Utility and Limitations of Glycated Hemoglobin (HbA1c) in Patients with Liver Cirrhosis as Compared with Oral Glucose Tolerance Test for Diagnosis of Diabetes

Diabetes Ther https://doi.org/10.1007/s13300-017-0362-4 ORIGINAL RESEARCH Utility and Limitations of Glycated Hemoglobin (HbA1c) in Patients with Liver Cirrhosis as Compared with Oral Glucose Tolerance Test for Diagnosis of Diabetes Tejasav Sehrawat . Anuraag Jindal . Paaras Kohli . Amit Thour . Jasbinder Kaur . Atul Sachdev . Yashdeep Gupta Received: December 5, 2017 Ó The Author(s) 2018. This article is an open access publication ABSTRACT Introduction: To study the utility of glycated hemoglobin (HbA1c) in the diagnosis of diabetes in patients with cirrhosis as compared to the gold standard oral glucose tolerance test (OGTT) and to see the effect of anemia and severity of cirrhosis on its performance. Methods: Individuals (n = 100) with an established diagnosis of liver cirrhosis were recruited. The OGTT was performed as described by the World Health Organization (WHO). The Enhanced content To view enhanced content for this article go to http://www.medengine.com/Redeem/ 3E1DF060406A1CCC. At the time of carrying out this study, A. Jindal and Y. Gupta were affiliated to Department of Internal Medicine, Government Medical College and Hospital, Chandigarh, India. T. Sehrawat
P. Kohli
A. Thour
A. Sachdev Department of Internal Medicine, Government Medical College and Hospital, Chandigarh, India A. Jindal Department of Gastroenterology, Columbia Asia Hospital, Patiala, India J. Kaur Department of Biochemistry, Government Medical College and Hospital, Chandigarh, India Y. Gupta (&) Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India e-mail: severity of cirrhosis was calculated using the Child–Turcotte–Pugh (CTP) score. The severity of anemia was defined according to WHO criteria. The utility of HbA1c was compared against the OGTT results. Test sensitivity and specificity were used to describe the diagnostic accuracy of HbA1c. Results: A total of 100 subjects aged 46.9 ± 9.1 years (mean ± standard deviation) participated in the study, of whom 65% were recruited from out patient department of our hospital. The overall sensitivity and specificity of a HbA1c level of C 6.5% for the diagnosis of diabetes in patients with cirrhosis was 77.1% (95% CI 59.9, 89.6) and 90.8% (95% CI 81.0, 96.5), respectively. The positive and negative predictive values were 81.8% (95% CI 67.3, 90.8) and 88.1% (95% CI 80.0, 93.2), respectively. The area under the curve was 0.85 (95% CI 0.75–0.94). The sensitivity of HbA1c for diagnosing diabetes in outpatients was 87.0% (95% CI 66.4, 97.2) and was better than that for diagnosing diabetes in hospitalized patients (58.3%; 95% CI 27.7, 84.8). The sensitivity of HbA1c for diagnosing diabetes was poor in patients with moderate to severe anemia. The difference in sensitivity and specificity was not statistically different for CTP classes A, B and C. The prevalence of diabetes as defined by American Diabetes Association OGTT criteria was 35% (95% CI 25.7–45.2%). Conclusions: Taking OGTT as the gold standard, the sensitivity of HbA1c for diagnosing Diabetes Ther diabetes is good when used in outpatients with cirrhosis. However, the sensitivity of HbA1c decreases when it is used for hospitalized patients, suggesting that it is not a good test for diagnosis of diabetes in such cases. It also performs poorly if the patient has moderate to severe anemia. Keywords: Hepatogenous diabetes; OGTT; Cirrhosis; Diagnosis HbA1c; INTRODUCTION Liver cirrhosis is a pathologically defined disease [1]. Histologically it is characterized by diffuse nodular regeneration surrounded by dense fibrotic septa. Subsequent parenchymal extinction and collapse of liver structures together cause pronounced distortion of hepatic vascular architecture [2]. Liver biopsy is the gold standard, but it is not been widely used in clinical practice as it is invasive and susceptible to sampling error and inter-observer discrepancy. Clinical diagnosis is preferentially made on the basis of patient history, physical examination, laboratory and imaging findings. In cases where there is discrepancy among the findings, liver biopsy is helpful for a definitive diagnosis of cirrhosis [1]. Hepatitis C virus, alcohol misuse, non-alcoholic fatty liver disease are the main causes of cirrhosis in developed countries, whereas infection with hepatitis B virus is the most common cause in sub-Saharan Africa and most parts of Asia [2]. Cirrhosis is the fourteenth most common cause of death worldwide and results in approximate 1.03 million deaths per year worldwide [3]. Diabetes is an independent factor for poor prognosis in patients with cirrhosis. Specifically, diabetes is associated with the occurrence of major complications of cirrhosis, including ascites, renal dysfunction, hepatic encephalopathy and bacterial infections. Diabetes is also associated with an increased risk of hepatocellular carcinoma and mortality in patients with chronic liver diseases [4]. Diabetes is a disorder of chronic hyperglycemia and has traditionally been subdivided into type 1 diabetes (with autoimmune destruction of insulin-secreting b cells) and type 2 diabetes (T2DM; with insulin resistance and features of metabolic syndrome) [5]. The fasting plasma glucose (FPG) test, 75 g oral glucose tolerance test (OGTT), measurement of random plasma glucose or glycated hemoglobin (HbA1c) values are four methods used to diagnose diabetes [6]. The global epidemic of diabetes mellitus and its complications pose a major health threat worldwide [7]. Diabetes mellitus is the ninth major cause of death [8]. The International Diabetes Federation (IDF) estimated that worldwide one in 11 adults aged 20–79 years (415 million adults) had diabetes mellitus in 2015. This estimate is projected to rise to 642 million by 2040. China and India are the top two epicenters [9]. Genetic predisposition partly determines individual susceptibility to T2DM, but an unhealthy diet and a sedentary lifestyle are important drivers of the current global epidemic. Early developmental factors (such as intrauterine exposures) also have a role in susceptibility to T2DM later in life [7]. Disorders of glucose metabolism, namely glucose intolerance and diabetes, are frequent in patients with chronic liver diseases. The prevalence of diabetes is higher in patients with cirrhosis than in those without cirrhosis [10]. In patients with cirrhosis, disorders of glucose metabolism range from mere glucose intolerance to overt diabetes. It is estimated that only 30% of these patients have normal glucose tolerance, with 30–50% having impaired glucose tolerance and up to 30% having overt diabetes. These values are much higher than those in the general population, where the prevalence of glucose intolerance is around 15% and that of diabetes is 8%. In patients with cirrhosis, diabetes can either be the classical T2DM or the socalled hepatogenous diabetes, i.e. a consequence of liver insufficiency and portal hypertension [4, (...truncated)