Category Archives: Nutrition

Should We Be Excited About a New Medication (Liraglutide) for Obesity?

Posted on by

Thus far, “the benefits of medications to treat obesity remain limited because of side effects and inadequate efficacy, especially in the long term.” This is part of an editorial (Siraj ES, Williams J. NEJM 2015; 373: 82-3) that explains a recent study (Pi-Sunyer X, et al. NEJM 2015; 373: 11-22). However, there is a huge need for a cost-effective medication because bariatric surgery is not feasible for 400 million obese persons worldwide.

Liraglutide (marketed as Victoza) has been approved by the FDA for weight loss in adults based on this published study and two other trials.  Liraglutide is a glucagon-like peptide-1 (GLP-1) mimetic.  The authors conducted a 56-week, double-blind trial with 3731 non-diabetic patients. In a 2:1 design, most patients received a once-daily subcutaneous 3.0 mg injection of liraglutide; some received placebo.  Both groups received lifestyle counseling.

Key finding:

  • At week 56, the treatment group had lost a mean of 8.4 kg compared with the placebo group which lost 2.8 kg.

There were similar rates of adverse events (mildly increased in treatment group); the rate of new diagnoses of diabetes was less than one-eighth that in the placebo group.  A 2-year extension trial is being analyzed to further pursue this finding.  Also, the authors note that 4 cases of breast cancer (0.2%) were detected in the treatment group compared with 1 (0.1%) in the placebo group.  This finding could have been due to easier exam following weight loss.  It is noted that the labeling for liraglutide has a black box warning regarding thyroid c-cell tumor risk which have occurred in rodents at clinically relevant doses.

A fairly good 2 minute summary: NEJM Short Take on Liraglutide

Despite the weight loss, the editorial has a cautious tone.

  • “There were statistically significant, although sometimes quantitatively modest, improvements in secondary end points, which included glycemic control, fasting insulin concentrations, cardiometabolic markers, and quality-of-life measures.”
  • “Most obese participants stayed obese, reversal of the metabolic syndrome was not quantified, and liraglutide may be required indefinitely, like statins, but with delivery by injection and at a nontrivial cost.”  According to http://www.goodrx.com, the approximate retail price is $596.01 for 18 mg. For type 2 diabetes, the dosage varies from 1.2 to 1.8 mg per day, after the first week which is dosed at 0.6 mg.

Take-home point: This new medication may help with modest weight loss but at a very significant cost.  In addition, long-term data are lacking. Thus, right now, this medication does not provide the cost-effective option to bariatric surgery.

Related blog posts:

Georgia Aquarium

Georgia Aquarium

Omega-3 Fatty Acids and Nonalcoholic Fatty Liver Disease

Posted on by

A recent study (Janczyk W. J Pediatr 2015; 166: 1358-63; editorial 1335-6) examines whether omega-3 fatty acid supplement would be helpful for overweight/obese children with nonalcoholic fatty liver disease (NAFLD).  This randomized controlled trial had 64 patients complete the study; the median age of enrolled patients was 13 years.

Free Full Text Article: Omega-3 Fatty Acids Therapy in Children with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

The treatment cohort received doscosahexaenoic acid (DHA) and eicosapenatenoic acid (EPA) at a dose of 450-1300 mg/day.

Key finding:

  • After 6 months, omega-3 fatty acid supplementation did not increase the number of patients with decreased ALT levels and it did not affect liver steatosis on ultrasound.

The editorial reviews a previous positive study for DHA supplementation from Italy (n=60) but notes that other larger trials in adults have not shown efficacy of omega-3 fatty acids (Gastroenterol 2014; 147: 377-84.e1, Hepatology 2014; 60: 1211-21). It could be that much longer studies will be needed to determine whether omega-3 fatty acids will be helpful.

Take-home message: Overall, the sum of these studies indicates that supplementation with omega-3 fatty acids has not been shown to be effective for NAFLD and it is not likely to be a significant breakthrough.  Even if it were shown to help modestly, would pediatric patients be placed on therapy indefinitely?

