Patients with Type 2 Diabetes Mellitus Accompanied by Elevated Serum CA19-9 Associated Not with Pancreatic Cancer but Interstitial Lung Disease

Introduction: CA19-9 is the most reliable tumor marker for pancreatic cancer, with 70–90% sensitivity, 90% specificity, 69% positive predictive value, and 90% negative predictive value. However, increased CA19-9 levels have been observed in benign conditions, pancreatitis, pulmonary disease, smoking, and hepatobiliary system disease. Numerous studies have reported that circulating CA19-9 levels are elevated during hyperglycemia in diabetes mellitus (DM) and have been associated with hemoglobin A1c (HbA1c). However, the precise mechanism behind increased serum CA19-9 levels in diabetes remains still unclear. Here, we report a case of type 2 DM (T2DM) accompanied by elevated serum CA19-9 levels due to not pancreatic cancer but interstitial pneumonitis. Case Report: The patient, a 73-year-old Japanese woman, was taking metformin (1,500 mg/day), repaglinide (1.5 mg/day), and sitagliptin (50 mg/day). Over the past year, she also took atorvastatin (5 mg/day) and azilsartan (40 mg/day). The patient had been followed up for systemic scleroderma (with low-dose steroid therapy) and mild interstitial lung disease (ILD) (without treatment) for a number of years at a different hospital. The patient’s peripheral blood laboratory findings were normal range. Her HbA1c level fluctuated between 7.0% and 8.0% in the past 6 months. Her CA19-9 level was fluctuated between 562.7 and 823.2 U/mL (normal <37), and her KL-6 level was fluctuated between 516 and 557 U/L (normal <500) in the past 6 months. Due to the marked increase in the CA19-9 level, an extensive screening examination was performed for malignancy, including abdominal ultrasound scan, computed tomography (CT), and magnetic resonance cholangiopancreatography, revealing no malignancy. We observed bilateral pulmonary lesions (bottom of lungs) and ground-glass opacity on the chest CT. The pancreatic monoclonal antigen type 2 (DU-PAN-2) level was <25 U/mL. Conclusions: In our case, CA19-9 levels were increased in association not with pancreatic cancer but with ILD. Thus, when T2DM is accompanied by elevated serum CA19-9 levels, attention needs to be paid not only to the presence of pancreatic cancer but also to the possible ILD. Especially, when diabetes and ILD are treated in different hospitals, diabetologists need to pay attention about the presence of hidden ILD besides DM.

[1]  F. Toledo,et al.  Understanding the Contribution of Insulin Resistance to the Risk of Pancreatic Cancer. , 2021, The American journal of gastroenterology.

[2]  Yasushi Tanaka,et al.  Proposed cut-off value of CA19-9 for detecting pancreatic cancer in patients with diabetes: a case-control study. , 2018, Endocrine journal.

[3]  M. Bolanowski,et al.  Diabetes and Cancer: a Review of Current Knowledge. , 2016, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[4]  S. Okada,et al.  Interstitial pneumonia during administration of dipeptidyl peptidase‐4 inhibitors , 2015, Journal of diabetes.

[5]  Y. Bao,et al.  Decreased serum CA19-9 is associated with improvement of insulin resistance and metabolic control in patients with obesity and type 2 diabetes after Roux-en-Y gastric bypass , 2014, Journal of diabetes investigation.

[6]  A. Esteghamati,et al.  CA 19-9 is associated with poor glycemic control in diabetic patients: role of insulin resistance. , 2014, Clinical laboratory.

[7]  H. Saito,et al.  Study on the mechanism causing elevation of serum CA19-9 levels in diabetic patients. , 2013, Endocrine journal.

[8]  Y. Bao,et al.  Serum CA19-9 Level Associated with Metabolic Control and Pancreatic Beta Cell Function in Diabetic Patients , 2012, Experimental diabetes research.

[9]  Yu Xu,et al.  Relationship between CA 19‐9 levels and glucose regulation in a middle‐aged and elderly Chinese population , 2012, Journal of diabetes.

[10]  Ü. Doğan,et al.  Relationship of CA 19-9 with choledocholithiasis and cholangitis. , 2011, The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology.

[11]  A. Mayadağlı,et al.  Type 2 diabetes mellitus and CA 19-9 levels. , 2007, World journal of gastroenterology.

[12]  M. Yamakado,et al.  Influence of Smoking on Serum Carcinoembryonic Antigen Levels in Subjects Who Underwent Multiphasic Health Testing and Services , 1998, Journal of Medical Systems.

[13]  Y. Totani,et al.  Serum CA19-9 Levels Reflect Bronchoalveolar Lavage Fluid Neutrophil Levels in Idiopathic Pulmonary Fibrosis , 2001, Respiration.

[14]  J. Fujita,et al.  Role of Carbohydrate Antigens Sialyl Lewis (a) (CA19-9) in Bronchoalveolar Lavage in Patients with Pulmonary Fibrosis , 2000, Respiration.

[15]  M. Duffy CA 19-9 as a Marker for Gastrointestinal Cancers: A Review , 1998, Annals of clinical biochemistry.

[16]  E. Pinès,et al.  [Unusually high level of CA 19-9 in chronic pancreatitis]. , 1995, Gastroenterologie clinique et biologique.

[17]  B. Vergès,et al.  Elevated serum CA19-9 levels in poorly controlled diabetic patients. Relationship with Lewis blood group. , 1994, Gastroenterologie clinique et biologique.

[18]  H. Mukae,et al.  Elevation of tumor-associated carbohydrate antigens in patients with diffuse panbronchiolitis. , 1993, The American review of respiratory disease.

[19]  S. Halimi,et al.  Influence of metabolic disturbances of diabetes mellitus on serum CA 19-9 tumor marker. , 1991, Diabete & metabolisme.

[20]  K. Naka,et al.  The effect of non-insulin-dependent diabetes on serum concentrations of tumor-associated carbohydrate antigens of CA19-9, CA-50, and sialyl SSEA-1 in association with the Lewis blood phenotype. , 1990, Clinica chimica acta; international journal of clinical chemistry.

[21]  W. Steinberg The clinical utility of the CA 19-9 tumor-associated antigen. , 1990, The American journal of gastroenterology.

[22]  F. Safi,et al.  Tumor markers in pancreatic cancer. Sensitivity and specificity of CA 19-9. , 1989, Hepato-gastroenterology.

[23]  W. Schmiegel Tumor markers in pancreatic cancer--current concepts. , 1989, Hepato-gastroenterology.

[24]  D. Pleskow,et al.  Evaluation of a serologic marker, CA19-9, in the diagnosis of pancreatic cancer. , 1989, Annals of internal medicine.

[25]  T. Hayakawa,et al.  Sensitive serum markers for detecting pancreatic cancer , 1988, Cancer.

[26]  T. Yoshikawa,et al.  Elevated serum CA19-9 levels in poorly controlled diabetic patients. , 1986, Japanese journal of medicine.