Fatty Liver Disease (MASLD) & Insulin Resistance
Prevalence trajectories in the USA and United Kingdom, 1975–2022. Metabolic dysfunction-associated steatotic liver disease (MASLD — formerly NAFLD) is now the most common liver condition in the Western world, affecting an estimated one in three adults. The evidence is unambiguous: insulin resistance is both the primary driver and the central perpetuating mechanism. Without insulin resistance, MASLD does not develop. The correlation between the two prevalence curves over five decades is among the strongest in this entire series.
USA — Insulin Resistance vs MASLD (Fatty Liver)
1975 – 2022 | % of adults | Insulin Resistance % (left axis) · MASLD % (right axis)
UK — Insulin Resistance vs MASLD (Fatty Liver)
1975 – 2022 | % of adults | Insulin Resistance % (left axis) · MASLD % (right axis)
Why the two curves don't track each other exactly — even when the correlation is very high:
The solid line shows the percentage of adults with insulin resistance across the entire population — everyone with measurable insulin resistance, regardless of what condition it causes them. Because insulin resistance is the upstream root cause of many different diseases — type 2 diabetes, hypertension, cognitive decline, cardiovascular disease and more — this curve rises gradually as the burden is shared across all of those outcomes.
The dotted line shows the prevalence of MASLD specifically — only the people for whom insulin resistance has expressed itself as fatty liver disease. This curve can rise more steeply because it captures decades of accumulated cases: someone may develop insulin resistance at 35 but not be diagnosed with MASLD until their 50s, so even a modest early rise in IR translates into a much larger rise in diagnosed cases years later.
The r value (e.g. r = 0.96) is a correlation coefficient. It doesn't measure whether the two lines are the same height — it measures how consistently they move together over time. An r of 0.96 means that 96% of the rise in MASLD over the past five decades is statistically explained by the parallel rise in insulin resistance.
What the r value tells you:
0.50–0.70 — Modest connection. The two trends are related but other factors are involved.
0.70–0.90 — Strong connection. Insulin resistance is a major driver, alongside other causes.
0.90 and above — Dominant connection. Insulin resistance accounts for the overwhelming
majority of the trend. At this level, it is difficult to argue that other factors are primarily responsible.
The values seen here — r = 0.94 to 0.96 — place insulin resistance firmly in this category.
Why the USA and UK figures differ: The USA figure (~38%) reflects broader diagnostic uptake and a higher baseline obesity/metabolic syndrome prevalence, driven partly by an ultra-processed food supply that is more extreme than the UK's. The UK figure (~29%) reflects the same underlying trend but at a lower absolute level, consistent with marginally lower rates of severe obesity and metabolic syndrome in England. Both populations show the same directional trajectory: rising in close parallel with insulin resistance over 50 years. Neither represents a healthy baseline — both are far above any pre-industrial norm.
The Mechanistic Pathway: How IR Causes Fatty Liver
The pathway from insulin resistance to MASLD is one of the most thoroughly documented in metabolic medicine:
- Insulin resistance in adipose tissue → unrestrained lipolysis → excess free fatty acids (FFAs) flood the portal circulation to the liver.
- Liver receives excess FFAs → overwhelmed mitochondrial beta-oxidation → FFAs converted to triglycerides → triglycerides accumulate in hepatocytes → hepatic steatosis (fatty liver).
- Compensatory hyperinsulinaemia → stimulates de novo lipogenesis (DNL) in the liver via SREBP-1c → accelerates fat synthesis within liver cells directly.
- Gut dysbiosis → leaky gut → LPS translocation → portal vein LPS reaches liver → activates Kupffer cells → hepatic inflammation → progression from simple steatosis to steatohepatitis (MASH).
- Chronic hepatic inflammation + ongoing IR → stellate cell activation → fibrosis → cirrhosis in a significant minority.
This is not a coincidental association. Reversing insulin resistance — through very low-carbohydrate diet, intermittent fasting, and gut restoration — consistently reduces hepatic fat, often dramatically, and in some cases achieves complete histological resolution. Sources: Marchesini et al. (2001); Bugianesi et al. (2005); Tilg & Moschen (2010); Younossi et al. (2023); Cusi et al. (2022 ADA guidelines).
Data Sources & Citations
```MASLD / NAFLD USA — prevalence trend:
Younossi ZM et al. Global epidemiology of nonalcoholic fatty liver disease.
Hepatology 2016;64(1):73–84.
Younossi ZM et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes.
J Hepatol 2019;71(4):793–801.
Cusi K et al. AACE Clinical Practice Guideline for NAFLD. Endocr Pract 2022;28(5):528–562.
NCD Risk Factor Collaboration. Trends in adult body-mass index. Lancet 2016;387:1377–1396.
NHANES series 1988–2018. https://www.cdc.gov/nchs/nhanes/
MASLD / NAFLD UK — prevalence trend:
Sheridan DA et al. Non-alcoholic fatty liver disease in the UK.
Frontline Gastroenterol 2016;7(4):276–281.
Williams CD et al. Prevalence of nonalcoholic fatty liver disease utilizing ultrasound and liver biopsy.
Hepatology 2011;53(5):1634–1638.
Health Survey for England 2022. NHS Digital.
https://digital.nhs.uk/…/health-survey-for-england/2022-part-2
Public Health England. Non-alcoholic fatty liver disease: epidemiology and natural history. 2017.
Mechanistic evidence — IR causes MASLD:
Marchesini G et al. Insulin resistance in nonalcoholic steatohepatitis.
J Hepatol 2001;35(4):543–550.
Bugianesi E et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease.
J Hepatol 2005;43(1):156–164.
Tilg H & Moschen AR. Insulin resistance, inflammation, and non-alcoholic fatty liver disease.
Trends Endocrinol Metab 2008;19(10):371–379.
Samuel VT & Shulman GI. The pathogenesis of insulin resistance.
J Clin Invest 2016;126(1):12–22.
Targher G et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease.
Lancet Diabetes Endocrinol 2020;8(11):938–946.
MASLD reversal via dietary intervention:
Promrat K et al. Effects of weight loss on NAFLD. Hepatology 2010;51(1):121–129.
Browning JD et al. Short-term weight loss and hepatic triglyceride reduction.
Am J Clin Nutr 2011;93(5):1048–1052.
Tendler D et al. The effect of a low-carbohydrate, ketogenic diet on NAFLD.
Dig Dis Sci 2007;52(2):589–593.
Watanabe M et al. Beneficial effects of the ketogenic diet on NAFLD.
Nutrients 2020;12(7):2090.
Insulin Resistance USA & UK prevalence:
Hirode G & Wong RJ. Trends in the prevalence of metabolic syndrome in the United States.
JAMA 2020;323(24):2526–2528.
Diabetes UK. Diabetes statistics.
https://www.diabetesuk.org/…/statistics/
Frontiers in Endocrinology meta-analysis 2025.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11601873/