Manpreet S. Mundi

Storage of Circulating Free Fatty Acid in Adipose Tissue of Postabsorptive Humans Quantitative Measures and Implications for Body Fat Distribution

OBJECTIVE Preferential upper-body fat gain, a typical male pattern, is associated with a greater cardiometabolic risk. Regional differences in lipolysis and meal fat storage cannot explain sex differences in body fat distribution. We examined the potential role of the novel free fatty acid (FFA) storage pathway in determining body fat distribution in postabsorptive humans and whether adipocyte lipogenic proteins (CD36, acyl-CoA synthetases, and diacylglycerol acyltransferase) predict differences in FFA storage. RESEARCH DESIGN AND METHODS Rates of postabsorptive FFA (palmitate) storage into upper-body subcutaneous (UBSQ) and lower-body subcutaneous (LBSQ) fat were measured in 28 men and 53 premenopausal women. Stable and radiolabeled palmitate tracers were intravenously infused followed by subcutaneous fat biopsies. Body composition was assessed with a combination of dual-energy X-ray absorptiometry and computed tomography. RESULTS Women had greater FFA (palmitate) storage than men in both UBSQ (0.37 ± 0.15 vs. 0.27 ± 0.18 μmol · kg−1 · min−1, P = 0.0001) and LBSQ (0.42 ± 0.19 vs. 0.22 ± 0.11 μmol · kg−1 · min−1, P < 0.0001) fat. Palmitate storage rates were significantly greater in LBSQ than UBSQ fat in women, whereas the opposite was true in men. Plasma palmitate concentration positively predicted palmitate storage in both depots and sexes. Adipocyte CD36 content predicted UBSQ palmitate storage and sex-predicted storage in LBSQ fat. Palmitate storage rates per kilogram fat did not decrease as a function of fat mass, whereas lipolysis did. CONCLUSIONS The FFA storage pathway, which had remained undetected in postabsorptive humans until recently, can have considerable, long-term, and sex-specific effects on body fat distribution. It can also offer a way of protecting the body from excessive circulating FFA in obesity.

Endoscopic Sleeve Gastroplasty Alters Gastric Physiology and Induces Loss of Body Weight in Obese Individuals

BACKGROUND & AIMS: Although bariatric surgery is the most effective therapy for obesity, only a small proportion of candidates undergo this surgery. Endoscopic sleeve gastroplasty (ESG) is a minimally invasive procedure that reduces the size of the gastric reservoir. We investigated its durability and effects on body weight and gastrointestinal function in a prospective study of obese individuals. METHODS: Twenty‐five obese individuals (21 female; mean body mass index, 35.5 ± 2.6 kg/m2; mean age, 47.6 ± 10 years) underwent ESG with endoluminal creation of a sleeve along the gastric lesser curve from September 2012 through March 2015 at the Mayo Clinic in Rochester, Minnesota. Subjects were followed for a median period of 9 months. We measured changes in body weight and recorded adverse events; patients were assessed by endoscopy after 3 months. Four participants underwent pre‐ESG and post‐ESG analyses to measure solid and liquid gastric emptying, satiation (meal tolerance), and fasting and postprandial levels of insulin, glucose, and gut hormones. RESULTS: Subjects had lost 53% ± 17%, 56% ± 23%, 54% ± 40%, and 45% ± 41% of excess body weight at 6, 9, 12, and 20 months, respectively, after the procedure (P < .01). Endoscopy at 3 months showed intact gastroplasty in all subjects. After ESG, physiological analyses of 4 participants showed a decrease by 59% in caloric consumption to reach maximum fullness (P = .003), slowing of gastric emptying of solids (P = .03), and a trend toward increased insulin sensitivity (P = .06). Three patients had serious adverse events (a perigastric inflammatory collection, a pulmonary embolism, and a small pneumothorax) but made full recoveries with no need for surgical interventions. No further serious adverse events occurred after the technique was adjusted. CONCLUSIONS: ESG delays gastric emptying, induces early satiation, and significantly reduces body weight. ESG could be an alternative to bariatric surgery for selected patients with obesity. ClincialTrials.gov number: NCT 01682733.