Briefly noted:

Kusters DM et al. “Efficacy and Safety of Ezetimibe Monotherapy in Children with Heterozygous Familial and Nonfamilial Hypercholesterolemia” J Pediatr 2015; 166: 1377-84.  Ezetimbe (10 mg), a cholesterol absorption inhibitor, lowered LDL by 27% after 12 weeks from baseline. It was well-tolerated

Complications with G-tube Placement

Posted on by

Two recent studies highlight the risks with gastrostomy tube (G-tube) placement.

  • McSweeney ME, et al. J Pediatr 2015; 166: 1514-9.
  • Jacob A, et al. J Pediatr 2015; 166: 1526-8.

The first study, a chart review of 591 patients, identified a 10.5% major complication rate and ~25% complication rate overall.  By far the most common complication for both major and minor complications was stoma infections.  In this study, the g-tube used was the Corflo PEG tubes using a pull-procedure.  Perioperative antibiotics (i.e. cefazolin for 24 hrs) were administered. Exchange of g-tubes (to a skin-level device) took place at 6 months in most patients.  Major complications were defined as an unplanned adverse event necessitating additional hospitalization, surgery or interventional procedure.

Key findings:

  • Cumulative incidence of major complications was 2.4% within 48 hours, 5.8% with 1 month, 9.2% within 6 months, and 14.7% at 12 months post-G-tube placement
  • Among the 62 patients experiencing major complications, 55 of the 72 were due to infections, 6 were dehiscence of PEG at exchange, 2 were due to granulation needing surgery, 2 were due to colon perforation, and 1 due to pneumoperitoneum.  Other major complications included: 1 aborted PEG procedure, 1 post-PEG cardiopulmonary arrest, 3 malfunctioning PEG tubes, and 1 failure to exchange PEG tube for a skin-level device.

Overall, this study shows a fairly high rate of significant complications and that their occurrence was usually not in the immediate post-operative period.

The second study was a prospective study of 183 children undergoing a one-step percutaneous G-tube using the MIC-KEY introducer kit.  This one-step button requires insertion of three gastropexy anchors, dilatation of gastrostomy tract, and button measurement.  The authors evaluated the safety technique and the learning curve.

Key Findings:

  • In the first 6-month period, the authors noted a 17% failure rate; this declined to 0-7% in the following 6-month study periods.
  • The time for placement improved from 21 minutes during the first 6-months to 12 minutes during the sixth 6-month study period
  • The authors highlighted several advantages: 1. lower peristomal infection rate (10.6% compared to their historical control of 29% with pull-PEG); the PEG avoids need to bypass the oropharynx. 2. One procedure/anesthetic for a skin-level device.
  • In the article, the results indicate that there are clearly tradeoffs for these advantages: after the initial learning curve, their remained complications in the majority (65%), mostly mild complications which included accidental button removal (35%), gastric heterotopy (24%), and peristomal leakage (15%).  Also, 35% of patients returned for a replacement tube before the planned date because of intragastric balloon deflation.
  • The cost savings with this one-step button were estimated to be 11% lower.

Bottomline: While g-tubes remain important in caring for children with feeding problems, there is not a magic bullet to eliminate complications.  Understanding the frequency of these problems and discussing them with families will help them be addressed promptly.

Related blog posts:

Resource:

www.feedingtubeawareness.com  This site contains a terrific PDF download which explains enteral tubes in an easy to understand style along with good graphics. “What You Need to Know Now, A Parent’s Introduction to Tube Feeding is the guidebook that every parent wished they had when they were first introduced to feeding tubes.”

Iron Deficiency Common in Patients Requiring Long-Term Parenteral Nutrition

Posted on by

A recent study (JPEN J Parenter Enteral Nutr May 13, 2015 0148607115587329) demonstates a high rate of iron deficiency anemia in patients requiring home parenteral nutrition (Thanks to Kipp Ellsworth for reference).

From Abstract:

Methods: Medical records of patients receiving HPN at the Mayo Clinic from 1977 to 2010 were reviewed. Diagnoses, time to IDA development, and hemoglobin, ferritin, and mean corpuscular volume (MCV) values were extracted. Response of iron indices to intravenous iron replacement was investigated.

