One in five people with type 2 diabetes will develop metabolic dysfunction-associated fatty liver disease (MAFLD), which has a high mortality rate and is one of the primary indications for liver transplant. In the longest study of its kind, published in Diabetes, Obesity and Metabolism, NewYork-Presbyterian and Weill Cornell Medicine physicians showed that weight loss can play a significant and long-lasting role in reducing the burden of MAFLD in people with diabetes and obesity. Below, Sangeeta Kashyap, MD, an endocrinologist at NewYork-Presbyterian and Weill Cornell Medicine, explains how weight loss affects MAFLD and the need for diagnostic testing to catch it at reversible stages.
Research Background
MAFLD is significant for people with diabetes who are overweight and it's completely under recognized. Liver cirrhosis in people with metabolic disease is a silent killer. It contributes to heart disease because the inflammation and fat in the liver also affects our arteries and blood vessels. It also makes diabetes even harder to control. But a lot of clinicians don't pay attention to liver disease because the liver tests that we measure through a blood panel usually look fine. Liver failure doesn’t present until very late.
The ARMMS-T2D (Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes) trial previously looked at how effective bariatric surgery is compared to the best medical/lifestyle therapy for diabetes. Through that study, we found that with surgery, patients can achieve greater weight loss, and the effect was durable over 12 years. We also found that 25% of people had complete remission of their diabetes. This led us to wonder about the impact these treatments could have on liver disease.
In our recent study ancillary to ARMMS-T2D, we explored just that. Study participants received either bariatric surgery or medical/lifestyle interventions, including the newer GLP agonist drugs. We followed people for up to 12 years after they received these treatments and calculated their hepatic steatosis or liver fibrosis scores at baseline and within 7-10 years of follow up.
Study Results
Our study included 209 of the patients originally enrolled in the ARMMS-T2D study. Of those, 78 were assigned to the medical/lifestyle group and 131 in the surgery group. At baseline, we saw no differences in steatosis or fibrosis scores between the two groups.
At follow-up, we saw the prevalence of liver steatosis decreased to 85.9% and advanced liver fibrosis remained comparatively low. This means that regardless of whether you’re treating diabetes with surgery or medication/lifestyle changes, both interventions prevent the accumulation of liver fat.
We looked at people who underwent gastric bypass, sleeve gastrectomy, and gastric band, and it didn't matter which type of surgery the patient received. The surgical group had a greater improvement in steatosis scores than the medical/lifestyle intervention group, but medical therapy takes a much longer time to see a benefit than surgery.
We didn't see changes in fibrosis, but we think it's because we didn't follow people long enough or because we didn't have enough patients with fibrosis at baseline entry in our sample size. However, we believe that both interventions can be equally helpful for fibrosis.
The Need for Enhanced Screening
Both surgery and medical/lifestyle interventions are very effective in treating diabetes; however, a lot of people still are not getting these treatments. The results from our study suggest that weight loss is very important in the early stages of MAFLD. If we can pick up liver disease early, we can initiate weight loss either through surgery or with medical therapy and prevent liver fibrosis.
The liver is a very resilient organ, unlike other organs in our body. If you can catch and treat the disease, it will completely normalize. Liver disease goes through four stages—F1, F2, F3, and F4. Up until F2, it's completely preventable and you can cause regression. The liver scores are easy to calculate, like cardiovascular risk scores, and they can be part of the assessment.
At NewYork-Presbyterian and Weill Cornell Medicine, we take an integrated holistic care approach to managing these patients where our specialists work together to help people with diabetes, metabolic dysfunction, and liver disease live longer. I encourage other clinicians to perform non-invasive testing for metabolic dysfunction and liver disease in every patient with type 2 diabetes, obesity, and metabolic syndrome. MAFLD can be caught early if you apply non-invasive testing, and if they're abnormal, refer patients to endocrinology and hepatology.