Free Fatty Acid Storage in Human Visceral and Subcutaneous Adipose Tissue: Role of Adipocyte Proteins

OBJECTIVE Because direct adipose tissue free fatty acid (FFA) storage may contribute to body fat distribution, we measured FFA (palmitate) storage rates and fatty acid (FA) storage enzymes/proteins in omental and abdominal subcutaneous fat. RESEARCH DESIGN AND METHODS Elective surgery patients received a bolus of [1-14C]palmitate followed by omental and abdominal subcutaneous fat biopsies to measure direct FFA storage. Long chain acyl-CoA synthetase (ACS) and diacylglycerol acyltransferase activities, CD36, fatty acid-binding protein, and fatty acid transport protein 1 were measured. RESULTS Palmitate tracer storage (dpm/g adipose lipid) and calculated palmitate storage rates were greater in omental than abdominal subcutaneous fat in women (1.2 ± 0.8 vs. 0.7 ± 0.4 μmol ⋅ kg adipose lipid−1 ⋅ min−1, P = 0.005) and men (0.7 ± 0.2 vs. 0.2 ± 0.1, P < 0.001), and both were greater in women than men (P < 0.0001). Abdominal subcutaneous adipose tissue palmitate storage rates correlated with ACS activity (women: r = 0.66, P = 0.001; men: r = 0.70, P = 0.007); in men, CD36 was also independently related to palmitate storage rates. The content/activity of FA storage enzymes/proteins in omental fat was dramatically lower in those with more visceral fat. In women, only omental palmitate storage rates were correlated (r = 0.54, P = 0.03) with ACS activity. CONCLUSIONS Some adipocyte FA storage factors correlate with direct FFA storage, but sex differences in this process in visceral fat do not account for sex differences in visceral fatness. The reduced storage proteins in those with greater visceral fat suggest that the storage factors we measured are not a predominant cause of visceral adipose tissue accumulation.

Body Fat Distribution, Adipocyte Size, and Metabolic Characteristics of Nondiabetic Adults

CONTEXT It is unclear whether adipocyte size or body fat distribution is most strongly linked to the metabolic complications of obesity. OBJECTIVE Our objective was to test whether adipocyte size better predicts metabolic characteristics of obesity than body composition. DESIGN, PARTICIPANTS, AND SETTING We analyzed the relationship between metabolic and anthropometric data collected from 432 largely Caucasian research volunteers (264 women) participating in studies conducted in the Mayo General Clinical Research Center between 1995 and 2008. MAIN OUTCOME MEASURES Metabolic variables included fasting plasma glucose, insulin, and triglyceride concentrations. Anthropometric variables included body composition, fat distribution, and sc abdominal and femoral adipocyte size. RESULTS Using both univariate and multivariate regression analysis, fasting triglyceride in both men and women was best predicted by computed tomography of visceral fat area. Fasting insulin concentrations were best predicted by sc abdominal fat area in women (r(2) = 0.40; P < 0.01) and body mass index in men (r(2) = 0.53; P < 0.0001); adipocyte size did not contribute independently. In men, fasting glucose concentrations were predicted by femoral adipocyte size (partial r(2) = 0.07; P = 0.002), body mass index (partial r(2) = 0.03; P = 0.07), and age (partial r(2) = 0.02; P = 0.06). In women, fasting glucose was predicted by abdominal sc fat area (partial r(2) = 0.12; P < 0.0001) and age (partial r(2) = 0.03; P = 0.01). CONCLUSIONS Our hypothesis that adipocyte size is the best predictor of metabolic characteristics was not supported in this population. The alternative explanation is that fat mass and body fat distribution have more influence on metabolic responses than adipocyte size.

