Category Archives: Nutrition

Preventing Type 2 Diabetes

Posted on by

A ‘perspective’ article reviews data from several studies that show the efficacy of medical treatments aimed at preventing type 2 diabetes (NEJM 2012; 367: 1177-79).

The Diabetes Prevention Program (DPP) was a comparative effectiveness trial of 3234 overweight or obese adults with impaired glucose tolerance (prediabetes).  Findings from this study (published in 2002) showed that lifestyle intervention (attempts at weight loss through diet and exercise) reduced conversion to diabetes by 58% over 3 years, whereas metformin reduced this conversion by 31% over 2 years.  Lifestyle intervention worked best in patients ≥ 60 years.

Subsequently, 88% of these subjects were enrolled in the 10-year outcome study (DPPOS).  The lifestyle intervention group had a 31% 10-year reduction in diabetes compared with 18% for metformin.

The editorial points out that there have been efforts to expand these results across the country through CDC-sponsored programs in cooperation with the YMCA and UnitedHealth.

Potential roadblocks remain:

  • Most payers do not cover these preventive services.
  • US Preventive Services Task Force (USPSTF) has not issued a recommendation on these services.  this affects both public and private insurance coverage.
  • Metformin which may be useful in younger populations does not have a specific indication for diabetes prevention from the FDA (off-label use only).

Whether prevention is ‘worth a pound of cure’ may be hard to discern with prediabetes.    Since the peak incidence of diabetes is between 50 and 60 years and complications often emerge more than a decade later, the benefits of preventing diabetes may not be fully apparent for quite a long time.

Related blog entries:

Treating diabetes with surgery | gutsandgrowth

Lower leptin with physical activity | gutsandgrowth

Staggering cost of obesity | gutsandgrowth

Eliminating sweetened beverages to help obesity

Posted on by

For every difficult problem there’s a solution that’s simple, neat and wrong.–HL Mencken

Two studies from the New England Journal of Medicine, thus far (at the time of writing) published only online, shed some light on the difficult problem of consumption of sugar-sweetened beverages and its relationship to obesity:

  • A Trial of Sugar-free or Sugar-Sweetened Beverages and Body Weight in Children. Janne C. de Ruyter, M.Sc., et al. September 21, 2012DOI:  10.1056/NEJMoa1203034

  • A Randomized Trial of Sugar-Sweetened Beverages and Adolescent Body Weight. Cara B. Ebbeling, Ph.D., et al,  September 21, 2012DOI:  10.1056/NEJMoa1203388

The first study was an 18-month double-blind, randomized, controlled trial with 641 primarily normal-weight children between 4-12 years of age; patients were recruited from elementary schools.  Patients either received a sugar-free artificially sweetened beverage or a similar sugar-containing beverage, 8 oz per day at school.  At 18 months, 74% continued consuming these beverages; among those remaining in the program, on average, they consumed 83% of the assigned 7 cans each week.  Another marker of adherence was increased urinary sucralose in the sugar-free group (6.7 mg/L compared with 0.1 mg/L in the sugar group). Weight gain was less in the sugar-free group: 6.35 kg compared with 7.37 kg.  Other measures of weight gain were less as well, including skinfold-thickness, waist-to-height ratio, and fat mass. It is also noted that in the U.S. the average consumption of sweetened beverages is three times the amount noted in this Dutch study.

The second study examined 224 overweight and obese adolescents who were randomly assigned into experimental and control groups.  The experimental group received a 1-year intervention designed to decrease consumption of sugar-sweetened beverages; they were followed for an additional year afterwards.  Retention rates were good: 93% at 2 years. To support the experimental group, sugar-free beverages were delivered to  the house and the families received monthly motivational calls. In addition, patients had three check-in visits and written materials. The consumption of sugar-sweetened beverages declined in the experimental group from a baseline of 1.7 servings per day to nearly 0 at 1 year & remained lower at 2 years than the control group.  The primary outcome, BMI, did not differ significantly between the two groups at 2 years nor did change in body fat percentage.  (BMI did improve at 1 year, -0.57.)  In the small number of Hispanic participants (n=27 in experimental group), there was a significant change in BMI at both 1 and 2 years.

While consumption of sugar-sweetened beverages have been considered to be more fattening than solid foods because they do not lead to a sense of satiety, it appears that restriction of these beverages by itself will not make a major dent in the problem of obesity.

