Diabetes and Pancreatic Cancer
Diabetes and Pancreatic Cancer
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: Diabetes mellitus occurs commonly in pancreatic cancer patients. In an analysis of 512 newly diagnosed cases, almost 50% met criteria for DM. In the great majority of cases, the DM developed within two years of the diagnosis of pancreatic cancer. Patients with both DM and PaC could not be differentiated on the basis of tumor size or clinical stage.
Source: Pannala R, et al. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology. 2008;134:981-987.
Pancreatic cancer (PaC) remains the fourth leading cause of cancer death in the United States1 and currently the only key to long-term survival is early recognition and surgical excision. It has long been recognized that diabetes mellitus (DM) is common among patients with pancreatic cancer, occurring in approximately 50% of cases.2,3 DM associated with PaC is typically of recent onset and often not to be associated with known risk factors, such as family history and obesity.
To examine this association of PaC and DM and to assess if there were features of the DM that are specific to PaC in contrast to the typical type II DM, Pannala and colleagues from the Mayo Clinic prospectively recruited 512 newly diagnosed PaC cases and 933 controls of similar age, who then completed demographic and clinical questionnaires and had fasting blood glucose (FBG) levels measured. FBG levels were also obtained after surgery for the 105 patients who had pancreaticoduodenectomy (n = 105). Subjects with a FBG level >126 mg/dL or who were on antidiabetic treatment were classified as having DM.
Compared to controls, DM was more prevalent in PaC patients (47% vs 7%; P < .001), and more likely to be of new onset (< 2-year duration) (74% vs 53%; P = .002). Among PaC cases, those with DM (n = 243) were older (68 ± 10 vs 64 ± 12 years; P < .001), reported higher usual adult body mass index (30 ± 6 vs 27 ± 5 kg/m2; P < .001), and had a greater frequency of family history of DM (47% vs 31%; P < .001) compared with those without DM (n = 269). After pancreaticoduodenectomy, while DM resolved in 17 of 30 patients (57%) with new-onset DM, its prevalence was unchanged in patients with long-standing DM (n = 11) (P = .009).
Thus, PaC should be considered a powerful diabetogenic state. In this prospective study of 512 cases (and 933 controls) nearly half of the patients met criteria for DM, and this was frequently of recent onset (< 2 years). This high prevalence raises the question of whether newly discovered DM is sufficient to warrant a search for early pancreatic cancer in otherwise asymptomatic adults. In fact, one study found that approximately 1% of newly-diagnosed diabetic subjects aged 50 years or older will be diagnosed with pancreatic cancer within three years.4 When DM develops in a person without known risk factors, suspicion might be heightened, but it is notable that in this series a significant portion of the newly developed DM occurred in patients with a positive DM family history.
That the association of PaC and DM occurs has long been recognized; however the pathophysiology is unclear. In this regard the current report gives some direction. One possibility is that the neoplastic process destroys functioning insulin-secreting beta cells. However, if this were the case, it would be expected that PaC associated with DM would be expected to be more advanced. In the current report, there was no difference in image-derived estimates of tumor size or clinical stage in those PaC patients without DM. Furthermore, others have shown that insulin and C-peptide levels are high in patients with DM associated Pa-C; typical of what one would expect in type II DM, but not if the DM had occurred as a result of pancreatic tissue destruction.5,6
Alternatively, the evolving neoplastic process may somehow promote a condition of insulin resistance akin to type II DM. This would be consistent with elevated insulin levels, as noted above, and also with the postoperative findings described in this report. Of the 30 patients with new-onset DM and PaC, 17 had resolution of their diabetes after tumor excision. This striking finding suggests that the pancreatic cancer itself influences glucose regulation through a yet-to-be described mechanism. The authors speculate that a tumor-secreted factor may be involved, but currently there is limited supporting data for this hypothesis.
By whatever mechanism, the high prevalence of glucose intolerance in pancreatic cancer patients is important for managing oncologists treating pancreatic cancer patients. Primary physicians should be aware that the new onset of DM in adults should trigger consideration of the possibility of the presence of early resectable pancreatic cancer. Further work is needed to discern the mechanism of PaC-associated DM and if distinct tumor produced soluble mediators are discovered, these should be examined in the context of early diagnosis and treatment.
1. Jemal A, et al. Cancer statistics, 2007. CA Cancer J Clin. 2007;57(1):43-66.
2. Noy A, Bilezikian JP. Clinical review 63: Diabetes and pancreatic cancer: clues to the early diagnosis of pancreatic malignancy. J Clin Endocrinol Metab. 1994;79(5):1223-1231.
3. Permert J, et al. Pancreatic cancer is associated with impaired glucose metabolism. Eur J Surg. 1993;159(2):101-107.
4. Chari ST, et al. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology. 2005;129(2):504-511.
5. Permert J, et al. Islet hormone secretion in pancreatic cancer patients with diabetes. Pancreas. 1997;15(1):60-68.
6. Permert J, et al. Islet amyloid polypeptide in patients with pancreatic cancer and diabetes. N Engl J Med. 1994;330(5):313-318.Patients with both DM and PaC could not be differentiated on the basis of tumor size or clinical stage.
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