Ted D. Adams

Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient—2013 update: Cosponsored by american association of clinical endocrinologists, The obesity society, and american society for metabolic & bariatric surgery*

The development of these updated guidelines was commissioned by the AACE, TOS, and ASMBS Board of Directors and adheres to the AACE 2010 protocol for standardized production of clinical practice guidelines (CPG). Each recommendation was re‐evaluated and updated based on the evidence and subjective factors per protocol. Examples of expanded topics in this update include: the roles of sleeve gastrectomy, bariatric surgery in patients with type‐2 diabetes, bariatric surgery for patients with mild obesity, copper deficiency, informed consent, and behavioral issues. There are 74 recommendations (of which 56 are revised and 2 are new) in this 2013 update, compared with 164 original recommendations in 2008. There are 403 citations, of which 33 (8.2%) are EL 1, 131 (32.5%) are EL 2, 170 (42.2%) are EL 3, and 69 (17.1%) are EL 4. There is a relatively high proportion (40.4%) of strong (EL 1 and 2) studies, compared with only 16.5% in the 2008 AACE‐TOS‐ASMBS CPG. These updated guidelines reflect recent additions to the evidence base. Bariatric surgery remains a safe and effective intervention for select patients with obesity. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues.

Adipocyte iron regulates adiponectin and insulin sensitivity

Iron overload is associated with increased diabetes risk. We therefore investigated the effect of iron on adiponectin, an insulin-sensitizing adipokine that is decreased in diabetic patients. In humans, normal-range serum ferritin levels were inversely associated with adiponectin, independent of inflammation. Ferritin was increased and adiponectin was decreased in type 2 diabetic and in obese diabetic subjects compared with those in equally obese individuals without metabolic syndrome. Mice fed a high-iron diet and cultured adipocytes treated with iron exhibited decreased adiponectin mRNA and protein. We found that iron negatively regulated adiponectin transcription via FOXO1-mediated repression. Further, loss of the adipocyte iron export channel, ferroportin, in mice resulted in adipocyte iron loading, decreased adiponectin, and insulin resistance. Conversely, organismal iron overload and increased adipocyte ferroportin expression because of hemochromatosis are associated with decreased adipocyte iron, increased adiponectin, improved glucose tolerance, and increased insulin sensitivity. Phlebotomy of humans with impaired glucose tolerance and ferritin values in the highest quartile of normal increased adiponectin and improved glucose tolerance. These findings demonstrate a causal role for iron as a risk factor for metabolic syndrome and a role for adipocytes in modulating metabolism through adiponectin in response to iron stores.

Effect of Roux-en-Y Gastric Bypass Surgery on the Sex Steroids and Quality of Life in Obese Men

CONTEXT The effect of bariatric surgery on the reproductive function of obese men is not entirely elucidated. OBJECTIVE The aim of the study was to define the effect of Roux-En-Y gastric bypass surgery on the reproductive hormones and sexual function in obese men. DESIGN AND SETTING The cohort was followed for 2 yr at a clinical research center. PATIENTS Sixty-four severely obese men (22 who had gastric bypass surgery and 42 controls) participated in the study. INTERVENTION(S) Anthropometrics [weight, body mass index (BMI), and percentage body fat] and reproductive hormones were measured. The sexual quality of life was assessed using the Impact of Weight on the Quality Of Life-Lite questionnaire. MAIN OUTCOME MEASURE(S) Reproductive hormones and sexual quality of life were measured. RESULTS The mean age was 48.9 +/- 1.2 yr. At baseline, mean weight was 333.0 +/- 7.1 lb, BMI was 46.2 +/- 0.9 kg/m(2), and total testosterone was 339.9 +/- 21.32 ng/dl. BMI correlated positively with estradiol and negatively with total and free testosterone. Indices of dissatisfaction with sexual quality of life correlated positively with measures of obesity. Difficult sexual performance and low sexual desire correlated negatively with free and total testosterone (r = -0.273, P = 0.038; and r = -0.267, P = 0.042, respectively). After 2 yr, the gastric bypass surgery group had a significant decrease in BMI (-16.6 +/- 1.2 vs. -0.46 +/- 0.51 kg/m(2)) and estradiol (-8.1 +/- 2.4 vs. 1.6 +/- 1.4 pg/ml) and had an increase in total testosterone (310.8 +/- 47.6 vs. 14.2 +/- 15.3 ng/dl) and free testosterone (45.2 +/- 5.1 vs. -0.4 +/- 3.0 pg/ml). Sexual quality of life was improved after gastric bypass surgery. CONCLUSION Hormonal alterations and diminished sexual quality of life among obese men are related to degree of obesity, and both are improved after gastric bypass surgery.