Related blog posts:

NAFLD Guidelines 2012

Treating diabetes with surgery

Lower leptin with physical activity

Staggering cost of obesity

Psychology of obesity and food addiction

Weight of the Nation

Cardiovascular disease for the entire family

TODAY is worrisome for a lot of tomorrows

TPN cycling

Posted on by

A randomized prospective study of early parenteral nutrition cycling was not helpful in reducing parenteral nutrition associated cholestasis (PNAC): J Pediatr 2012; 161: 229-33.

This study enrolled preterm infants <1250 g in the first five postnatal days to either cycled (n=34) or continuous parenteral nutrition (n=36).  Cholestasis was defined as direct bilirubin >2 mg/dL. The study indicated that intralipid 20% was administered in all patients over 18 hours; the exact amount is not clear, though in the cycled group, patients received 3 g/kg/day on postnatal day 3.9 ± 2.6.  All patients received dextrose over 24 hours; only the amino acid (TrophAmine) infusion varied: 20 hours compared with 24 hours.

  • PNAC in each group was nearly identical, 32% vs 31% as were bilirubin and transaminase values.
  • While the study was randomized, the cycled group did have more frequent late-onset sepsis 22 (65%) compared with 14 (39%) which reached statistical significance.
  • In addition, a trend towards more frequent non-surgical NEC in cyclical group was noted as well: 6 (18%) compared with 3 (8%).
  • PNAC was associated with days until full enteral nutrition/duration of parenteral nutrition and bronchopulmonary dysplasia.

The higher incidence of late-onset sepsis could have occurred randomly and affected the results; alternatively, the higher rate could reflect an increased risk of sepsis due to doubling the frequency of central line access.

This study was  only powered to detect a 25% difference between the groups; the authors estimate that a study with 290 patients would be needed in each group to identify a reduction of 10% in the incidence of PNAC.  As such, this study leaves open the possibility that cycled parenteral nutrition may be helpful in a smaller percentage, particularly if efforts are made to eliminate central line infections.  More promising efforts to minimized PNAC are noted in previous blog entries:

PNAC, PNALD, and IFAC

Optimizing lipids to minimize cholestasis

More on PNAC

Four advances for intestinal failure

Electrons and Organic Food

Posted on by

I still remember the Heisenberg uncertainty principle (Heisenberg states the uncertainty principle – PBS) from high school physics –thanks Mr. Pryor!  What quantum physicists don’t realize is that it is a leap of faith for anyone to believe in electrons much less to be concerned about measuring factors like speed or position.  I’ve never seen an electron but I’ve been convinced that they exist.

With organic foods, many people believe a health benefit exists, but does it and can it be proven?  A recent review weighs in (Ann Intern Med 2012; 157: 348-66) –thanks to Seth Marcus for pointing out this article.

This review from Stanford has been reported in multiple outlets and the soundbite is that organic foods are not better than conventional foods.  For example, the New York Times reports that the researchers “concluded that fruits and vegetables labeled organic were, on average, no more nutritious than their conventional counterparts, which tend to be far less expensive. Nor were they any less likely to be contaminated by dangerous bacteria like E. Coli.” Ultimately, “the researchers also found no obvious health advantages to organic meats.”

This is a vast oversimplification of this review.  So what did the researchers find and what were the limitations?

First –some background:

  • In 2010, U.S. sales of organic foods had increased to $26.7 billion; in contrast, only $3.6 billion was spent in 1997.
  • There are a number of different standards for organic foods, including U.S. Department of Agriculture (USDA), European Economic Community (EEC), and international federation of organic agriculture movement (IFOAM).
  • Typically organic foods are grown without synthetic pesticides or fertilizers or routine use of antibiotics/growth hormone.
  • Consumers often purchase organic foods due to concerns about effects of farming practices on environment, human health, animal welfare or perceptions of better taste.
  • Inclusion criteria for the cited reference allowed for 17 human studies and 223 nutrient/contamination studies of the initial 5908 potential relevant articles.

