Wellness Check: Nutrition

2 Minute Medicine is pleased to announce that we are launching Wellness Check, a new series dedicated to exploring new research evidence focused on wellness. Each week, we will report on articles examining different aspects of wellness, including (but not limited to) nutrition, sleep, reproductive health, substance use and mental health. This week, we explore the latest evidence-based updates in nutrition. 

Obesity may be associated with better response to immune checkpoint blockade therapy

1. In this study, patients who were obese or overweight had better survival compared to normal weight patients after receiving immune checkpoint blockade treatment for their cancer.

2. In patients with high tumor mutation burden, obesity was associated with greater response rate difference.

Evidence Rating Level: 2 (Good)

In patients with cancer, a phenomenon called the “obesity paradox” has been described, where obesity was surprisingly associated with better treatment outcomes. However, it is unclear whether this association is observed across cancer types and cancer therapy modalities. In the advent of immune checkpoint blockade therapy, whether and to what degree this association is present in this context is not well understood.

This prospective cohort study included 1840 adult cancer patients (57.55% male) at Memorial Sloan Kettering Cancer Center who had received at least 1 dose of immune checkpoint blockade (ICB) treatment from 2014 through 2019. The body mass index (BMI) of patients were measured within 30 days before treatment. The primary outcomes measured were overall and progression-free survival after ICB treatment.

Compared to patients with normal weight, both obese and overweight patients had better overall survival and progression-free survival. This analysis was further stratified based on number of tumor mutations (TMB) present at time of treatment. In both patients with high (>10) and lower number of tumor mutations (<10), obesity was associated with better overall and progression-free survival. Interestingly, the response rate difference between obese and normal weight patients was larger in patients with >10 TMBs compared to those with TMB <10. This study was limited in only having BMI as a measure of obesity, which could falsely categorize someone with higher muscle mass as “obese”. Therefore, which molecular sequelae of obesity underpins this observed association remains unclear. Nonetheless, this study highlighted an association between obesity and outcomes post immunotherapy for diverse types of cancers and suggest further work to be done to better elucidate the underpinning mechanism of this observation.

Aberrant levels of B12 and folate may be associated with increased risk of cardiovascular death in patients with diabetes

1. In this study, both low and high levels of B12 in serum was associated with higher risk of cardiovascular disease death amongst patients with type 2 diabetes.

2. Low level of serum folate were also associated with higher risk of cardiovascular disease death in patients with type 2 diabetes.

Evidence Rating Level: 2 (Good)

Folate (vitamin B9) and cobalamin (vitamin B12) are essential vitamins that play important roles in nucleotide and amino acid biosynthesis. Deficiency in folate and B12 are associated with many hematologic and neurologic abnormalities. Furthermore, folate deficiency has been observed in patient with diabetes and was shown to be associated with increased risk of cardiovascular disease (CVD). However, studies assessing the association between serum folate levels and CVD-related mortality in patients with diabetes have reported conflicting results.

This prospective cohort study looked at 8067 adults with type 2 diabetes in the United States. 7700 of these patients (50.5% male) had available serum folate levels and 4860 of these participants (50.7% men) had available serum B12 levels. Patients who were pregnant or had cancer were excluded from analysis. The primary outcome measured was number of CVD-related deaths among patients with different levels of serum folate and B12, with concentrations in the 25^th percentile use as reference.

Results showed that for folate, hazard ratio for CVD mortality was significantly higher for patients in the lower quartile (1.43) even after adjusting for potential confounders such as age, sex, race, education, income, alcohol, and physical activity. For vitamin B12, the hazard ratio for CVD mortality was increased in participants in both the lowest quartile (1.74) and highest quartile (2.32). Similar patterns were identified in terms of all-cause mortality. Unfortunately, this study was limited as the chronic state of B12 and folate level in these patients were unclear as the serum levels were only measured once. Nevertheless, this study provided robust data that suggest aberrant levels of B12 and folate may be associated with higher risk of CVD-related mortality in patients with diabetes. Therefore, prospective studies that test whether careful therapeutic control of folate and vitamin B12 levels can modulate rates of CVD mortality in patients with diabetes would be of interest.

Enteric administration of recombinant human insulin to preterm infants is safe and effective

1. In this study, enteric administration of recombinant human insulin was safe in preterm infants.

2. Insulin supplementation of human milk or formula given to preterm infants reduced time to achieve full enteric feeding in these patients.

Evidence Rating Level: 1 (Excellent)

Feeding intolerance due to immature gastrointestinal track development is prevalent among premature infants and causes significant morbidity and mortality. Preterm infants fed with mother’s own milk, which contains insulin, have been shown to promote intestinal maturation and decrease symptoms of feeding intolerance. However, whether addition of recombinant human insulin (rh insulin) to enteral feeds for preterm infants is safe and effective in reducing feeding intolerance has not been rigorously tested.

This multi-country randomized-control trial tested the safety and efficacy of supplementing human milk or formula with rh insulin for preterm infants. 303 infants born between 26 and 32 weeks of gestational age were randomized to receive either placebo, low, or high dose rh insulin in a 1:1:1 ratio. Infants with congenital malformations, infection, and hyperinsulinemia were excluded. The primary outcome measured was time to achieve full enteral feeding (FEF) defined as enteral intake of at least 150mL/kg per day for 3 consecutive days. The study was stopped 28 days after start of intervention or whenever the primary end point was reached.

Infants receiving low (10 days) and high (10 days) dose rh insulin achieved FEF in a shorter amount of time compared to infants receiving placebo (14 days). There was no significant difference in rates of severe adverse events in interventional and placebo groups. Lastly, no infants in the interventional group developed insulin antibodies. Overall, this study provided robust results that support the use of rh insulin as a supplement in human milk or formula feeding of preterm infants. However, one limitation of this study was its small size and use of only two doses of insulin. Therefore, further prospective studies testing different concentrations of insulin and more long-term indicators of nutritional state and development would be necessary to help determine how to use rh insulin supplementation in the most clinically effective and relevant manner.

Image: PD

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