Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer

doi:10.1053/gast.2001.27210

Gastroenterology

Volume 121, Issue 3, September 2001, Pages 640-645

https://doi.org/10.1053/gast.2001.27210 Get rights and content

Abstract

Background & Aims: Islet amyloid polypeptide (IAPP) levels are elevated in pancreatic cancer and may be a useful marker of pancreatic cancer–associated diabetes. The aim of this study was to compare the sensitivity and specificity for pancreatic cancer of IAPP with that of CA19-9, examine clinical characteristics of diabetes in pancreatic cancer, and define the relationship of IAPP to diabetes of pancreatic cancer. Methods: Fasting serum glucose, IAPP, and CA 19-9 were measured in 130 subjects with pancreatic cancer, 250 subjects with other pancreatic and peripancreatic diseases, and 116 controls. In pancreatic cancer patients, we noted tumor stage and the presence and duration of diabetes. Results: IAPP was markedly elevated in pancreatic cancer, especially in patients with diabetes. However, the sensitivity of IAPP for pancreatic cancer was less than that of CA 19-9 (40% vs. 75%; P < 0.001). Diabetes was present in 46% of pancreatic cancers and 55% of resectable tumors. In pancreatic cancer with diabetes, the sensitivity of IAPP was only 50%. In resectable cancer it was 27%. Conclusions: IAPP is elevated in pancreatic cancer but is not sensitive enough to replace or complement existing tests. Diabetes occurs early and frequently in pancreatic cancer. Development of a sensitive and specific marker for pancreatic-associated diabetes might lead to diagnosis of resectable pancreatic cancer.

GASTROENTEROLOGY 2001;121:640-645

Section snippets

Materials and methods

After the protocol was approved by the Institutional Review Board and written informed consent was obtained from all participants in the study, 496 pancreas clinic patients were prospectively enrolled into the study (Table 1).

. Final diagnoses in the 496 patients studied

Final diagnosis	No. of patients
Pancreatic cancer	130
Acute and chronic pancreatitis	169
Benign pancreatic tumors	19
Islet cell tumors	9
Lymphoma	8
Benign pancreatic cysts	9
Bile duct and ampullary tumors	25
Bile duct stones	4
Nonpancreatic cancer	7

IAPP

The mean plasma concentration of IAPP in patients with pancreatic cancer was 9.8 ± 0.7 pmol/L. This was significantly higher (P < 0.001) than the IAPP levels in all other patient groups (Figure 1).

. Scatter diagram of serum IAPP in patient groups. “Others” includes bile duct and ampulary tumors, cysts, and benign pancreatic tumors. The line represents the cutoff value for IAPP used in the study. *P ≤ 0.001 vs. all other groups. AP, acute pancreatitis; CP, chronic pancreatitis; PC, pancreatic

Discussion

The study by Permert et al.¹ reporting elevated levels of IAPP in pancreatic cancer generated an exciting hypothesis that IAPP may be a valuable marker for detection of early pancreatic cancer. This study had only 30 subjects with pancreatic cancer. In our study of nearly 500 patients with a variety of pancreatic and peripancreatic diseases and controls, we conclusively show that IAPP is not a satisfactory marker for pancreatic cancer. It is far less sensitive than CA 19-9 for detection of

References (17)

X Ding et al.
Pancreatic cancer cells selectively stimulate islet beta cells to secrete amylin
Gastroenterology
(1998)
J Permert et al.
Islet amyloid polypeptide in patients with pancreatic cancer and diabetes
N Engl J Med
(1994)
J Permert et al.
Pancreatic cancer is associated with impaired glucose metabolism
Eur J Surg
(1993)
J Permert et al.
Diagnosis of pancreatic cancer. Alteration of glucose metabolism
Int J Pancreatol
(1991)
E Cersosimo et al.
Insulin secretion and action in patients with pancreatic cancer
Cancer
(1991)
J Permert et al.
Improved glucose metabolism after subtotal pancreatectomy for pancreatic cancer
Br J Surg
(1993)
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
Diabetes Care
(1997)
J Permert et al.
Islet hormone secretion in pancreatic cancer patients with diabetes
Pancreas
(1997)

There are more references available in the full text version of this article.

