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Link Between Serum Bilirubin and Diabetic Retinopathy in Type 2 Diabetes Patients

Serum bilirubin is inversely correlated with diabetic retinopathy predicting progression of retinopathy over time.

 Bilirubin is a breakdown of hemoglobin resulting in a yellowish pigment found in bile. When older red blood cells are replaced by newer red blood cells, bilirubin remains. The liver breaks down bilirubin by allowing it to be excreted in the feces. High levels of bilirubin can lead to jaundice, which is a yellow tinge in one’s skin or eyes. Jaundice can indicate liver or gallbladder problems. However, serum bilirubin has a distinct role in anti-inflammatory, antioxidant, and immunological properties, and protects against microvascular and cardiovascular complications associated with diabetes. Among many microvascular complications caused by diabetes, diabetic retinopathy remains the leading cause of blindness in the world. Past studies have shown that individuals with higher levels of bilirubin are at a decreased risk of developing diabetes mellitus. Moreover, markers of inflammation and insulin resistance were also low among patients with high serum bilirubin levels. This article will focus on studies observing the effects of bilirubin on diabetic microvascular complications, particularly diabetic retinopathy.

In a recent study titled “Association of Serum Total Bilirubin Level With Diabetic Retinopathy in Type 2 Diabetes Mellitus,” researchers aimed to discover a link between total serum bilirubin concentrations and diabetic retinopathy. in this case control study conducted at the Department of Endocrinology, Diabetes and Metabolic Disease at Hayatabad Medical Complex, individuals with diabetes were observed between March 2015 and February 2016. Individuals included were those who were 18 years or older and had a 6 month or more standing diagnosis of diabetes mellitus. There were a total of 152 patients enrolled in the study where 76 were cases and 76 were controls.

Demographic data and medical histories were gathered. After an informed consent was obtained from each individual, groups of two were formed. Those with both diabetes mellitus and diabetic retinopathy were part of the cases group and individuals with diabetes mellitus but no diabetic retinopathy were placed in the control group. An individual was diagnosed with diabetic retinopathy using stereoscopic fundus photographic imaging. Individuals excluded from the study were those with liver disease, hemolytic anemia, any history of chronic alcohol consumption, use of hepatotoxic drugs like anti-epileptics or anti-tuberculosis, and finally women who were using oral contraceptives. Each included participant underwent ophthalmic examinations at the Diabetic Retinopathy Screening Clinic. In addition, blood was drawn to measure complete blood counts, serum total bilirubin levels, random blood glucose levels, serum creatinine and HbA1c. A student t-test was used to compare data between both groups in numerical values. A chi-square test compared proportions between both groups and the Kendall’s tau b test was used to measure the sets of original data.

Results showed that patients with diabetic retinopathy had a longer duration of diabetes (p=0.001), however, hemoglobin levels were lower (p=0.000) when compared with people with diabetes who do not have retinopathy. Serum total bilirubin levels were lower in cases compared to controls (p=0.002). Researchers found that a low hemoglobin level, longer duration of diabetes, and total serum bilirubin levels were independent with diabetic retinopathy.

Bilirubin can serve as both a harmful or protective substance in our bodies. Presence of bilirubin, if seen in high amounts, may lead to adverse effects in the human body like jaundice, kernicterus, or liver damage. If produced in normal amounts, bilirubin serves as an anti-inflammatory or an antioxidant. In this study, researchers discovered that there were lower serum bilirubin concentrations among diabetes patients with retinopathy compared to diabetes patients without retinopathy. Moreover, they concluded that the presence of low bilirubin levels was inversely related to the development of diabetic retinopathy. In addition, they found that a rise in the development of retinopathy is associated with increasing serum total bilirubin levels as well as poorly controlled blood glucose levels and a long-standing diagnosis of diabetes. Some limitations to the study included the association between diabetic retinopathy and serum bilirubin levels that does not prove a causal relationship. Furthermore the study was based on a single serum bilirubin measurement and fundi examination, however each individual may have different levels of bilirubin over time. Lastly, the limited sample size studied was also a limitation to the study. Further studies are required to determine an exact causal relationship between serum bilirubin and diabetic retinopathy before one can consider that a low serum bilirubin level leads to retinopathy among diabetes patients.

Practice Pearls:

  • Serum bilirubin levels have positive and negative effects depending on the amount found in the human body.
  • Low serum bilirubin levels are often seen in diabetes patients.
  • A low serum bilirubin level is proposed to increase the prevalence of diabetic retinopathy.

Ghaffar, Tahir, Zahid Irfan Marwat, Fahim Ullah, Salman Khan, and Aziz Ul Hassan Aamir. “ASSOCIATION OF SERUM TOTAL BILIRUBIN LEVEL WITH DIABETIC RETINOPATHY IN TYPE 2 DIABETES MELLITUS.” Journal of Ayub Medical College Abbottabad. N.p., n.d. Web. 19 July 2017.


Nuha Awad, Doctor of Pharmacy Candidate: Class of 2018; LECOM College of Pharmacy