Lower HbA1c Levels Seen in Diabetic Liver Disease Patients

Diabetes is a leading cause of liver disease, with cirrhosis responsible for a considerable number of deaths in people with diabetes in the USA. The association is mediated by multiple mechanisms including dyslipidemia and altered hepatic fatty acid processing.

Glycated hemoglobin or HbA1c is now widely used for this purpose in primary care, resulting in a doubling of the number of HbA1c assessments requested, and a corresponding decrease in glucose measurement. Since 2014, the use of HbA1c testing has been included in the American Diabetes Association guidelines for the diagnosis of diabetes in hospital.


Scientists at the Queen Elizabeth Hospital (Birmingham, UK) and their colleagues collected HbA1c and random plasma glucose data for 125 people with diabetes without liver disease and for 29 people awaiting liver transplant with diabetes and cirrhosis. Cirrhosis was caused by non‐alcoholic fatty liver disease, hepatitis C, alcoholic liver disease, hereditary hemochromatosis, polycystic liver/kidneys, cryptogenic/non‐cirrhotic portal hypertension and α‐1‐antitrypsin‐related disease.

The team measured biochemical variables on the Roche c8000 analyzers and full blood count on Beckman DxH800 analyzers. HbA1c was measured in EDTA blood using an International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) aligned TOSOH G8 ion exchange high performance liquid chromatography analyzers.

The scientists reported that the median (interquartile range) HbA1c was 41 (32–56) mmol/mol [5.9%] (5.1–7.3) versus 61 (52–70) mmol/mol [7.7 (6.9–8.6) %] respectively, in the diabetes with cirrhosis group versus the diabetes without cirrhosis group. The glucose concentrations were 8.4 (7.0–11.2) mmol/L versus 7.3 (5.2–11.5) mmol/L. HbA1c was depressed by 20 mmol/mol (1.8%) in 28 participants with cirrhosis but elevated by 28 mmol/mol (2.6%) in the participant with α‐1‐antitrypsin disorder. Those with cirrhosis and depressed HbA1c had fewer larger erythrocytes, and higher red cell distribution width and reticulocyte count. This was reflected in the positive association of glucose with mean cell volume and hemoglobin level and the negative association for HbA1c in the diabetes group with cirrhosis.

The authors concluded that cirrhosis of the liver affects the accuracy of HbA1c results, leading to unreliable estimates of blood glucose over the previous 2 to 3 months. Anemia in people with cirrhosis awaiting liver transplant is associated with altered red blood cell morphology. The study was originally published in the May 2019 issue of the journal Diabetic Medicine.

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