Diabetes mellitus and fatty liver disease: Which comes first?

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Article Information:


Group: 2010
Subgroup: Volume 8, Issue 3, Summer
Date: September 2011
Type: Editorial
Start Page: 130
End Page: 131

Authors:

  • Seyed Moayed Alavian
  • Baqiyatallah Research Center for Gastroenterology and Liver Disease, Tehran, IR.Iran

      Correspondence:

      Affiliation: Baqiyatallah Research Center for Gastroenterology and Liver Disease
      City, Province: Tehran,
      Country: IR.Iran
      Tel:
      Fax:
      E-mail: alavian@thc.ir

Abstract:


 


Implication for health policy/practice/research/medical education:
The diabetes mellitus as a important part of metabolic syndrome is an emerging disease and association with fatty liver is very common. Reading this editorial is recommended to all family physicians, internists, gastroenterologists, endocrinologists and health policy makers.


 

Please cite this paper as:

Alavian SM. Diabetes mellitus and fatty liver disease: which comes first? Int J Endocriol Metab. 2010;8(3):130-1

Keywords: Diabetes Mellitus;Fatty liver Disease;Metabolic Syndrome

Manuscript Body:


Metabolic syndrome is an emerging problem in the world (1). Diabetes mellitus is one of the main parts of metabolic syndrome, and insulin resistance, hypertension, low HDL cholesterol, and hypertriglyceridemia are other parts of this syndrome (2). There is a worldwide epidemic of diabetes and obesity, with an estimated one billion overweight adults (3). It has been reported that the prevalence of metabolic syndrome in Iran is one of the highest worldwide (1). Metabolic syndrome is the disease that has changed the scientific knowledge in the new millennium. Nonviral diseases such as coronary heart disease and cerebrovascular accident were major global pandemics at the start of the 21th century. As risk factors for these diseases, physicians gave more attention to diabetes, hypertension, hyperlipidemia, and obesity. But now a new epidemic is emerging, metabolic syndrome, which is a cause of all risk factors for cardiovascular and cerebrovascular problems. As its name suggests, it is a syndrome i.e., a series of presentations that collectively form a categorization of pathophysiology, so metabolic syndrome is still forming and changing. Fatty liver disease has been diagnosed as an incidental finding in abdominal ultrasonography with a diffuse increase in echo texture (bright liver), increased liver echo texture compared with the kidneys, vascular blurring, and deep attenuation (4). Fatty liver disease can be found in patients with diabetes mellitus and obesity or can be diagnosed in individuals without these diseases. This raises questions regarding the influence of fatty liver disease on mortality and the risk of diabetes in the future (5). The spectrum of disorders related to obesity is wide, but the most important are insulin resistance, type 2 diabetes mellitus, abnormality in lipid profiles, high blood pressure, cardiovascular disease, stroke (6), and fatty liver disease (7, 8). Fatty liver disease in its more progressed phase, nonalcoholic steatohepatitis (NASH), is a component of metabolic syndrome and its consequences, and it is not surprising that elevations in ALT activity are frequently present in people with diabetes mellitus and cardiovascular disease and are associated with increased mortality (9). Liver-function tests are the most frequently ordered tests in clinical practice, being relatively cheap and easy to measure. ALT is the most common screening test for necro-inflammation in the liver, but it can be abnormal in the presence of inflammation and if most of the low-grade fatty liver is in the normal range. Elevations in ALT activity usually reflect the presence of fatty liver and are associated with obesity, cardiovascular disease, cerebrovascular disease, hypertension, and mortality. An abnormal ALT level should be viewed as an indicator of metabolic syndrome and should be addressed quickly. These patients are more likely to die of cardiovascular disease than from liver disease (4). Markers of insulin resistance are impaired glucose metabolism, hypertriglyceridemia, and fatty liver. The liver is a main site of glucose reuptake and also glycogenolysis. So, changing the responsiveness of liver to insulin effects (i.e., hepatic insulin resistance will disturb the whole body metabolism of glucose). On the other hand, when the process of insulin resistance and metabolic syndrome begins, it may cause increased fat deposits in the body and liver of animals. The abnormal ALT can predict for occurrence of diabetes mellitus in future.
Furthermore, metabolic syndrome and insulin resistance are more common in patients infected with hepatitis C virus (HCV) and hepatitis B virus (HBV), and the prevalence in increasing today (10). The degree of fibrosis is higher in these patients with coincidental diabetes mellitus and fatty liver disease (11, 12). There is a wide range in the prevalence of glucose metabolism alterations in cirrhotic patients in various studies (12, 13). The frequency of diabetes mellitus increases significantly with the severity of the liver disease both in cirrhotic cases and in patients with chronic hepatitis. These findings suggest that liver fibrosis, but not cirrhosis itself, is the event associated with glucose intolerance (12). But the multivariate analysis indicates an independent association between chronic hepatitis and DM rate, despite the fact that we compared diabetes mellitus occurrence among three groups who all suffered from liver disease. This theory states that occurrence of insulin resistance initially facilitates lipolysis and increases free fatty acid deposition in the liver, which increases products of lipid peroxidation inducing oxidative stress. This results in cytokine-mediated hepatic inflammatory damage that induces collagen deposits and eventually fibrosis.
In conclusion, a high prevalence of diabetes mellitus in patients with fatty and nonfatty liver share a common pathophysiology, and doctors should alert their patients that fatty liver puts them at high risk of acquiring diabetes mellitus and cardiovascular disease in the future. In fact, the risk of diabetes mellitus, its complications, and cardiovascular disease are more important than the progression of fatty liver to end-stage liver disease. Unfortunately, most affected persons are asymptomatic, and they are unaware of their endocrine abnormality. This finding highlights the importance of periodic screenings of individuals at high risk for metabolic syndrome.