Cited by (75)

Hemoglobin A1c as a marker to stratify diabetes risk following pancreaticoduodenectomy
2020, Surgery Open Science
Pancreatic cancer has been shown to cause diabetes mellitus, and diabetes mellitus has been shown to be a risk factor for pancreatic cancer. The effect of pancreaticoduodenectomy on risk for development of diabetes mellitus is unclear. This study used hemoglobin A1c to determine the incidence of diabetes mellitus development following pancreaticoduodenectomy based on preoperative risk of diabetes mellitus.
Retrospective review of patients undergoing pancreaticoduodenectomy was performed with comparison of preoperative diabetes mellitus status and hemoglobin A1c with development of diabetes mellitus postoperatively. Risk ratios were calculated to determine the risk for diabetes mellitus development.
Among 90 patients who met inclusion criteria, 26.7% developed new-onset or worsening diabetes mellitus following pancreaticoduodenectomy. Of those with hemoglobin A1c ≤ 5.6%, only 7.7% of patients developed diabetes mellitus. Patients at risk for diabetes mellitus preoperatively had 4.0 times greater risk for development of diabetes mellitus following pancreaticoduodenectomy.
Hemoglobin A1c levels should be used to identify patients at risk for new-onset or worsening diabetes mellitus following pancreaticoduodenectomy.
Contribution of biomarkers for pancreatic cancer-associated new-onset diabetes to pancreatic cancer screening
2018, Pathology Research and Practice
Pancreatic cancer (PaC) is one of the deadliest types of tumor, and it is regarded as a fatal disease, with a 5-year survival rate less than 10%. Most clinical diagnoses for PaC are made at an advanced stage because of the insidious onset of the disease, which leads to an extremely poor prognosis.
The relationship between diabetes mellitus (DM) and PaC has been established by several decades of research, and the prevalence of DM in patients with PaC has been reported to be 40%, with half of the patients having developed new-onset DM within 2 years or less. Increasing evidence suggests that new-onset DM is associated with a high prevalence of PaC, and PaC resection ameliorates DM. Therefore, screening for PaC may be needed in patients with newly developed DM.
The objective of this review was to present our current understanding of biomarkers for PaC-associated new-onset DM (PCAND), to offer a perspective on the prospects and problems of using this strategy for early screening to differentiate PCAND from new-onset type 2 DM not associated with PaC and to suggest candidate biomarkers to use for PaC screening in patients with new-onset DM. Finding sensitive and specific biomarkers to manage these patients constitutes a challenge for the research community and for public health policies.
Model to Determine Risk of Pancreatic Cancer in Patients With New-Onset Diabetes
2018, Gastroenterology
Of patients with new-onset diabetes (NOD; based on glycemic status) older than 50 years, approximately 1% are diagnosed with pancreatic cancer (PC) within 3 years. We aimed to develop and validate a model to determine risk of PC in patients with NOD.
We retrospectively collected data from 4 independent and nonoverlapping cohorts of patients (N = 1,561) with NOD (based on glycemic status; data collected at date of diagnosis and 12 months previously) in the Rochester Epidemiology Project from January 1, 2000 through December 31, 2015 to create our model. The model weighed scores for 3 factors identified in the discovery cohort to be most strongly associated with PC (64 patients with PC and 192 with type 2 diabetes): change in weight, change in blood glucose, and age at onset of diabetes. We called our model Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC). We validated the locked-down model and cutoff score in an independent population-based cohort of 1,096 patients with diabetes; of these, 9 patients (82%) had PC within 3 years of meeting the criteria for NOD.
In the discovery cohort, the END-PAC model identified patients who developed PC within 3 years of diabetes onset (area under receiver operating characteristic curve 0.87); a score of at least 3 identified patients who developed PC with 80% sensitivity and specificity. In the validation cohort, a score of at least 3 identified 7 of 9 patients with PC (78%) with 85% specificity; the prevalence of PC in patients with a score of at least 3 (3.6%) was 4.4-fold greater than in patients with NOD. A high END-PAC score in patients who did not have PC (false positives) was often due to such factors as recent steroid use or different malignancy. An ENDPAC score no higher than 0 (in 49% of patients) meant that patients had an extremely low risk for PC. An END-PAC score of at least 3 identified 75% of patients in the discovery cohort more than 6 months before a diagnosis of PC.