Obesity and Sexual Quality of Life

Objectives: Reduced sexual quality of life is a frequently reported yet rarely studied consequence of obesity. The objectives of this study were to 1) examine the prevalence of sexual quality‐of‐life difficulties in obese individuals and 2) investigate the association between sexual quality of life and BMI class, sex, and obesity treatment—seeking status.

Left Ventricular Hypertrophy in Severe Obesity: Interactions Among Blood Pressure, Nocturnal Hypoxemia, and Body Mass

Obese subjects have a high prevalence of left ventricular (LV) hypertrophy. It is unclear to what extent LV hypertrophy results directly from obesity or from associated conditions, such as hypertension, impaired glucose homeostasis, or obstructive sleep apnea. We tested the hypothesis that LV hypertrophy in severe obesity is associated with additive effects from each of the major comorbidities. Echocardiography and laboratory testing were performed in 455 severely obese subjects with body mass index 35 to 92 kg/m2 and 59 nonobese reference subjects. LV hypertrophy, defined by allometrically corrected (LV mass/height2.7), gender-specific criteria, was present in 78% of the obese subjects. Multivariable regression analyses showed that average nocturnal oxygen saturation <85% was the strongest independent predictor of LV hypertrophy (P<0.001), followed by systolic blood pressure (P<0.015) and then body mass index (P<0.05). With regard to LV mass, there were synergistic effects between hypertension and body mass index (P interaction <0.001) and between hypertension and reduced nocturnal oxygen saturation. Severely obese subjects had normal LV endocardial fractional shortening (35±6% versus 35±6%) but mildly decreased midwall fractional shortening (15±2% versus 17±2%; P<0.001), indicating subtle myocardial dysfunction. In conclusion, more severe nocturnal hypoxemia, increasing systolic blood pressure, and body mass index are all independently associated with increased LV mass. The effects of increased blood pressure seem to amplify those of sleep apnea and more severe obesity.

Association of the FTO gene with BMI.

Variants in the FTO gene have been strongly associated with obesity in a very large sample (38,759) of diabetic and control subjects. To replicate these findings, the previously reported SNP in the FTO gene (rs9939609, T/A) was genotyped in 5,607 subjects from five different Utah studies. The studies included a random sample of the Utah population, families selected for aggregation of extreme thinness, families selected for severe obesity, a series of unrelated severe obesity subjects, and families participating in a 25‐year longitudinal study of cardiovascular disease and aging. Results show a strong significant increase in the rs9939609 A allele frequency with increasing BMI (P < 0.0001). In the longitudinal study, FTO genotypes were significantly associated with BMI at a baseline exam, a 2½‐year follow‐up exam and a 25‐year follow‐up exam using an additive genetic model. The mean genotype difference in BMI ranged from 1.3 to 2.1 kg/m2 across exams. The genotype difference in BMI means was established in youth, and at‐risk subjects under age 20 at baseline had a significantly larger 25‐year BMI increase (10.0 for A/A; 9.7 for A/T, and 8.5 kg/m2 for T/T, P = 0.05). We conclude that the BMI increases associated with FTO genotypes begin in youth and are maintained throughout adulthood.

Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese

Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight‐loss intervention. Three groups of severely obese subjects (N = 1,156, BMI ≥ 35 kg/m2) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population‐based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes‐related variables, resting metabolic rate (RMR), sleep apnea, and health‐related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF‐36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux‐en‐Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight‐loss intervention was highly effective for weight loss, improved health‐related quality of life, and resolution of major obesity‐associated complications measured at 2 years.

