndrome. UFC and dexamethasone responses were not associated with BMI or weight. However, salivary cortisol showed a trend to increase as BMI increased (P< 0.0001), and correlated with waist circumference (WC) in men (rs=0.28, P=0.02) and systolic BP in women (rs=0.24, P =0.0008). Post-dexamethasone cortisol levels were weak to moderately correlated with fasting insulin (rs=− 0.31, P=0.01) and HOMA-IR (rs=−0.31, P=0.01) in men and systolic (rs=0.18, P= 0.02) and diastolic BP (rs=0.20, P=0.009) in women. PSS results were higher in obese subjects than controls, but were not associated with cortisol or metabolic parameters. As expected, WC correlated with fasting insulin, HOMA-IR and systolic BP (adjusted for BMI and gender; P < 0.01). Literature showed inconsistent relationships between cortisol and metabolic parameters.Taken together, these data do not support a strong relationship between systemic cortisol or stress and obesity or metabolic syndrome.

Bariatric Surgery and Long-Term Cardiovascular Events

Context Obesity is a risk factor for cardiovascular events. Weight loss might protect against cardiovascular events, but solid evidence is lacking. Objective To study the association between bariatric surgery, weight loss, and cardiovascular events. Design, Setting, and Participants The Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Patients were recruited between September 1, 1987, and January 31, 2001. Date of analysis was December 31, 2009, with median follow-up of 14.7 years (range, 0-20 years). Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Exclusion criteria were identical in surgery and control patients. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system. Physical and biochemical examinations and database cross-checks were undertaken at preplanned intervals. Main Outcome Measures The primary end point of the SOS study (total mortality) was published in 2007. Myocardial infarction and stroke were predefined secondary end points, considered separately and combined. Results Bariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio [HR], 0.47; 95% CI, 0.29-0.76; P = .002). The number of total first time (fatal or nonfatal) cardiovascular events (myocardial infarction or stroke, whichever came first) was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, 0.54-0.83; P Conclusion Compared with usual care, bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults.

Impact of Gastrointestinal Surgery on Cardiometabolic Risk

Bariatric surgery has gained acceptance as the only treatment with long-term efficacy for severe obesity. Recent publications emphasize the usefulness of bariatric surgery in the reduction of long-term cardiometabolic risk, cardiovascular disease incidence and mortality, and the management of uncontrolled type 2 diabetes (T2DM), an important cardiovascular risk factor in individuals with severe obesity. The present review article offers a brief overview of the literature published over the past several months relevant to cardiometabolic outcomes in bariatric surgery patients. A recent report from the Swedish Obese Subjects (SOS) study specifically reported a reduced incidence of cardiovascular events on long-term prospective follow-up after bariatric surgery. In addition, abundant studies have been recently published on gastric bypass surgery showing high T2DM remission rates as well as improved blood lipids and inflammatory markers after surgery. Sleeve gastrectomy is increasingly performed as a stand-alone operation. Recent reports on this surgery pertaining to cardiometabolic risk showed variable T2DM remission rates that may possibly be explained by age of the patients and duration of T2DM. Available data suggest a possible favorable impact of the surgery on CRP levels and improvements in the blood lipid profile. How sleeve gastrectomy compares to other surgical approaches will require further study. Biliopancreatic diversion with duodenal switch has been reported to offer some of the best long-term weight loss for obese patients. Approximately 9 out of 10 patients treated with this surgical procedure show long-term remission rates of T2DM. Significant improvements in the cardiometabolic risk profile are also observed after BPD-DS; they are especially pronounced regarding dyslipidemia. In conclusion, bariatric procedures improve the cardiometabolic risk profile, a phenomenon that appears to be only partly explained by the magnitude of the weight loss. Significant variations are observed with respect to the type of surgery and patient characteristics. More research is clearly needed on the short and long-term cardiometabolic outcome of obesity surgeries.