Based on change in weight, change in blood glucose, and age at onset of diabetes, we developed and validated a model to determine risk of PC in patients with NOD based on glycemic status (END-PAC model). An independent prospective study is needed to further validate this model, which could contribute to early detection of PC.
Chiroptical spectroscopy and metabolomics for blood-based sensing of pancreatic cancer
2018, Chirality
To enable the early diagnosis of pancreatic cancer, the search for and definition of reliable biomarkers remain a subject of great interest, with the specificity and sensitivity of the currently used biomarkers being below the required values. We tested a novel diagnostic approach for pancreatic cancer based on the specific molecular signature of blood plasma components. To acquire more detailed structural information, structure‐sensitive chiroptical methods (electronic circular dichroism and Raman optical activity) were supplemented by conventional Raman and infrared spectroscopies. The obtained spectra were subsequently processed by linear discriminant analysis yielding high values of specificity and sensitivity. In addition, to monitor not only large biomolecules as potential biomarkers but also those of low molecular weight, we conducted an analysis of blood plasma samples by using metabolomics. The achieved results suggest a panel of promising biomarkers for a reliable detection of pancreatic cancer.
Diabetes mellitus in intraductal papillary mucinous neoplasm of the pancreas is associated with high-grade dysplasia and invasive carcinoma
2017, Pancreatology
Citation Excerpt :
However, very limited attention has been paid to the role of metabolic risk factors in the malignant progression of IPMN. Diabetes mellitus (DM) is a frequent finding in patients with pancreatic ductal adenocarcinoma (PDAC) and a wealth of epidemiological evidence indicates that new-onset DM is strongly associated with a PDAC diagnosis [3–10]. Whether DM is associated with malignant progression of IPMN is not well established, and only a few studies have reported associations between DM and degree of dysplasia in IPMN with conflicting results [11–18].
While the association between Diabetes Mellitus (DM) and pancreatic ductal adenocarcinoma is well recognized, its importance in intraductal papillary mucinous neoplasm of the pancreas (IPMN) is not well-defined. We sought to examine the associations of DM with degree of dysplasia and morphological subtypes in IPMN.
In 454 patients with resected IPMN, we evaluated associations of DM with high-grade dysplasia (HGD), invasive carcinoma, precursor epithelial subtype (gastric, intestinal, oncocytic, pancreatobiliary), and histological type of invasive carcinomas (tubular, colloid, oncocytic) using logistic regression. We performed multivariate analyses adjusting for worrisome features and high-risk stigmata of malignancy in a subset of 289 patients with annotated radiological characteristics.
The prevalence of DM in our study was 34%. DM was significantly associated with HGD (OR 2.02, 95% CI 1.02–4.01, P = 0.045) and invasive carcinoma (OR 2.05, 95% CI 1.08–3.87, P = 0.027) after adjusting for worrisome features. Compared to patients without DM, those with recent-onset DM (≤5 years before surgery) had 6.9-fold (95% CI 2.38–19.92, P < 0.001) higher risk of invasive carcinoma. DM was associated with increased likelihood of intestinal-type precursor epithelium (OR 1.63, 95% CI 1.07–2.47, P = 0.022) and colloid carcinomas (OR 2.46, 95% CI 1.01–5.99, P = 0.047)
Preoperative DM was associated with significantly higher risk of HGD and invasive carcinoma in resected IPMN, and risk of invasive carcinoma was highest in patients with recent-onset DM. Patients with DM were more likely to harbor intestinal-type IPMN and colloid carcinomas. Our findings suggest that a diagnosis of DM in patients with IPMN may warrant more aggressive surveillance.
Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer
2016, The Lancet Gastroenterology and Hepatology
Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps.

View all citing articles on Scopus

^☆: Address requests for reprints to: Suresh T. Chari, M.D., 200 First Street SW, Mayo Clinic, Rochester, Minnesota 55905. e-mail: [email protected]; fax: (507) 284-5486.

View full text

Liver, Pancreas, and Biliary TractIslet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer☆

Abstract

Section snippets

Materials and methods

IAPP

Discussion

Gastroenterology

Islet amyloid polypeptide in patients with pancreatic cancer and diabetes

N Engl J Med

Pancreatic cancer is associated with impaired glucose metabolism

Eur J Surg

Diagnosis of pancreatic cancer. Alteration of glucose metabolism

Int J Pancreatol

Insulin secretion and action in patients with pancreatic cancer

Cancer

Improved glucose metabolism after subtotal pancreatectomy for pancreatic cancer

Br J Surg

Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus

Diabetes Care

Islet hormone secretion in pancreatic cancer patients with diabetes

Pancreas

Liver, Pancreas, and Biliary Tract
Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer☆