Results: Of 185 patients (122 women), 60 (32.4%) were iron deficient…Of 93 patients who had sufficient iron storage, 37 had IDA development after a mean of 27.2 months (range, 2–149 months) of therapy. Iron was replaced by adding maintenance iron dextran to PN or by therapeutic iron infusion. Patients with both replacement methods had significant improvement in iron status. With intravenous iron replacement, mean ferritin increased from 10.9 to 107.6 mcg/L (P < .0001); mean hemoglobin increased from 11.0 to 12.5 g/dL (P = .0001); and mean MCV increased from 84.5 to 89.0 fL (P = .007).

Conclusions: Patients receiving HPN are susceptible to IDA. Iron supplementation should be addressed for patients who rely on PN.

Zoo Atlanta

Zoo Atlanta

 

The Upside of Too Much Screen Time

Posted on by

Briefly noted: A recent study (Campbell LB, et al. J Pediatr 2015; 166: 1505-13) has shown a reducing incidence of melanoma in children and adolescents in the U.S. during the 2000-2010 study period.  This study used data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry.  In adolescents, between 2003-2010, the rate of this very rare cancer decreased ~11% per year from 2003-2010.

While the authors do not know the reason for this improved trend, besides speculation about improved used of sunscreen, they also speculate that decreased time spent outdoors may be a factor.  My hunch is that this is a much more likely a contributor to this trend due to the pervasive nature of television, computers and other electronic devices.

Cumberland Island

Cumberland Island

 

How to Improve Food Selection at Schools

Posted on by

A recent study (Cohen JFW et al. JAMA Pediatr 2015; 169: 431-7; thanks to Ben Gold for this reference) showed both the short-term and long-term effects of targeted interventions to improve food selection at schools.

The Modifying Eating and Lifestyles at School Study (MEALS study) was a randomized trial in 2 urban, low-income school districts in Massachusetts.  After a one month baseline, there was an initial 3 month randomization period in which there were 4 “chef” schools and 10 control schools.  As you may have guessed, the “chef” schools were assigned a chef to improve food palatability and to teach the cafeteria staff.

The recipes are available at the following link: www. projectbread.org/reusable-components/accordions/download-files/school-food-cookbook.pdf.  The recipes in this cookbook are great if you need to put together meals serving 100.  Recipes include Cachupa, Quinoa, Squash, and Kale.

During the next study period of 4 months, both groups were further divided into schools with “smart cafe” design or control design.  The smart cafes encouraged both vegetable and fruit selection/healthy food selection:

  • Veggies offered at beginning of lunch line
  • Fruits placed in attractive containers
  • Fruit options placed by cashier
  • Improved signage and images promoting fruits and veggies
  • White milk placed in front of sugar-sweetened milk (eg. chocolate milk)

Did these interventions work?  Yes, pretty much.

  • After 3 months, vegetable selection increased in chef schools with odds ratio (OR) of 1.75
  • At conclusion of study, vegetable selection increased in the chef (OR 2.54), smart cafe (OR 1.91) and chef plus smart cafe (OR 7.38)
  • At conclusion of study, fruit selection increase in the chef (OR 3.08), smart cafe (OR 1.45) and chef plus smart cafe (OR 3.10)
  • Actual consumption (not just selection) increase in chef and chef plus smart cafe schools but there was no lasting effect of smart cafe by itself.  The amount of vegetable intake approximately doubled in the chef or chef plus smart cafe, consuming an additional 0.75 cups of vegetables per week.

Conclusions (from the authors): “While using choice architecture [i.e. smart cafe design] “may be a good short-term strategy to increase healthier food consumption, it does not appear to be a successful long-term strategy…This study also reaffirms that a chef intervention focusing on school food quality, palatability, and variety is an effective method …over time…This study also confirms the importance of repeated exposures to new school foods.”

Related blog posts:

Kori Bustard, Zoo Atlanta

Kori Bustard, Zoo Atlanta

Vitamin D in Preterm Infants

Posted on by

Vitamin D has garnered a great deal of attention due to concerns that deficiency worsens the outcomes in so many different conditions, including respiratory tract infections, inflammatory bowel disease, diabetes mellitus (type 1), multiple sclerosis, colorectal cancer, schizophrenia, depression, cardiovascular disease, hepatocellular carcinoma and other conditions.  However, evidence of causation is typically inconclusive.

