The 2023 ADA Guideline Has Three Major Updates, Recommending NAFLD Screening For All Patients With Type 2 Diabetes

Update 1: GLP-1RA and pioglitazone are the first choices for treatment, and NAFLD screening is recommended for all patients with type 2 diabetes and prediabetes

New ADA guidelines: NAFLD screening and fibrosis risk stratification are recommended for all adult patients with type 2 diabetes or prediabetes (especially those with obesity or cardiometabolic risk factors/established cardiovascular disease) -4 index), even if liver enzymes are normal. For adults with diabetes or prediabetes who have persistently elevated plasma transaminase levels for >6 months and a low FIB-4 index, other causes of liver disease should be evaluated.

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ADA pointed out that both diabetes and liver disease are common clinical chronic diseases, and up to 70% of patients with type 2 diabetes are affected by liver disease. Liver disease was also more common in prediabetic and obese patients with type 1 diabetes. NAFLD is the most common liver disease in people with diabetes and can lead to cirrhosis, liver cancer, and an increased risk of cardiovascular disease and death. In addition, nonalcoholic steatohepatitis (NASH) is an important cause of cirrhosis and liver transplantation in patients with type 2 diabetes in the United States.

1. Screening tools

ADA guidelines recommend the use of the Fibrosis-4 (FIB-4) index score (calculated based on age, ALT, AST, and platelets) as a screening tool. A score ≥1.3 is considered a high risk for clinically significant fibrosis, and a score above 2.6 is considered a very high risk.

Cusi, director of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, explained: "The reason we recommend using the FIB-4 index instead of liver enzymes as the ADA has recommended in the past is that now we know that 70% of T2DM patients already have steatosis, about one in five patients have fibrosis, and if only liver enzymes were used, the majority would be missed."

2. Treatment: lifestyle changes + GLP-1RA or pioglitazone

ADA pointed out that all adult patients with diabetes or prediabetes and NAFLD should change their lifestyle (especially when they are overweight or obese), and it is recommended to consider GLP-1RA, which is beneficial to nonalcoholic steatohepatitis, as a weight loss lifestyle. adjuvant therapy with modality intervention. Pioglitazone or GLP-1RA is the drug of choice for the treatment of hyperglycemia in adults with biopsy-proven NAFLD and type 2 diabetes. Insulin is the drug of choice for the hypoglycemic treatment of decompensated liver cirrhosis in adults with type 2 diabetes.

Specific suggestions are as follows:

➤ Recommendation 4.11a: It is recommended that adult patients with type 2 diabetes or prediabetes (especially those with obesity or cardiometabolic risk factors/established cardiovascular disease) should be screened/risk stratified with For nonalcoholic fatty liver disease with clinically significant fibrosis (defined as moderate fibrosis to cirrhosis), it is recommended to calculate the "Fibrosis-4 index (FIB-4, calculated according to age, ALT, AST, and platelets)". B

➤ Recommendation 4.11b: In adult patients with diabetes or prediabetes who have persistently elevated plasma transaminase levels for >6 months and a low FIB-4 index, other causes of liver disease should be evaluated. B

➤ Recommendation 4.12: Adults with type 2 diabetes or prediabetes with an indeterminate or high FIB-4 index should be additional risk stratified by liver stiffness as measured by transient elastography or liver fibrosis enhanced by blood biomarkers. B

➤ Recommendation 4.13: Adults with type 2 diabetes or prediabetes who have inconclusive results or are at high risk for significant liver fibrosis (i.e., by Fibrosis-4 index, liver stiffness measurements, or increased liver fibrosis) should be referred to a gastroenterologist or Hepatologist for further examination. Multidisciplinary treatment is recommended for long-term management. B

➤ Recommendation 4.14: Adults with type 2 diabetes or prediabetes, especially those who are overweight or obese with NAFLD, should be advised to make lifestyle changes to promote weight loss, ideally by incorporating a structured nutrition program and physical activity program, to promote cardiometabolic benefit (B) and histological improvement. C

➤ Recommendation 4.15: For adult patients with type 2 diabetes and NAFLD (especially if they are overweight or obese), consider GLP-1RA, which has proven beneficial effects on nonalcoholic steatohepatitis, as an adjunct to weight-loss lifestyle interventions. B

➤ Recommendation 4.16: Pioglitazone or GLP-1RA is the treatment of choice for adults with NAFLD and T2DM who are hyperglycemic or who are at high risk of NAFLD and have clinically significant fibrosis by noninvasive testing. A

➤Recommendation 4.17a: In adult patients with type 2 diabetes and NAFLD, hypoglycemic therapy other than pioglitazone or GLP-1RA can be continued according to clinical indications, but there is no evidence of the benefit of these treatments for nonalcoholic steatohepatitis.