References: (13)

  1. Azizi F, Salehi P, Etemadi A, Zahedi-Asl S. Prevalence of metabolic syndrome in an urban population: Tehran Lipid and Glucose Study. Diabetes Res Clin Pract. 2003;61(1):29-37. [Pub med]
  2. Azizi F, Hadaegh F, Khalili D, et al. Appropriate definition of metabolic syndrome among Iranian adults: report of the Iranian National Committee of Obesity. Arch Iran Med. 2010;13(5):426-8. [Pub med]
  3. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol. 2007;13(17):2436-41. [Pub med]
  4. Poustchi H, George J, Esmaili S, et al. Gender differences in healthy ranges for serum alanine aminotransferase levels in adolescence. PLoS ONE. 2011;6(6):e21178. [Pub med]
  5. Daryani NE, Alavian SM, Zare A, et al. Non-alcoholic steatohepatitis and influence of age and gender on histopathologic findings. World J Gastroenterol. 2010;16(33):4169-75. [Pub med]
  6. Gharouni M, Rashidi A. Association between Fatty Liver and Coronary Artery Disease: Yet to Explore. Hepat Mon. 2007;7(4):243-2244. [Link]
  7. Alavian SM, Mohammad-Alizadeh AH, Esna-Ashari F, Ardalan G, Hajarizadeh B. Non-alcoholic fatty liver disease prevalence among school-aged children and adolescents in Iran and its association with biochemical and anthropometric measures. Liver Int. 2009;29(2):159-63. [Pub med]
  8. Lazar MA. How obesity causes diabetes: not a tall tale. Science. 2005;307(5708):373-5. [Pub med]
  9. Sattar N, Scherbakova O, Ford I, et al. Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study. Diabetes. 2004;53(11):2855-60. [Pub med]
  10. Mohammad-Alizadeh AH, Fallahian F, Alavian SM, et al. Insulin resistance in chronic hepatitis B and C. Indian J Gastroenterol. 2006;25(6):286-9. [Pub med]
  11. Alavian SM. Diabetes, renal failure and hepatitis C infection: The puzzle should be attended more in future. Nephro-Urol Mon. 2011;3(3):153-4. [Pub med]
  12. Alavian SM, Hajarizadeh B, Nematizadeh F, Larijani B. Prevalence and determinants of diabetes mellitus among Iranian patients with chronic liver disease. BMC Endocr Disord. 2004;4(1):4. [Pub med]
  13. Alavian SM, Ramezani M, Bazzaz A, Azizabadi Farahani M, Behnava B, Keshvari M. Frequency of Fatty Liver and Some of Its Risk Factors in Asymptomatic Carriers of HBV Attending the Tehran Blood Transfusion Organization Hepatitis Clinic. Iran J Endocrino Metabol. 2008;10(2):99-106. [Pub med]