Is Cognition Affected by Obesity/Metabolic Disease?

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A recent provocative study : “Childhood Metabolic Biomarkers Are Associated with Performance on Cognitive Tasks in Young Children” ALB Shapiro et al. J Pediatr 2019; 211: 92-7

Methods: Data were obtained from children (n=137, 4.6 years old on average) participating in the Healthy Start study, a pre-birth cohort in Colorado. This included metabolic markers (HOMA-IR, glucose, insulin) and cognitive performance markers (Flanker task, Dimensional Change Card Sort test (which assesses cognitive flexibility), and Picture Vocabulary test).

Key findings:

  • HOMA-IR, glucose, and insulin were all inversely significantly-associated with cognitive flexibility testing. Thus, the authors found that “greater blood biomarkers of poor metabolic health are related to lower cognitive flexibility and inhibitory control in healthy, young children.”

Discussion:

  • The authors note that their findings “contribute to the large body of literature in children with overt type 1 and type 2 diabetes that demonstrates consistent and negative effects of poor metabolic health on cognition.”
  • The metabolic effects on cognition may be more critical in childhood due to brain maturation as well as potential for longer exposure periods.  However, studies from adults indicate that “adults without overt diabetes, the cumulative burden of metabolic conditions (eg. obesity, hyperglycemia) was significantly associated with lower cognitive scores.”

My take: While the effects of metabolic disease on cardiovascular disease is well-recognized, this study adds to the body of knowledge that indicates the potential harm of metabolic disease on the brain as well.

Near Chattahoochee River

An Insurance Company Doing the Right Thing (with Calprotectin)

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“An Insurance Company Doing the Right Thing” –not The Onion headline this time.

Recently (April 7. 2019) United Healthcare put out a policy statement explicitly stating:

“Fecal measurement of calprotectin is proven and medically necessary for establishing the diagnosis or for management of the following:

  • Crohn’s Disease
  • Ulcerative Colitis”

Thanks to Kim Conn for identifying this policy.

The policy statement provides an in-depth rationale for why calprotectin is medically-indicated along with supporting recommendations from multiple GI societies and National Institute for Health and Care Excellence (NICE).  The policy statement includes a long list of references and would provide a strong argument in supporting calprotectin testing for all insurance providers.

Here’s the link: FECAL CALPROTECTIN TESTING United Healthcare.

Related blog posts:

Lots of lazy river floating. Deschutes River, Bend OR

Declining and Aging Rural Physician Workforce

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A recent article (L Skinner et al NEJM 2019; 381: 299-301) provided data regarding the worsening disparity in physician availability in rural areas.

Key points:

  • “While the total number of rural physicians grew only 3% (from about 61,000 in 2000 to 62,700 in 2017), the number of physicians under age 50 years living in rural areas decreased by 25%.”
  • “By 2017, more than half of rural physicians were at least 50 years old, and more than a quarter were at least 60.” In urban areas, the numbers were 39% and 18% respectively.
  • It is projected that instead of the current 12 physicians per 10,000 population in 2017 there will be a drop of 23% (9.4 per 10,000) in 2030 in rural areas; in contrast, nonrural physicians supply will be essentially the same in 2030 (29.6 per 10,000) as current supply (30.7).
  • The fact that there will be one-third fewer physicians is coupled with the fact that rural areas have populations that are older, poorer, worse health, lower life expectancy, and less insurance coverage

My take: This report highlights the current disparity in rural health care and how this is worsening as the rural physician population ages.

Related blog posts:

Risk Factors for Progressive, Fibrotic Fatty Liver Disease

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Briefly noted: A recent study (A Mosca et al. J Pediatr 2019; 211: 72-7) examined 182 obese/overweight children with nonalcoholic fatty liver disease (NAFLD). 137 (75.3%) had liver fibrosis. 39 had fibrosis level ≥2 (21.4%)

Risk factors for liver fibrosis:

  • Not being breastfed OR 3.1
  • Parenteral obesity OR 2.9
  • PNPLA3 (palatin like phospholipase domain-containing 3) GG (1148M) variant OR 2.1
  • Fructose consumption (OR 1.6 per 1 g/day increase)
  • Vitamin D deficiency (25-OH <20 mg/dL) OR 1.24
  • A high socioeconomic status was inversely associated with fibrosis OR 0.3

Related blog posts:

 

SMOF Neurodevelopmental Data Looks Good –In Five Years We’ll Know More

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A recent study (C Binder et al. J Pediatr 2019; 211: 46-53) examined electrophysiological brain maturation in a randomized double-blinded controlled trial of SMOF lipid compared to soybean lipid emulsion for extremely low birth weight (ELBW) premature infants. This was a prespecified secondary outcome analysis of a randomized trial of 230 infants (2012-2015).

It is recognized that the ELBW infants have very little nutritional reserve.  In addition, DHA which is transferred to the fetus in high amounts in the last trimester is absent from parenteral soybean lipid emulsions.  Thus, the authors explored whether SMOF lipid which is a mixture of lipids (30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and  15% fish oil) and contains DHA would have a favorable effect on neurocognitive outcomes.

In this study, the authors examined amplitude-integrated electroencephalography measurements (aEEG)  to assess neurodevelopment. Both groups received similar lipid dosing, SMOF 2.2 g/day and Soybean 2.1 g/day.

