This month, for the sake of sheer time-saving and convenience, I wanted to pull a bit from my current capstone research project for my final semester as a graduate student in nutrition & human performance. My research topic is covering non-alcoholic fatty liver disease (NAFLD) in pediatrics and whether a nutrition intervention of (broadly) a higher carbohydrate or more mediterranean type diet would benefit the specific measurable outcomes of fasting insulin and glucose.
To start, I’ve learned an immense amount of knowledge from my time in graduate school. I think specifically, regarding any chronic disease, that no one THING causes deleterious effects from a metabolic standpoint. It’s a cascade of factors from lifestyle, genetics, environment, and whatever else you’d like to throw in there. Negative effects on our health come from so many places.
There is currently no FDA-approved medication for non-alcoholic fatty liver disease (NAFLD), which affects a significant percentage of both adults and children worldwide and places a significant health and economic burden on all civilizations. The rapid increase in levels of sedentary behavior, low levels of physical exercise, excess calorie intake relative to expenditure, and nutritionally unbalanced diets have all contributed to the increasing prevalence of this condition.
NAFLD Pathophysiology
Why is NAFLD becoming a pandemic worldwide? There is no single solution. Modernization of societies in general is associated with an increase in the prevalence of NAFLD because we consume more calories than we burn. Food is just easier to get. Patients with NAFLD who are obese have been shown to consume more calories than healthy, lean people, and some studies have linked this to an increase in sugar consumption. Fructose in particular can trigger the lipogenesis processes that worsen NAFLD. Sugars. Since the liver is the only organ that can effectively break down fructose, any consumed sugar is sent there where it is primarily converted to triglycerides through a process called de novo lipogenesis. It would also be anticipated that the onset of hepatic insulin resistance, in which insulin activation of glycogen synthase is compromised, moves glucose into lipogenic pathways and further advances NAFLD.
Relationship between NAFLD and Insulin Resistance
A big theme within The Daily Greens here continues to be around your metabolic health. Being insulin sensitive is one of the best possible ways to prevent the majority of chronic diseases. Being insulin resistant, leading to complications down the road such as NAFLD can certainly be mitigated in children and the global population burdened by this overall.
Blood Sugar (Glucose) Levels
A trend seeming to take the health and wellness social media scene by storm is the use of continuous glucose monitors (CGM) to measure daily trends in your glucose level. There’s a handful of companies out there that the public is now able to regularly purchase (rent/subscribe) to these products that you can place on the back of your arm and begin seeing your daily fluctuations. Overall, I just don’t see the utility of this. It does at best- nothing really?? It tells you your blood sugar is going up after eating a piece of fruit. Observing that 1-2 hours later, it returned to normal. This is 100% NORMAL human physiology. Therefore, at worst, these products can lead someone to develop a sort of orthorexia around food choices.
But… What IF you do see some abnormal fluctuations, yet your yearly checkup reveals normal fasting blood glucose and A1C? I do think there’s some validity here. And this is where my research is sort of geared towards. Along with early detection of glucose abnormalities, body fat and muscle mass are probably even bigger factors to look toward. A 2016 clinical trial looked at, admittedly, not “healthy” children but those diagnosed with NAFLD who were also classified as obese. The study looked at correlations and differences between using a CGM and the standard oral glucose tolerance test (OGTT) to predict severity and progression of liver fibrosis. It concluded that the use of CGM demonstrated a higher specificity in detecting abnormal glucose fluctuations than the isolated OGGT. Obviously, these children in the trial WERE obese and WERE diagnosed with NAFLD. It does raise the question as to whether this has utility in the general population.
Lean Muscle Mass
Let’s switch to looking at body composition. I stated earlier that a factor that’s certainly easier to identify in individuals is the fat to muscle ratio. Body mass index (BMI) is the most commonly used method to assess overweightness and obesity, which are characterized by excessive accumulation of fat. However, BMI has several limitations in assessing obesity‐related cardiometabolic risks because it cannot distinguish between fat and muscle mass. For instance, normal-weight obesity is linked to metabolic syndrome (MetS) and insulin resistance (IR), and metabolically obese normal-weight people have higher cardiovascular risks than metabolically unhealthy obese people.
The fat:muscle ratio (FMR), metabolic syndrome (MetS) and insulin resistance (IR) were examined in a 2020 cross-sectional study in South Korea. It is significant to note that this is the first to examine the relationships between MetS and IR and FMR, as measured by dual-energy X-ray absorptiometry (DXA), and to establish sex-specific optimal cut-off values of the FMR for doing so in the Korean population. The study discovered that waist circumference, BMI, and HOMA-IR (a test of insulin resistance) gradually increased as the FMR increased as well. It also discovered that comorbidity prevalence, the prevalence of MetS, and the percentage of participants satisfying each MetS criterion tended to gradually increase.
Summary
NAFLD, an outcome that’s becoming more and more prevalent in children now, is a debilitating condition with broad metabolic consequences. Regarding my actual research question regarding nutritional intervention, a caloric deficit (losing weight) seems to be what really drives down the excess accumulated liver fat along with improving your metabolic parameters across the board. Which diet is BETTER?? To my surprise, the Mediterranean diet actually looks to do pretty well when compared to a higher carb diet. This could come down to an increased level of triglycerides being synthesized when carbohydrates are too high?? A lot of the underlying mechanisms are still unclear. The lack of physical activity is what I think is driving this condition at its roots. Sedentary behavior from kids, along with global nutrition, is pretty subpar. We face significant challenges in tackling the growing and global epidemic of NAFLD. The widespread prevalence of NAFLD, the attendant risks of metabolic and hepatic complications, and the lack of approved therapies are significant hurdles. But, there is a solid and mechanistic foundation with which to tackle this challenge. Challenges remain in developing better tools to predict who is at risk for NAFLD (especially in non-obese individuals), non-invasively diagnosing NAFLD, and stratifying those patients at risk for progression. Changes in health policies are needed to decrease the incidence of NAFLD and regulatory agencies may need to consider NAFLD per se as a treatment indication.