We searched Pubmed and Ovid databases using combinations of the following key words: “diabetes”, “pancreatic cancer”, and “screening”, and retrieved articles from 1985 through to the present. Only English-language studies were considered. All authors reviewed original studies and reviews for relevance and included all pertinent studies in the preparation of the manuscript. We also reviewed the bibliographies of the selected articles for other pertinent citations.
Personal ViewNew-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer
Introduction
A screening strategy for sporadic pancreatic cancer has not been established. In view of the fact that pancreatic-cancer-specific symptoms occur late in the course of the disease, early detection will require screening of asymptomatic individuals. Pancreatic cancer is a markedly diabetogenic state and there is increasing evidence that diabetes is prevalent even in early-stage, asymptomatic pancreatic cancer. The objective of this review is to present our current understanding of pancreatic-cancer-associated diabetes and offer a perspective on the prospects and issues of using this strategy for early detection of pancreatic cancer.
Section snippets
The need for early detection of pancreatic cancer
Pancreatic cancer is the fourth leading cause of cancer death in the USA1 and the fifth leading cause of cancer death in Europe.2 It has a dismal 5-year survival of about 5%,3 mainly due to the fact that disease-specific symptoms occur late in the course of the disease; at the time of diagnosis, 50% of patients have distant metastases, 29% have local or regional spread, and only 3% have tumours confined to the pancreas (19% remain unstaged or unknown).4 By the time of diagnosis, less than 15%
Opportunities to detect resectable pancreatic cancer
Invasive pancreatic cancer develops from precancerous non-invasive precursor lesions called pancreatic intraepithelial neoplasia (PanIN), which progress from PanIN1 through to PanIN3 (carcinoma in situ).11 The timeline of the progression of pancreatic cancer is not well established. In a case series, Brat and colleagues reported the presence of PanINs 17 months to 10 years before the clinical diagnosis of cancer.12 To understand better the timeline of progression of pancreatic cancer, we
Challenges of screening for asymptomatic pancreatic cancer
The detection of early pancreatic cancer will require screening of asymptomatic patients for the disease. However, two major obstacles restrict our ability to screen for pancreatic cancer: an absence of a high-risk group of patients and an absence of sensitive and specific marker(s) of early pancreatic cancer. However, even if a biomarker with very high sensitivity and specificity is identified, screening the general population for asymptomatic pancreatic cancer is unlikely to be cost effective
Diabetes and pancreatic cancer: what is the relation?
A review of studies assessing the association between diabetes and pancreatic cancer suggests that, although long-standing diabetes is an aetiological factor for pancreatic cancer, new-onset diabetes is its manifestation. There is a modestly increased risk of pancreatic cancer in people with long-standing diabetes.20 A recent meta-analysis of 17 case–control and 19 cohort (or nested case–control) studies published between 1966 and 2005 noted that the combined age-adjusted and sex-adjusted odds
Diabetes caused by pancreatic cancer
Patients with pancreatic cancer often have new-onset diabetes, which resolves with cancer resection, as noted in a case study shown in figure 2. Here we review the clinical and experimental evidence that supports the notion that pancreatic cancer causes diabetes.
New-onset diabetes: a potential first filter for pancreatic-cancer screening
Patients with new-onset diabetes have a higher probability than the general population of subsequently being diagnosed with pancreatic cancer. In a population-based cohort of 2122 diabetic individuals in Olmsted County, MN, USA, we noted that 18 (0·8%) individuals with new-onset diabetes, who were aged 50 years or older, were diagnosed with pancreatic cancer within 3 years of meeting criteria for diabetes and the observed-to-expected ratio of pancreatic cancer in this cohort of newly diagnosed
Proposed screening strategy based on new-onset diabetes
We propose that asymptomatic individuals be screened for diabetes and those with new-onset diabetes undergo secondary filtering to further enrich the group for pancreatic-cancer detection. This cohort would then undergo non-invasive imaging or endoscopic ultrasonography to identify and confirm the diagnosis of pancreatic cancer (figure 4).
About half of patients with sporadic pancreatic cancer have diabetes. In nearly 50% of these patients, the diabetes is diagnosed concomitant with, or shortly
Pathogenesis of pancreatic-cancer-associated diabetes
Diabetes is caused by a relative or absolute impairment in insulin secretion (β-cell dysfunction) along with varying degrees of peripheral resistance to insulin action (insulin resistance).49, 50 Although insulin resistance is frequently noted in several physiological and pathological states, including puberty, pregnancy, ageing, and obesity, most insulin-resistant individuals do not develop hyperglycaemia, because normal pancreatic islet cells compensate for impaired insulin action by
Conclusion
Early detection of pancreatic cancer seems to hold the greatest promise with regards to improving long-term survival. For this, screening will need to be targeted at asymptomatic individuals. New-onset diabetes is present in almost half of all patients with pancreatic cancer and various lines of evidence suggest that the diabetes is caused by the cancer. Importantly, diabetes seems to be associated with early-stage pancreatic cancer. However, further enrichment of the population of patients
Search strategy and selection criteria
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