Key findings:

  • Conventional foods had 30% higher risk for pesticide contamination.
  • Conventional chicken and pork were more likely to have bacteria resistant to 3 or more antibiotics (33% risk difference).
  • Both organic and conventional products had frequent contamination with bacteria like Salmonella and Campylobacter.  Organic produce had higher risk for contamination with E. coli; this may have been due to some organic farms which used manure for fertilization.
  • There was not evidence that the organic foods were more nutritious.
  • Organic foods had higher levels of total phenols and ω-3 fatty acids.

Limitations:

  • No long-term studies of health outcomes have been performed.  The study with the longest duration included in this analysis was 2 years; the shortest was two days.
  • Variation in organic practices. Produce studies may not have reflected real-world organic practices.
  • Overall sample sizes were small (in total 13,806 human participants in 14 unique populations).
  • Reporting/publication bias.
  • Adherence with organic diets was varied; only 5 of the human studies evaluated participants who consumed a predominantly organic diet.

So, when one looks at this review, there are measurable differences in exposure to pesticides and antibiotic-resistant bacteria, despite variation in organic practices.  Specific nutrients are largely the same.  Whether any of these changes have a long-term health benefit is not known and would require an expensive long-term study to sort out.

 

One approach towards organic foods has been recommended by the Environmental Working Group.  They recommend “buying only organic when purchasing foods that contain the highest concentrations of pesticides, otherwise known as ‘the dirty dozen‘: peaches, strawberries, nectarines, apples, spinach, celery, pears, sweet bell peppers, cherries, potatoes, lettuce, and imported grapes” (Am J Clin Nutr 2010; 9 (suppl): 1499S-1505S).  This reference which discusses foods and potential hormonal effects on puberty goes on to state, “the biggest environmental exposure…is the ready availability of energy-dense foods” which contribute to obesity.

Related link:

Why are we seeing so many more cases

What do you know about the “exposome”?

Effects of pegylated interferon on growth

Posted on by

Besides examining the effectiveness of pegylated interferon for hepatitis C virus (HCV) in children, the PEDS-C (Pediatric Study of Hepatitis C) trial data has been studied to determine the effects of pegylated interferon (PEG) on growth and body composition (Hepatology 2012; 56: 523-31).

In this study of 114 children who were treated with PEG along with ribavirin (RBV), anthropometric measurements, dual-energy X-ray absorptiometry, dietary intakes, and activity assessments were performed.  Of the initial 114 children (5-18 years), 107 received treatment for more than 24 weeks: 14 for 24 weeks, 82 for 48 weeks, and 11 for 72 weeks.

In the group treated for 48 weeks, 29 (33%) had more than a 0.5 unit decrement in height-for-age score (HAZ).  Based on figure 2 in the study, most of the HAZ decrement at 48 weeks and resolved at 144 weeks (time after treatment initiation).  In contrast, weight-for-age and BMI scores returned to baseline after stopping HCV therapy.  The authors note that while most growth parameters generally were “reversible with cessation of therapy…HAZ scores had not returned to baseline after 2 years of observation in many.”

Another observation from the study was that weight and height decreased in tandem.  In contrast to sequential change, this type of change indicates that other mechanisms besides poor intake are likely affecting linear growth.  These HAZ effects were noted in adolescents; there was no difference in HAZ scores in preadolescent patients.

The potential effects on growth may influence the timing of therapy.  At the same time, as new HCV treatments are studied in pediatric patients, the effects of interferon may become a moot point.

Related blog entries

Pediatric HCV Guidelines

Understanding IL28B

Increased ferritin predicts poor response in Hepatitis C

Unknown unknowns for Hepatitis C

n-3 Fatty Acids and Cardiovascular Outcomes

Posted on by

A recent study has cast doubt on the benefit of n-3 fatty acids for preventing cardiovascular complications in patients with type 2 diabetes (NEJM 2012; 367: 309-18).

While previous studies have indicated that persons who consume fish regularly or take supplements with n-3 fatty acids have a reduced risk of cardiovascular events, there are many potential confounding variables.  This “ORIGIN” study (Outcome Reduction with an Initial Glargine Intervention) which had 12,611 patients undergo randomization looked at a high risk group (type 2 diabetes patients) but did not find any change in cardiovascular events, including death over a median followup of 6.2 years.  The treatment group received 1 gram of n-3 fatty acids which did result in a lower triglyceride level (by 14.5 mg/dL).

How do the authors explain the results of this negative study in comparison to previous reports?