Key findings:

  • Among the available 121 infants in the subgroup with aEEG (n=63 SMOF, n=58 soybean), maximum maturational scores on aEEG were achieved 2 weeks earlier in the SMOF group (36.4 weeks vs 38.4 weeks, P<.001).

Limitation:

  • aEEG is a marker of neurocognitive development; however, more adequate outcomes of  neurodevelopmental progress are needed. The authors plan to follow these infants up to 5 years of age.

My take: This study is very favorable for the use of SMOF lipids in premature infants.  — SMOF lipid emulsion by itself may improve neurocognitive outcomes. In addition, clinicians are more likely to provide adequate amounts of lipid calories with SMOF as compared to soybean emulsion which is often restricted to minimize liver injury.  Giving adequate lipid calories is also likely to enhance neurological outcomes.

Related blog posts:

Incredibly blue waters of Crater Lake, Oregon -from Wizard Island

 

Sclerosing Cholangitis-Like Changes Due to Drug Induced Liver Injury

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A recent study (J Ahmad et al. Clin Gastroenterol Hepatol 2019; 17: 789-90) reviewed subjects in enrolled in drug-induced liver injury (DILI) prospective cohort to determine the frequency of sclerosing cholangitis (SC)-like changes in this population.  SC-like changes have previously been noted in up to 10% of DILI cases (Dig Liv dis 2015; 47: 502-7). In this study, 233 of 1487 subjects had underwent an MRI.

Key findings:

  • Four of 56 (7%) with adequate quality images had SC-like images (4 with intrahepatic stricture and 1 with a common hepatic duct stricture as well)
  • Patients with SC-like changes had a more severe initial injury noted and were more likely to develop chronic injury as noted by persistent lab abnormalities at 6 months

My take: This study indicates that a severe DILI can result in secondary sclerosing cholangitis.

Related blog posts:

 

Dust Mites and Eosinophilic Esophagitis

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Given seasonal fluctuation in the activity of eosinophilic esophagitis (EoE), aeroallergens have been considered a trigger in some patients.

Briefly noted: A recent study (A Ravi et al. Gastroenterol 2019; 157: 255-6, editorial 17) showed that dust mite antigen was present in esophageal biopsy specimens at a greater level in adult patients with EoE compared to controls.  With active EoE, patients had dust mite staining in 1.6% of the field which was significantly greater than patients with inactive EoE (0.7). The control group had a complete absence of epithelial dust mite staining.

The editorial (Seena Aceves) notes that these investigators have also shown gluten accumulation in the EoE esophagus.  Whether dust mite antigens or other specific postulated aeroallergens plays a causative role is unclear.  This study shows the presence of these antigens in the esophagus but does not show whether this is an epiphenomenon due to increased permeability or whether these antigens activate the local immune system.

A second study (T Patton et al. JPGN 2019; 69: e43-e48) describes the outcome of coexisting celiac disease and eosinophilic esophagitis in 22 children (from a cohort of 350 children with celiac disease. 17 had repeat biopsies.  Four of 17 (23.5%) had resolution of EoE with a gluten-free diet.  Related blog post: Is there a Link Between Eosinophilic Esophagitis and Celiac Disease?

Sagrada Familia, Barcelona

“Tofacitinib: A Jak of All Trades”

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The clever title is derived from an editorial (KE Burke, AN Ananthakrishan. Clin Gastroenterol Hepatol 2019; 17: 1438-40) regarding three recent publications regarding Tofacitinib, a non-selective inhibitor of janus kinase (JAK) enzymes 1,2 and 3 which was FDA-approved in May 2018 for moderate to severe ulcerative colitis. This report was published prior to recent FDA warning regarding blood clots: FDA Warning on Tofacitinib

Two of the reports have been summarized previously on this blog:

The third study examines the safety of tofacitinib: W Sandborn et al. Clin Gastroenterol Hepatol 2019; 17: 1541-50

Methods: This study analyzed data from phase 2 and phase 3 trials with 1157 patients who had a median treatment of 1.4 years (1613 person-years).  More than three-fourths were receiving 10 mg BID.

Findings:

  • Serious infections were infrequent but there was a dose response relationship associated with herpes zoster infections.  At 10 mg BID,  the frequency was 5% whereas the rate was 1.5% in those receiving 5 mg BID and 0.5% in placebo-treated patients. This is likely related to interference of interferon production related to JAK inhibitor disruption.
  • Sandborn et al conclude that the “safety profile of tofacitinib for patients with UC appeared similar to that reported for patients with rheumatoid arthritis and for patients with UC treated with biologic agents, except for the higher incidence rate of herpes zoster infection.”

The editorial recommends NOT using tofacitinib for acute severe ulcerative colitis (ASUC); it “should be encouraged only in selected patients and preferably in the context of a research study.”  “Infliximab and cyclosporine [should be used] for steroid refractory UC;” however, they suggest that “one can consider initiating tofacitinib PRIOR to patients becoming steroid refractory.  “It could be used upfront on day 1.”

Related blog posts -Tofacitinib:

Related blog posts -ASUC:

Ciutedella Park, Barcelona

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.