Diabetes And Hepatic Dysfunction: Exploring the Complex Connection in Metabolic Health

Abstract

Chronic liver diseases and diabetes are sized health challenges worldwide; the two conditions demonstrate a multifaceted and reciprocal association that is cropping up more frequently in clinical practice and scientific investigations. More importantly, liver as an organ, has fundamental function in control of glycometabolic homeostasis and liver disease can certainly also exacerbate insulin resistances which in turn leads to the development of diabetes. On the other hand, diabetes and most especially type 2 diabetes are risk factors for NAFLD, which is the most prevalent liver disease in metabolic syndromes. NAFLD may further progress to more aggressive liver diseases, NASH, cirrhosis and HCC. Possible molecular level linkages include interference with lipid metabolism, inflammation and oxidative stress as well as changes in the overall digestive tract bacterial flora. Moreover, both conditions have risk factors, including obesity, dyslipidemia, and hypertension, which contribute to factors that interact between them. Therefore, this review will attempt to provide an overview of the literature concerning hepatic injury and diabetes, the pathophysiologic connections, diagnostic concerns, and therapies for dealing with these complicated conditions. It is incumbent upon health educators, clinicians, and policymakers to comprehensively understand this relationship so that innovative strategies based on this positive association will facilitate early adoption of successful diagnosis and prevention and treatment measures of both liver diseases and diabetes in which the burden impact of both diseases overlap immensely.

Keywords

Introduction

Figure 1: Different Types of Diabetes

The cause of the disease is due to hereditary factors, environmental factors, malfunction of the immune system and metabolic problems and HLA types, insulin autoantibodies and pro-inflammatory cytokines play important roles ^[9].

Figure 2: Liver Diseases

Importance of Studying the Diabetes-Liver Disease Link

Figure 3 : Diabetes-Liver Disease Link

Problems the Liver Encounter in Diabetes

1. NAFLD is the most frequent liver problem seen in those with diabetes; it sometimes becomes NASH or even cirrhosis.

2. Diabetics are more likely to get hepatitis B or C.

3. Cirrhosis is the late stage of liver disease resulting in scarring and liver failure.

4. Chronic liver inflammation in diabetes seems to strongly increase the risk of Hepatocellular Carcinoma (HCC) ^[21] .

Insulin Resistance and Hepatic Dysfunction

Insulin resistance is very important in the development of T2DM and liver diseases. Hepatitis C Virus (HCV): The core proteins present in the virus interact with the insulin receptors to block insulin signaling.High free fatty acid release from adipose tissue leads to fat buildup in the liver, causing insulin resistance in NAFLD. As a result of liver damage, insulin stops suppressing liver glucose production. In addition, changes in adiponectin, leptin, TNF-α and IL-6 in the body contribute to the overall resistance to insulin in both the liver and other organs ^[22]  .

The NAFLD–Diabetes Connection

The condition ranges from simple fat accumulation in the liver to serious complications like non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and HCC. Many experts say that type 2 diabetes is linked to an increased likelihood of NAFLD. On the other hand, NAFLD may make insulin resistance stronger and make type 2 diabetes more likely.

Type 2 diabetes is linked to NAFLD which impacts between 60% and 80% of patients. Some of the mechanisms both share are:

5. Lipotoxicity (the harmful impact of lipids) and ectopic fat storage

5. Pro-inflammatory cytokines are secreted by the body (such as TNF-α and IL-6).
   5. Trouble caused by free radicals
   5. Problems with the mitochondria

At first, many cases of NAFLD happen without noticeable symptoms and serious illness is usually silent until it has advanced. Helping diabetics improve NAFLD is important for lowering their likelihood of serious complications  ^[23,24]  .

Progression to Liver Fibrosis and Cirrhosis in Diabetics

People with Type 2 diabetes are at greater risk of developing and progressing liver fibrosis and cirrhosis. Insulin resistance causes people to develop:

• The hepatic stellate cells are activated.
• There’s more unwanted extracellular matrix becoming present
• Fibrogenesis

There is good evidence from many large studies that people with diabetes are at least twice as likely to die from liver disease. Patients who do not manage their diabetes well risk worse outcomes and higher levels of fibrosis when they have chronic hepatitis B or C. Having diabetes and liver disease together causes faster progression of liver disease, regardless of the rest of the metabolic syndrome. Knowing about these interactions helps with early classification of risk and planning interventions ^[25].

Therapeutic Approaches for Co-Existing Diabetes and Liver Disease

Lifestyle Modifications and Comorbidity Management

Modifications in lifestyle are essential for the management of both liver disease and diabetes:

5. Weight loss of 5-10% can lead to major improvements in liver enzymes and the appearance of the liver.
5. Monounsaturated fats and little sugar are found in the Mediterranean diet which is a great choice.
5. Exercise: Makes insulin work more effectively and lessens the amount of fat in the liver.
5. Avoiding alcohol is very important for those with NAFLD and alcohol-related liver disease ^{[26]     .}

Managing Comorbidities:

5. Cardiovascular disease and liver disease are usually found together because they have many similar risk factors.

5. Markers like the FIB-4 index can be used to keep track of liver fibrosis without interfering with the patient.
5. Being treated by a hepatologist, endocrinologist and cardiologist is very important ^[35].

Pharmacological Treatments

Several antidiabetic agents show potential in managing liver disease:

1. Metformin Taking metformin helps insulin respond better to glucose in the blood, but has a little impact on the appearance of liver tissue ^[36].

2. Pioglitazone (a PPAR-γ agonist): Improves steatosis and reduces inflammation in cases of NASH; is used for T2DM ^[29].

3. GLP-1 Receptor Agonists (e.g., liraglutide): These GLP-1-like pills (such as liraglutide) help handle fat in the liver, as well as managing blood sugar and weight.

4. SGLT2 Inhibitors: Help control blood sugar and might be helpful in decreasing ascites and liver fat ^{[28]   .}

5.Tripeptide, Lanifibranor, Resmetirom, Obeticholic acid and Elafibranor are promising drugs for the management of NASH/NAFLD. They have the ability to control glycaemia as well as improve liver disease, but more work is necessary to make sure they are safe and effective for a long period ^{[30, 31,32,33,34]}

CONCLUSION

Finally, there is a two-way interaction between diabetes and liver disease in which the two conditions worsen each other. Lack of insulin action or resistance is the prominent characteristic of T2D and enhances the chance of getting liver diseases such as NAFLD, which can develop to NASH, cirrhosis and liver failure. On the other hand, liver diseases especially those complicated with metabolic disorders have impact on carbohydrate metabolism and insulin sensitivity and therefore compounding the status of diabetes. Possible connections between diabetes and liver disease include metabolic changes such as insulin resistance and inflammation, oxidative stress, fatty liver and damage of liver cells. Further, glucose and lipid metabolism occur mainly in the liver the reason why this organ is involved centrally in the pathophysiology of both conditions. Specifically, NAFLD has been found to be related to increased cardiovascular events and higher mortality rate in diabetic population, which again proved the clinical importance of this relationship. Diabetes and liver disease share so many similarities that they both have to be managed with a combination of TS; that is: TS of diet and physical activity and pharmacological management, which aims at improving insulin sensitivity and monitoring liver Function. Since both conditions are on the rise, and their optimal treatment has not been well documented, there is a need to address this comorbidity by improving the screening and diagnosis of these two diseases and develop appropriate therapies.  As suggested in this study, additional investigations should be dedicated to a better understanding of the molecular-to-inflammatory pathways that connect diabetes with the liver and generate novel multidirectional therapeutic approaches to enhancing the prognosis of affected patients.

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