  • Two of the largest trials had recruited patients with recent myocardial infarction –these patients may have been more likely to benefit
  • In ORIGIN study, more concomitant cardioprotective therapies were being used which could have reduced the potential benefit of n-3 fatty acids
  • Other study populations may have had a lower dietary intake of n-3 and therefore benefitted more from supplementation

While the results of this study may reduce the enthusiasm for n-3 fatty acids, several additional large studies (ASCEND/NCT00135226, VITAL/NCT01169259) are underway which should give additional information on this topic, including in participants at lower risk for cardiovascular events. In addition, the authors conclude that while their findings do not show a reduction in cardiovascular events, they state that dietary recommendations of increased fish consumption should not change; increased fish consumption not only increases n-3 fatty acids but results in lower intakes of red meats which may be harmful.

Related posts:

TODAY is worrisome for a lot of tomorrows

Who needs aspirin?

Cardiovascular disease for the entire family

Treating diabetes with surgery

Fat soluble vitamin deficiency -sometimes the rule rather than the exception

Posted on by

While it is well-known that cholestasis predisposes individuals to develop fat-soluble vitamin (FSV) deficiencies, the exact frequency is not clear.

A recent prospective multi center study of infants with biliary atresia (BA) indicates that FSV deficiency is quite frequent –thanks to Kipp Ellsworth for forwarding this article (DOI: 10.1542/peds.2011-1423; http://pediatrics.aappublications.org/content/early/2012/08/08/peds.2011-1423).  “Infants with BA are at risk for malabsorption of dietary lipid and fat-soluble vitamins (FSVs) due to insufficient intraluminal bile acid concentrations.”

To determine the frequency of FSV deficiencies, this study examined 92 infants with BA who were enrolled in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after hepatoportoenterostomy (HPE).  This study was conducted by the Biliary Atresia Research Consortium (BARC) between 2005-2008.

All infants were treated with a standardized dose of a liquid multiple FSV/d-α tocopheryl polyethylene glycol-1000 succinate (TPGS; a micelle forming water-soluble form of vitamin E).  Infants received initially ADEKs; later in the study, ∼32 months after start, participants were changed to AquADEKs due to a manufacturer’s change.  In addition, all infants received supplemental vitamin K, initially 2.5 mg three times per week.  As noted in supplement to article, the two study multivitamins have particularly low amounts of vitamin D (800 units) and vitamin E (80-100 units) compared to frequent dosing in clinical practice for severe cholestasis (see below).

TABLE 1 from study: Target FSV Levels and Replacement Regimens

  • Vitamin A (retinol)

Target:  19–77 mg/dL retinol:RBP molar ratio >0.8

Supplement strategy:  Increments of 5000 IU (up to 25–50 000 IU/d) orally or monthly intramuscular administration of 50 000 IU

  • D (25-hydroxy vitamin D)

Target: 15–45 ng/mL

Supplement: Increments of 1200 to 8000 IU orally daily of cholecalciferol or ergocalciferol; alternatively calcitriol at 0.05 to 0.20 mg/kg per day

  • E (α tocopherol) 

Target: 3.8–20.3 mg/mL & vitamin E:total serum lipids ratio >0.6 mg/g

Supplement: Increments of 25 IU/kg of TPGS orally daily (to 100 IU/kg per d)

  • K (phytonadione)

Target: INR ≤1.2

Supplementation Strategy:

  • <1.2-1.5  INR:  2.5 mg vitamin K orally daily
  • 1.5-1.8  INR: 1.8  2.0–5.0 mg vitamin K intramuscular and 2.5 mg vitamin K orally daily
  • >1.8 INR:  2.0–5.0 mg vitamin K intramuscular and 5.0 mg vitamin K orally daily

Results: FSV was common in infants with total bilirubin (TB) ≥2 mg/dL. At three months post HPE, only 3 infants with this degree of cholestasis were sufficient for all four vitamins.; at 6 months post HPE, all 24 infants with TB ≥2 mg/dL had at least one FSV deficiency: “100%, 79%, 50%, and 46%, respectively, for vitamins A, D, E, and K .”   Also, the incidence of vitamin D deficiency would be higher if the authors had chosen a higher target.