Storage Rates of Circulating Free Fatty Acid Into Adipose Tissue During Eating or Walking in Humans

We measured subcutaneous adipose tissue free fatty acid (FFA) storage rates in postprandial and walking conditions to better understand the contributions of this pathway to body fat distribution. Palmitate tracers were infused intravenously and fat biopsies collected to measure palmitate storage in upper- (UBSQ) and lower-body subcutaneous (LBSQ) fat in 41 (17 men) and 40 (16 men) volunteers under postprandial and under postabsorptive walking conditions, respectively. Postprandial palmitate storage was greater in women than men in UBSQ (0.50 ± 0.25 vs. 0.33 ± 0.37 μmol ⋅ kg fat−1 ⋅ min−1; P = 0.007) and LBSQ fat (0.37 ± 0.25 vs. 0.22 ± 0.20 μmol ⋅ kg fat−1 ⋅ min−1; P = 0.005); storage rates were significantly greater in UBSQ than LBSQ fat in both sexes. During walking, UBSQ palmitate storage did not differ between sexes, whereas LBSQ storage was greater in women than men (0.40 ± 0.22 vs. 0.25 ± 0.15 μmol ⋅ kg fat−1 ⋅ min−1; P = 0.01). In women only, walking palmitate storage was significantly greater in LBSQ than UBSQ fat. Adipocyte CD36 and diacylglycerol acyltransferase (DGAT) correlated with LBSQ palmitate storage in the postprandial and walking condition, respectively. We conclude that UBSQ fat is the preferred postprandial FFA storage depot for both sexes, whereas walking favors storage in LBSQ fat in women. Transmembrane transport (CD36) and esterification into triglycerides (DGAT) may be rate-limiting steps for LBSQ FFA storage during feeding and exercise.

Bariatric surgery and diabetes: Implications of type 1 versus insulin-requiring type 2

To report the impact of bariatric surgery on metabolic outcomes in patients with type 1 diabetes (DM1) versus insulin‐requiring type 2 diabetes mellitus (IRDM2).

Increased Force Required With Proposed Standardized Enteral Feed Connector in Blenderized Tube Feeding.

BACKGROUND Enteral tube misconnections resulting in enteral nutrition being provided into the wrong port or tube has been increasingly reported, prompting the development of new international design standards for medical device tubing connectors. METHODS Four sample enteral feeds with varying viscosity were placed into a syringe with either the current feeding connector or a prototype ENFit connector. The force (N) required to compress the syringe was gathered through a dynamic mechanical analyzer (RSA G2 Solids Analyzer; TA Instruments). RESULTS The force needed to compress the syringe was lowest with a fiber-containing formula (Jevity 1 Cal, Abbott Nutrition, Columbus, OH), and a decline in force was detected with the ENFit compared with the current connector (8.61 ± 0.27 N vs 9.62 ± 0.23 N, P < .001). A commercial blenderized formula (Liquid Hope, Functional Formularies, Centerville, OH) required slightly higher force with the ENFit than the current connector (16.82 ± 1.23 N vs 14.5 ± 0.03 N, P < .001). Another commercial blenderized formula (Salmon, Oats, & Squash, Real Food Blends, Chesterton, IN) and a homemade blenderized recipe required significantly more force with the ENFit than the current tube (34.12 ± 0.95 N vs 22.91 ± 0.06 N, P < .001; 34.95 ± 0.06 N vs 27.72 ± 0.07 N, P < .001, respectively). CONCLUSION ENFit adapter implementation is the largest change to home enteral nutrition in more than a decade. Additional rigorous testing is required to ensure that the needs of all patients receiving home enteral nutrition are met prior to widespread adoption.