For preterm infants, a study (Onwuneme C, et al. J Pediatr 2015; 166: 1175-80) notes an association between 25-hydroxy vitamin D (25OHD) levels drawn at 24 hours of life and acute respiratory morbidity.

In this study, levels were also drawn at the time of discharge in the 94 preterm infants.  In addition, maternal 25OHD) levels were checked 24 hours after delivery. These preterm infants were either <32 weeks gestation or <1.5 kg.  The study population was predominantly Caucasian.

Key findings:

  • 92% had 25OHD ≤20 ng/mL (=”<20 group”)
  • 64% had 25OHD ≤12 ng/mL (=”<12 group”)
  • Levels of 25OHD ≤12 ng/mL were associated with increased oxygen requirement (P=.008) and greater need for assisted ventilation (P=.013).  The odds of requiring assisted ventilation were approximately 3-fold higher.
  • The authors state that the baseline characteristics for the <12 group were similar to the <20 group.
  • There was statistical difference in the rate of NEC (Bell stage ≥1) based on the 25OHD levels (P=.048)

The authors note in their discussion that they favor supplementation with 400 IU/day which is in agreement with the American Academy of Pediatrics.  Previous ESPGHAN recommendations were 800-1000 IU/day for infants.

The authors note that 25OHD did not affect sepsis outcome.  In addition, antibiotics during labor was virtually identical between the two groups.  However, no data on CRP values were provided.

Bottomline: This study shows an association between 25OHD values and several important neonatal outcomes.  Whether 25OHD is a marker (eg. epiphenomenon) for these outcomes or whether low 25OHD contributes to these outcomes remains unclear.

Related blog posts:

 

Mediterranean Diet and Better Cognitive Function

Posted on by

The Mediterranean diet has been associated with a number of health benefits.  A recent study in JAMA Internal Medicine indicates that this diet may result in better cognitive function.

A summary of this study from NBC News: Diet That Helps You Live Longer May Keep Your Mind Sound

Here’s an excerpt:

They singled out 447 volunteers considered at high risk of heart disease. Heart disease and dementia are already linked — people with a higher risk of one usually have a higher risk of the other, also.

Two groups were assigned to follow the Mediterranean diet and told to add either five 5 tablespoons of extra virgin olive oil a day or a handful of mixed nuts. The third group got the low-fat advice….

The volunteers, who had an average age of 67, were tested from time to time on memory skills. The group who ate the extra nuts did better in terms of memory and the group given extra virgin olive oil performed better on tests that required quick thinking…

Just over 13 percent of those who got extra olive oil were diagnosed with mild cognitive impairment, which may or may not lead to Alzheimer’s disease. Just 7 percent of those who got nuts were diagnosed with mild cognitive impairment, while around 13 percent of those who got neither developed memory loss.

But many of the patients actually saw their memories get better over the four years. On average, those in the low-fat-only group lost some memory and thinking skills, but those who got extra nuts had their memory skills improve on average, while those who got olive oil had improvements in problem-solving and planning skills…

The findings fit in with research that has shown a Mediterranean-style diet can lower the risk of Alzheimer’s disease.

Related blog posts:

Zoo Atlanta, Eastern Diamond Rattlesnake

Zoo Atlanta, Eastern Diamond Rattlesnake

Reaching Consensus on Bariatric Intervention in Children and Adolescents

Posted on by

A recent medical position paper (Nobili V, et al. JPGN 2015; 60: 550-61) provides guidance for bariatric surgery intervention in children and adolescents with and without nonalcoholic fatty liver disease (NAFLD).