Take-home points:

  • FSV deficiencies are common particularly in patients with TB > 2mg/dL; thus careful monitoring is worthwhile
  • There is no current multivitamin that is adequate.  A better strategy is to individualize the dosing for each vitamin and consider injection (except for vitamin E) if needed

Initial individualized dosing of FSV supplementation in clinical practice for severe cholestasis (prior to deficiencies):

Vitamin A: start with ~5000 units daily.

Vitamin D: See previous posts for more information on dosing.  Two options include: Drisdol® (8000 IU/ml) 0.125ml/kg/day (=1000 IU/kg/day) and Bio-D-Mulsion Forte® http://www.bioticsresearch.com/node/1570 -each drop = 2,000 IU (also inexpensive)

Vitamin E (Liqui-E®/Nutr-E sol®26.6 IU/ml) 1ml/kg/day
with tocopherol polyethylene glycol succinate.  Alternative is AquaE®(Yasoo -www.yasooproducts.com/aqua-e/).

Vitamin K (phytonadione) 2.5mg QOD

Related posts:

Diagnosing biliary atresia earlier

Common to be “D-ficient”

Outcomes of Biliary Atresia

MicroRNAs and biliary atresia

Bleeding due to vitamin K deficiency

Optimizing lipids to minimize cholestasis

Posted on by

As discussed in previous blog entries (PNAC, PNALD, and IFAC, More on PNAC, Four advances for intestinal failure), the right amount of lipid and the type of lipid both can contribute to parenteral nutrition associated cholestasis (PNAC).  More information about SMOFlipid which is a complex mixed-type lipid emulsion derived from soybean, coconut, olive, and fish oils is available (JPGN 2012; 54: 797-802).  SMOF contains 30% soybean oil, 30% MCT, 25% monounsaturated fatty acids, and 15% fish oil.

This study had a retrospective cohort comparison design & examined serum bilirubin over 6 months in children with PN-associated cholestasis (PNAC).  In one cohort, 8 patients received the SMOFlipid and the other 9 patients continued on Intralipid (IL).

The SMOF cohort was receiving 81% of caloric needs as PN at entry whereas the IL cohort was receiving 92%.  Six months later, SMOF cohort was receiving 68% of caloric needs as PN compared with 50% for IL cohort.  Nevertheless, the SMOF group had improved cholestasis with a median bilirubin drop of 99 μmol/L compared with an increase of 79 μmol/L among IL patients.  Overall, 5 of 8 children in the SMOF group had resolution of jaundice compared with 2 of 9 in the IL group.

While the authors state that SMOF may have important properties to prevent PNALD, the study has limited ability to draw any firm conclusions.

The authors state that no other treatment innovations were introduced; however, the authors overlook the large discrepancy in lipid volume administered.  The IL group was receiving much more lipid both before and during study.  Prior to entry of study, the IL group was receiving about 3.1 g/kg/day whereas the SMOF group about 2 g/kg/day; the SMOF group continued initially at the same lipid dosing with the new formulation.  This is one of the problems with historical controls.  While the authors might believe that the cholestasis improved because of the lipid content, the key factor may in fact be the amount of lipid given.

In the same issue (JPGN 2012; 54: 803-11), specific plant sterols (PS) were elevated among neonates with intestinal failure-associated liver disease (IFALD).  This study looked at 28 neonates and 11 children from Finland who required PN for more than 28 days.  Specific markedly-elevated PS included stigmasterol, sitosterol, avenasterol and campesterol (Table 4 in study).  Some of these PS in the neonates were more than 20-fold higher than healthy controls.

Keep it cool

Posted on by

Now, what cooler than being cool?
Ice cold!
I can’t hear ya! I say what’s, what’s cooler than being cool?
Ice cold!
Alright alright alright alright alright alright alright alright alright alright alright alright alright alright alright alright!

Lyrics for “Hey Ya!” by Outkast

Keeping it cold is also the advice if you want to keep the bactericidal activity of breastmilk intake (JPGN 2012; 55: 146-49).  This study examined the effects of freezing from 48 healthy donors who provided samples of fresh breastmilk.  Bactericidal activity was determined by thawing breastmilk (in duplicate) and innoculating with bacterial strains and then comparing growth in breastmilk compared with control samples.

Freezing at -20 degrees celsius (C) for 1 month did not effect the bactericidal activity of breastmilk against either E coli or P aeruginosa.  In contrast, when samples were stored for three months, freezing at -80 degrees C was protective of this activity whereas -20 degrees C was not.