Health-related Quality of life in patients seeking gastric bypass surgery vs non-treatment-seeking controls

Background: Previous research has found that health-related quality of life (HRQOL) differs among obese individuals depending on treatment-seeking status, with greater impairments found in obese individuals seeking treatments of greatest intensity. The goals of this study were to determine: 1) if there are differences in obesity-specific HRQOL between seekers of gastric bypass surgery and non-treatment-seeking controls; and, 2) if the presence and number of co-morbid conditions impacts on HRQOL. Methods: Participants were 339 surgical cases (mean age 42.9, mean BMI 47.7, 85.5% women) and 87 controls (mean age 48.8, mean BMI 43.5, 71.3% women). Obesity-specific HRQOL was assessed using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite). Subjects were given a detailed medical history to determine the presence of co-morbid conditions. Results: After controlling for BMI, age, and gender, obesity-specific HRQOL was significantly more impaired (P<.001) in the surgery-seeking group than in the control group on all 5 scales and total score of the IWQOL-Lite. For total score, physical function and sexual life, there was increasing impairment with increasing number of co-morbid conditions. Treatment-seeking status, BMI, gender, and the presence of depression accounted for most of the variance in IWQOL-Lite total score. Conclusions: Persons seeking gastric bypass expe rience poorer HRQOL than non-treatment-seeking individuals after controlling for BMI, age, and gender. The presence of co-morbid conditions contributes to some aspects of HRQOL impairment.

Six-year changes in health-related quality of life in gastric bypass patients versus obese comparison groups

BACKGROUND Few studies have evaluated the long-term outcomes of bariatric surgery patients in relation to obese individuals not participating in weight loss interventions. Our objective was to evaluate the 6-year changes in health-related quality of life (HRQOL) in gastric bypass (GB) patients versus 2 obese groups not undergoing surgical weight loss. The study setting was a bariatric surgery practice. METHODS A total of 323 GB patients were compared with 257 individuals who sought but did not undergo gastric bypass and 272 population-based obese individuals using weight-specific (impact of weight on quality of life-lite) and general (medical outcomes study short-form 36 health survey) HRQOL questionnaires at baseline and 2 and 6 years later. RESULTS At 6 years, compared with the controls, the GB group exhibited significant improvements in all domains of weight-specific and most domains of general HRQOL (i.e., all physical and some mental/psychosocial). The 6-year percentage of excess weight loss correlated significantly with improvements in both weight-specific and physical HRQOL. The HRQOL scores were fairly stable from 2 to 6 years for the GB group, with small decreases in HRQOL corresponding to some weight regain. CONCLUSIONS GB patients demonstrated significant improvements in most aspects of HRQOL at 6 years compared with 2 nonsurgical obese groups. Despite some weight regain and small decreases in HRQOL from 2 to 6 years postoperatively, the HRQOL was relatively stable. These results support the effectiveness of weight loss achieved with gastric bypass surgery for improving and maintaining long-term HRQOL.

The ATGL Gene Is Associated With Free Fatty Acids, Triglycerides, and Type 2 Diabetes

Adipose triglyceride lipase (ATGL) was recently described to predominantly perform the initial step in triglyceride hydrolysis and therefore seems to play a pivotal role in the lipolytic catabolism of stored fat in adipose tissue. In the first study investigating genetic variations within the ATGL gene in humans, 12 polymorphisms identified via sequencing and database search were studied in 2,434 individuals of European ancestry from Utah. These polymorphisms and their haplotypes were analyzed in subjects not taking diabetes medication for association with plasma free fatty acids (FFAs) as primary analysis, as well as triglycerides and glucose as a secondary analysis (n = 1,701, 2,193, or 2,190, respectively). Furthermore, type 2 diabetes (n = 342 of 2,434) was analyzed as an outcome. FFA concentrations were significantly associated with several single nucleotide polymorphisms (SNPs) of ATGL (P values from 0.015 to 0.00003), consistent with additive inheritance. The pattern was similar when considering triglyceride concentrations. Furthermore, two SNPs showed associations with glucose levels (P < 0.00001) and risk of type 2 diabetes (P < 0.05). Haplotype analysis supported and extended the shown SNP association analyses. These results complement previous findings of functional studies in mammals and elucidate a potential role of ATGL in pathways involved in components of the metabolic syndrome.