While the authors acknowledge that bariatric surgery can “dramatically reduce the risk of adulthood obesity and obesity-related diseases,” they advocate its use in adolescents with the following:

  • BMI >40 kg/m-squared with severe comorbidities: type 2 diabetes mellitus, moderate-to-severe sleep apnea, pseudotumor cerebri, or NASH with advanced fibrosis (ISHAK score >1)
  • BMI >50 kg/m-squared with mild comorbidities: hypertension, dyslipidemia, psychological distress, gastroesophageal reflux, anthropathies, NASH, impairment in activities of daily living, mild obstructive sleep apnea, panniculitis, chronic venous insufficiency, urinary incontinence
  • Additional criteria: have attained 95% of adult stature, failed behavioral/medical treatments, psychological evaluation perioperatively, avoid pregnancy for 1 year after surgery, will adhere to nutritional guidelines after surgery, informed assent from teenager (along with parental consent)

Key points:

  • “There is a lack of randomized controlled trials examining the effects of bariatric surgery on NAFLD or NASH.”  In Table 3, the authors provide a summary of 16 previous studies/outcomes; though none of the studies enrolled more than 60 patients.
  • In an adult prospective study with 381 patients (Mathurin P et al. Gastroenterol 2009; 137: 532-40), there was a significant decline in the severity/prevalence of steatosis and resolution of NASH at 1 and 5 years.
  • Bariatric surgery, in adult studies, have improved diabetes, insulin resistance, hypertension, and dyslipidemia.
  • Patients who have “undergone bariatric surgery show higher suicide rates than the general population.”  Psychological evaluation should be integrated with surgical decision.
  • Type of surgery: Roux-en-Y Gastric Bypass (RYGB) is favored by the authors; they also discuss studies with Laparoscopic Adjustable Gastric Banding (LAGB).  “RYGB and LAGB are the 2 main surgical procedures that have been used in pediatric obesity.  RYGB is considered a safe and effective option for adolescents with extreme obesity, as long as appropriate long-term follow-up is provided. LAGB has not been approved by Food and Drug Administration for use in adolescents, and there should be considered investigational only.”

It is interesting that the authors are so deferential to the Food and Drug Administration.  It is clear from their position paper that LAGB has similar evidence supporting its use in adolescents as RYGB.  They even note that it has potential for reversibility and “an excellent safety profile with a lower risk of postoperative vitamin deficiencies when compared with biliopancreatic diversion and RYGB.”

Bottomline: Given the continuation of the obesity epidemic, additional pediatric medical expertise will be needed to help evaluate adolescents for bariatric surgery and to follow them postoperatively.

Related blog posts:

Weight Loss Improves NASH

Posted on by

A recent study (http://dx.doi.org/10.1053/j.gastro.2015.04.005) helps confirm the notion that the most effective therapy for nonalcoholic steatohepatitis is weight loss. (From Rohit Kohli twitter feed).

Abstract:

Background & Aims

It is not clear how weight loss affects histologic features of liver in patients with nonalcoholic steatohepatitis (NASH). We examined the association between the magnitude of weight loss through lifestyle modifications and changes in histologic features of NASH.

Methods

We conducted a prospective study of 293 patients with histologically proven NASH who were encouraged to adopt recommended lifestyle changes to reduce their weight over 52 weeks, from June 2009 through May 2013, at a tertiary medical center in Havana, Cuba. Liver biopsies were collected when the study began and at week 52 of the diet, and analyzed histologically.

Results

Paired liver biopsies were available from 261 patients. Among 293 patients who underwent lifestyle changes for 52 weeks, 72 (25%) achieved resolution of steatohepatitis, 38 (47%) had reductions in NAFLD activity scores (NAS), and 56 (19%) had regression of fibrosis. At week 52, 88 subjects (30%) had lost 5% or more of their weight. Degree of weight loss was independently associated with improvements in all NASH-related histological parameters (odds ratios, 1.1–2.0;P<.01). A higher proportion of subjects with 5% weight loss or more had NASH resolution (51/88, 58%) and a 2-pt reduction in NAS (72/88, 82%) than subjects that lost less than 5% of their weight (P<.001). All patients who lost 10% of their weight or more had reductions NAS, 90% had resolution of NASH, and 45% had regression of fibrosis. All patients who lost 7%−10% of their weight and had few risk factors also had reduced NAS. In patients with baseline characteristics that included female sex, body mass index ≥35, fasting glucose >5.5 mmol/L, and many ballooned cells, NAS scores decreased significantly with weight reductions of 10% or more.

Conclusions

A greater extent of weight loss, induced by lifestyle changes, is associated with the level of improvement in histologic features of NASH. The highest rates of NAS reduction, NASH resolution, and fibrosis regression occurred in patients with weight losses of 10% or more.