HbA1c in Liver Transplant

patients
Dr D Madhavi
Consultant Biochemist
Yashoda Hospitals
Secunderabad
 Liver is one of the most commonly transplanted organ.
 The most common indication for Liver transplantation is Cirrhosis
followed by primary liver tumors and cholestatic disease (primary
biliary cirrhosis or extra hepatic biliary atresia).
 Diabetes is a disorder of chronic hyperglycemia. It has been
subdivided into
• Type 1 diabetes (with autoimmune destruction of insulin-
secreting β cells).
• Type 2 diabetes (T2DM; with insulin resistance and features of
metabolic syndrome).
 The fasting plasma glucose (FPG) test, 75 g oral anhydrous glucose
tolerance test (OGTT), measurement of random plasma glucose and
glycated hemoglobin (HbA1c) values are four methods used to
diagnose diabetes.
 Diabetes mellitus has become a global epidemic its complications
pose a major health threat worldwide . Diabetes mellitus is
recognized as the ninth major cause of death.
 China and India are the top two epicenters of this global epidemic
 Though genetic predisposition in part plays a role in the
susceptibility to T2DM, but an unhealthy diet and a sedentary
lifestyle are the major risk factors of the current global epidemic.
 Disorders of glucose metabolism, ranging from impaired glucose
intolerance to diabetes mellitus, are frequently encountered in
patients with chronic liver diseases.
 CLD is one of the major causes of death in diabetic patients .
 Thus there is a close relationship between CLD and diabetes.
 The liver plays a central role in glucose metabolism. Almost all
patients with cirrhosis are insulin-resistant, 60% to 80% are glucose
intolerant, and about 20% develop diabetes.
 Cirrhosis is associated with portosystemic shunts and also reduced hepatic
mass, which can cause impairment of the clearance of insulin by the liver
which may contribute to peripheral insulin resistance through down-
regulation of insulin receptors.
 Also, cirrhosis is known to be associated with increased levels of
advanced-glycation-end products which play a role in the development of
diabetes.
 Diabetes mellitus itself is an independent factor for poor prognosis
in patients with cirrhosis.
 Diabetes mellitus is also associated with the occurrence of major
complications of cirrhosis, such as ascites and renal dysfunction,
hepatic encephalopathy and bacterial infections.
 Diabetes mellitus is also shown to be associated with an increased
risk of hepatocellular carcinoma in patients with chronic liver
diseases.
 It is important to maintain a good glycemic control status because
patients with CLD and inadequate blood glucose control have poor
prognosis.
 The main feature of blood glucose dynamics in patients with CLD is
marked blood glucose fluctuations, such as postprandial
hyperglycemia and nocturnal hypoglycemia.
 Glycated hemoglobin (GHb) is the result of irreversible non-enzymatic
glycation at amino terminal valines of the hemoglobin chain.
 Glycated hemoglobin reflects the previous 2-3 months of glycemic control
 However the HbA1c results can be skewed in certain conditions that alter
the lifespan of red blood cells in the body as well as in people with
haemoglobinopathies.
 HbA1c is also affected by age, ethnicity and pregnancy
 It is to be noted that anemia, portal hypertension, hypersplenism, and
variceal bleeding in Chronic Liver disease can alter the lifespan of red
blood cell (RBC) survival and thus alteration of HbA1c
 The ADA guidelines indicate considering alternate diagnostic tests
(fasting plasma glucose test or oral glucose tolerance test) if there is
disagreement between Hb A1c and blood glucose levels.
 In our study we evaluated the utility of HbA1c as a marker of
glycemic status in those patients posted for liver transplantation.
 A retrospective analysis of the HbA1c values were done in 50
patients who were posted for Liver Transplant during the time
period November 2015 to November 2018.
 The estimated average glucose (eAG) was calculated from the
HbA1c values.
 The comparison was done between the measured glucose and
estimated average glucose. The comparison was done with Random
blood sugar (RBS) in 21 patients and with Fasting Blood Sugar
(FBS) in 29 patients.
 F B S v e rsu s e A G
200
180
160
140
120
100
80
60
40
20
0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29

FBS eAG
 Slope 0.2976

y-intercept 75.5575

Sresid 21.6610

r 0.1881
 R B S v e rsu s e A G
200
180
160
140
120
100
80
60
40
20
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

RBS eAG
 Slope 0.7776

y-intercept 57.5164

Sresid 27.0070

r 0.3439
 The 'r' value was 0.1881 for FBS versus eAG. Though a positive
correlation, the relationship is weak as the nearer the value is to zero, the
weaker the relationship. The value of R2, the coefficient of determination,
is 0.0354. The t-value is 5.1241. The p-value is < .00001. The result is
significant at p< .05.
 The 'r' value was 0.3439 for RBS versus eAG. Though a positive
correlation, the relationship is weak as the nearer the value is to zero, the
weaker the relationship. The value of R2, the coefficient of determination,
is 0.1183. The t-value is 6.0225. The p-value is < .00001. The result is
significant at p < .05.
 We conclude that HbA1c may not be a reliable marker in patients
posted for Liver transplant surgeries and should be interpreted with
caution in such patients taking into account liver function tests and
other glycemic markers.
 Alternative tests such as fructosamine, glycated albumin and 1,5-Anhydro-
glucitol are also affected by liver cirrhosis and cannot be routinely
recommended.
 To date, the best option for diagnosing diabetes in patients with liver
cirrhosis is the oral glucose tolerance test, as fasting blood glucose and
HbA1c levels may be normal despite diabetes.
 For monitoring diabetes, self-blood glucose monitoring and continuous
glucose monitoring are suitable options, especially for those with more
advanced liver disease in whom HbA1c is not a reliable parameter of
glycemic control.
 CLD-HbA(1C) was defined as the average of measured HbA(1C)
and GA/3.
 While measured HbA(1C) levels in patients with CLD were
generally lower than estimated HbA(1C) levels, GA/3 values were
generally higher than estimated HbA(1C) levels.
 CLD-HbA(1C) has been found a superior chronic glycemic control
marker than HbA(1C) or GA in diabetic patients with chronic liver
diseases.
Thank You