So if you are storing breastmilk for longer than 1 month, keep it cold if you can.

Related blog entry:

Long-chain polyunsaturated fatty acids, breastmilk, and infant cognition

Cholesterol controversy

Posted on by

Recent guidelines (Pediatrics 2012; 130: 353-56) have recommended universal screening for hypercholesterolemia between ages 9-11 along with additional targeted screening.  These recommendations have been met with a number of criticisms (Pediatrics 2012; 130: 349-52).

In the first referenced commentary, the experts who issued the guidelines commissioned by the National Heart Lung and Blood Institute (NHBLI) claim that the criticism “misrepresent the evidence regarding screening and the specificity and rigor of the guideline development.”  In the second commentary, the guidelines are considered overly aggressive and not adequately founded on evidence-based medicine.  In addition, they cite two JAMA commentaries that also question the wisdom of the guidelines (JAMA 2012; 307: 257-58, & 259-60).

NHBLI recommendations:

▪  Universal screening of all 9-11 year-olds with a nonfasting lipid panel.

▪  Targeted screening of 2-8 year-olds and 12-16 year-olds with 2 fasting lipid profiles.  The targeted group are for those with diabetes, hypertension, BMI >95%, smoke cigarettes, have a parent with cholesterol >240 (or known dyslipidemia), 1st or 2nd degree relative (includes parents, aunts, uncles, and grandparents) with stroke or coronary artery disease <55 years for men or <65 for women.  According to the critical commentary, 30-40% of children will meet family history criteria and many more will meet other criteria.

▪  If LDL ≥130 mg/dL, then a “CHILD-1” diet is recommended.

▪  Individuals with abnormal screening are to have fasting lipid panels every 6-12 months indefinitely even if their values become acceptable.

Criticisms and responses by guideline authors in italics

▪  While the critics concede that cumulative exposure to high LDL and hypertension increase the risk of cardiovascular disease (CVD), they indicate that with the exception of a small number of individuals (rare homozygous familial hypercholesterolemia) that there is not proof that intervention in childhood is necessary.  The chain of evidence cited by the panel has “notably the absence of even observational evidence or modeling to estimate the clinical event benefits of screening for and intervening on these risk factors in children.”  Atherosclerosis is a lifelong process…Heterozygous familial hypercholesterolemia affects 1:500 and 51% of untreated men develop CV disease events by age 50 years… Accidental death studies (ages 15-30 years) have shown that a 30 mg/dL increase in non-HDL was equivalent to 2 years of vascular aging.  Bogalusa Heart Study showed that number of risk factors correlated with increased atherosclerosis at autopsy after accidental death.  Carotid intima media thickness in adulthood correlates with LDL levels obtained between 12-18 years of age.

▪  No quantification of potential harms such as neuroses, family conflict, CVD anxiety or from medication.  Among children with familial cardiovascular disease, interview studies have shown positive future health perceptions and effective coping.  ‘A study of universal CV risk screening in schools, accompanied by environmental change, showed improvements in healthy lifestyle behaviors and CV risk profiles.’  Risk of statin therapy, (only 0.8% of adolescents would be eligible per authors) has shown no adverse effects in children and adolescents.

▪ The majority of the panel members…disclosed an extensive assortment of financial relationships with companies making lipid-lowering drugs and lipid-testing instruments.  Evidence regarding the efficacy and safety of these medications would not be available without academic partnership with industry.  Potential conflicts of interest were declared and vetted.

▪  Cost/cost-effectiveness. The present policy proposes an intervention applied to a healthy and asymptomatic population, with an enormous impact on costs and the potential to transform well children into patients with a chronic disease label. “Any intervention with nonzero benefit may be recommended, regardless of how much it costs and how much better health might be achieved by investing those resources elsewhere.”  There have been several studies exploring the cost-effectiveness of screening and management strategies for familial hypercholesterolemia (FH). In the Netherlands, a genetic screening program showed that new cases of FH gained 3.3 years of life at an average lifetime cost of US$8700 per year gained.  More complex cost-effectiveness modeling of treatment of children and adolescents has not yet been performed.

So who is right in this debate?

Previous related blog entry:

Cardiovascular disease for the entire family