Prevalence of Home Parenteral and Enteral Nutrition in the United States

Background: Malnutrition is highly prevalent and associated with increased morbidity and mortality. Studies continue to reveal significant clinical benefits with nutrition support, including improved wound healing, reduction in complications and length of stay, and mortality. Due to these benefits, the prevalence of home parenteral and enteral nutrition (HPEN) continues to increase worldwide. In the United States, given our healthcare insurance landscape, it has been very difficult to ascertain the true prevalence of HPEN. Methods: Medicare beneficiary data for 2013 were obtained from Centers for Medicare and Medicaid Services. Commonly used Healthcare Common Procedure Coding System codes were used for home enteral nutrition (HEN) and home parenteral nutrition (HPN). Data regarding number of patients and insurance providers were also obtained from 3 of the largest home infusion providers in the United States (Coram CVS, Option Care Enterprises, and BioScrip Inc). Based on the ratio of Medicare to non-Medicare billing, an estimate of HPEN prevalence was obtained. Results: For 2013, there were 6778 Medicare beneficiaries for HPN and 114,287 for HEN. The ratio of Medicare to non-Medicare was 0.271 for HPN and 0.261 for HEN, leading to an estimated prevalence of 25,011 patients receiving HPN (79 per million U.S. inhabitants) and 437,882 patients receiving HEN (1385 per million U.S. inhabitants). There are an estimated 4129 pediatric patients and 20,883 adult patients receiving HPN; for HEN, 189,036 pediatric patients and 248,846 adult patients. Conclusion: Compared with results from 1992, the prevalence of HEN has increased dramatically, while the prevalence of HPN has declined.

Catheter Salvage After Catheter-Related Bloodstream Infection During Home Parenteral Nutrition.

Background: Catheter-related bloodstream infection (CRBSI) is a common complication in patients receiving home parenteral nutrition (HPN). Data regarding catheter salvage after a CRBSI episode are limited. We aimed to determine the incidence of CRBSI and rates of catheter salvage in adult patients receiving HPN. Materials and Methods: We retrospectively searched our prospectively maintained HPN database for the records of all adult patients receiving HPN from January 1, 1990, to December 31, 2013, at our tertiary referral center. Data abstracted from the medical records included demographics, diseases, treatments, and outcomes. The incidence of CRBSI and rates of catheter salvage were determined. Results: Of 1040 patients identified, 620 (59.6%) were men. The median total duration on HPN was 124.5 days (interquartile range, 49.0–345.5 days). Mean (SD) age at HPN initiation was 53.3 (15.3) years. During the study period, 465 CRBSIs developed in 187 patients (18%). The rate of CRBSI was 0.64/1000 catheter days. Overall, 70% of catheters were salvaged (retained despite CRBSI) during the study period: 78% of infections with coagulase-negative staphylococci, 87% with methicillin-sensitive Staphylococcus aureus, and 27% with methicillin-resistant S aureus. The percentage of catheters salvaged was 63% from 1990 to 1994, 63% from 1995 to 1999, 61% from 2000 to 2004, 72% from 2005 to 2009, and 76% from 2010 to 2013. Conclusion: Catheter salvage is possible after a CRBSI episode. Since most episodes of CRBSI are caused by skin commensals, effective treatment without removal of the central venous catheter is possible in most cases.

Use of Blenderized Tube Feeding in Adult and Pediatric Home Enteral Nutrition Patients.

Background: Long-term use of enteral nutrition (EN) continues to increase due to significant noted benefits. Patients also continue to express significant desire to pursue holistic and organic diets. Despite this, many nutrition providers are not well versed in assisting patients with blenderized tube feeding (BTF), and prevalence of its use is unknown. Methods: A validated survey was administered to Oley Foundation members or individuals with access to the Oley website to assess the prevalence of BTF. Results: A total of 216 participants took the survey, of whom 125 (57.8%) were pediatric patients with a mean age of 5.4 ± 3.5 years and 91 (42.2%) were adults with a mean age of 51.7 ± 19.5 years. Of pediatric patients, 112 (89.6%) used BTF for an average of 71% of their total daily nutrition intake; 93 (83%) reported that BTF comprised >50% of their daily EN, 12 (10.7%) reported it comprised 25%–50% of their daily enteral intake, and 7 (6.3%) reported BTF comprised < 25% of their daily intake. In the adult population, 60 (65.9%) used BTF for an average of 56% of total daily nutrition intake; 41 (68.4%) reported BTF comprised >50% of their daily nutrition intake, 11 (18.3%) reported it compromised 25%–50%, and 8 (13.3%) reported BTF comprised <25% of their daily intake. Conclusions: Most of the pediatric and adult patients surveyed use BTF as some portion of their enteral intake, making it essential that clinicians expand their knowledge related to BTF to appropriately care for this patient population.