➤ Recommendation 4.17b: Insulin is the drug of choice for the treatment of hyperglycemia in adults with type 2 diabetes and decompensated cirrhosis. C

➤Recommendation 4.18a: Cardiovascular risk is increased in adults with type 2 diabetes mellitus and NAFLD. Therefore, comprehensive management of cardiovascular risk factors is recommended. B

➤ Recommendation 4.18b: Statin therapy is safe for adults with type 2 diabetes and compensated cirrhosis with nonalcoholic fatty liver disease and should be initiated or continued as clinically indicated to reduce cardiovascular risk. (B) In patients with decompensated cirrhosis, given limited safety and efficacy data, statins should be used with caution and close monitoring. (B)

➤ Recommendation 4.19a: For adult patients with type 2 diabetes and nonalcoholic steatohepatitis B, metabolic surgery should be considered as an option for the treatment of nonalcoholic steatohepatitis to improve cardiovascular outcomes. B

➤ Recommendation 4.19b: Metabolic surgery should be used with caution in adults with type 2 diabetes and compensated cirrhosis due to nonalcoholic fatty liver disease B and is not recommended for decompensated cirrhosis. B

Update 2: Moving disease management forward—emphasizing the role of islet autoantibodies in type 1 diabetes screening

The new version of the ADA guidelines pointed out that according to a new drug recently approved by the US Food and Drug Administration (FDA) to delay the onset of type 1 diabetes, the content of the chapter "Classification and Diagnosis of Diabetes" should be updated to improve the screening of type 1 diabetes, Diagnosis-related content to echo FDA’s current guidance on intervention strategies to delay the onset of type 1 diabetes:

➤Recommendation 2.5: Screening for pre-symptomatic type 1 diabetes can be done by detecting insulin autoantibodies, glutamic acid decarboxylase autoantibodies, islet cell antigen 2 autoantibodies, or zinc transporter 8 antibodies. B

➤Recommendation 2.6: The existence of multiple islet autoantibodies is a risk factor for clinical type 1 diabetes, and the detection of abnormal blood sugar can be used for short-term risk prediction. When a patient is found to have multiple islet autoantibodies, referral to a diabetes center for further evaluation and/or consideration of clinical trials or approved treatment options should be considered to potentially delay the development of clinical type 1 diabetes. B

Update 3: For patients with type 1 diabetes in stage 2, consider Teplizumab-mzwv treatment

The new version of the ADA guidelines pointed out that according to a new drug recently approved by the FDA to delay the onset of type 1 diabetes, the content of the chapter "Preventing or delaying type 2 diabetes and related complications" of the guideline should be updated to improve the screening and diagnosis of type 1 diabetes. Content to echo FDA's current guidance on intervention strategies to delay the onset of type 1 diabetes:

➤ Recommendation 3.14: Teplizumab-mzwv treatment should be considered in patients with stage 2 type 1 diabetes aged ≥8 years to delay the onset of symptomatic type 1 diabetes. B

Teplizumab is approved to delay the onset of stage 3 type 1 diabetes in adults and children with stage 2 diabetes who are 8 years of age and older, based in part on efficacy results from a study of relatives at risk for type 1 diabetes. In the study, 44 people were randomly assigned to receive 14 days of teplizumab and 32 were randomly assigned to receive a placebo. In a Cox proportional hazards model stratified by age and oral glucose tolerance test status at randomization, the median time to diagnosis of stage 3 type 1 diabetes was 50 months in the teplizumab group and 25 months in the placebo group, At a median follow-up of 51 months, the difference was 25 months. The most common adverse reaction was lymphopenia (73%), followed by a rash (36%).

At present, a large number of clinical studies are being carried out on "preventing or delaying the onset of type 1 diabetes in stage 3". Some preliminary promising results.

how does Cistanche treat kidney disease? 

Cistanche has been used in traditional Chinese medicine to treat kidney diseases for centuries. It is believed to help improve the overall health of the kidneys and benefit kidney function. Cistanche is a natural herb, and its active ingredients, known as phenylethanoids, have been found to possess antioxidant, anti-inflammatory, and immunomodulatory properties.

Studies have suggested that Cistanche can help improve the functioning of the kidneys by increasing the production of urine, reducing proteinuria (excess protein in the urine), decreasing levels of creatinine (a waste product), and increasing the glomerular filtration rate (GFR). It has also been found to reduce inflammation, oxidative stress, and fibrosis of the kidney, making it a potential treatment for kidney diseases.

In addition, Cistanche has been found to help reduce uremia (high levels of urea in the blood), improve kidney function, and reduce the risk of kidney damage in patients with chronic kidney disease. It may also help reduce the risk of kidney failure in patients with diabetes.

Cistanche has also been found to help protect the kidneys from damage caused by drugs and toxins. Studies have shown that it can reduce the levels of toxic substances in the blood, including lead, cadmium, and mercury.

Finally, Cistanche may help reduce the risk of developing chronic kidney disease. Studies have suggested that it can help reduce the levels of inflammatory cytokines, which are associated with the development and progression of the disease.

Overall, Cistanche has many potential health benefits for the kidneys, and it may be an effective treatment for kidney diseases. However, more research is needed to confirm its effectiveness and safety.

References:

[1]Addendum. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S19–S40

[2]Addendum. 3. Prevention or Delay of Type 2 Diabetes and Associated Comorbidities: Standards of Care in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S41–S48

[3]Addendum. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S49–S67