Diabetes In Pancreatic Cancer Research Articles

Association between pancreatic cancer and diabetes: insights from a retrospective cohort study

BackgroundStudies investigating the prevalence of pancreatic cancer have revealed a heightened risk of 1.5 to 2.0 times among individuals with long-standing type 2 diabetes mellitus.AimsWe aimed to estimate the prevalence of diabetes among patients with pancreatic cancer, and identify the factors associated with type 2 diabetes mellitus in this population.MethodsThis retrospective observational and analytical study was carried out in the Department of Gastroenterology of the Mohammed VI University Hospital over a period of 5 years, between 2018 and 2022, including all patients with confirmed cases of pancreatic adenocarcinoma.ResultsOut of the 197 patients, 38.1% had a history of diabetes, among them, 42.7% had new-onset diabetes, while the remaining 57.3% had long-standing diabetes. Diabetic patients were significantly older than nondiabetic patients (mean age of 67.2 vs. 63, P = 0.009). Diabetes was more prevalent among obese patients (66.7%, P = 0.01), and less frequent among individuals with chronic alcohol consumption (20% vs. 80%, P = 0.04), and tobacco smokers (24.4% vs75.6%, P = 0.03). Among patients with an ECOG score ≥ 3, DM, 54.5% were DM-patients (P = 0.033). The same significant association was found for the Nutritional Risk Index, Patients who had moderate or severe malnutrition were more likely to be diabetic 74.7% (P = 0.004). Diabetic patients were less likely to undergo surgery due to comorbidities and general health deterioration. However, no significant differences were observed in sex, tumor stage or location.ConclusionOur study has shown an increased prevalence of diabetes in pancreatic cancer and highlights the importance of considering this cancer in cases of recent onset or uncontrolled diabetes, especially in elderly individuals.

The Role of Type 2 Diabetes in Pancreatic Cancer.

The incidence of type 2 diabetes mellitus (T2DM) and its potential complications, such as cancers, are increasing worldwide at an astounding rate. There are many factors such as obesity, diabetes, alcohol consumption, and the adoption of sedentary lifestyles that are driving pancreatic cancer (PC) to become one of the leading causes of cancer mortality in the United States. PC is notorious for its generic symptoms and late-stage presentation with rapid metastasis. The connection between T2DM and the risk of PC development is multifaceted and complex. Some of the proposed theories reveal that chronic inflammation, insulin resistance, hyperinsulinemia, hyperglycemia, and abnormalities in the insulin and insulin-like growth factor axis (IGF) contribute to the disease association between these two conditions. This literature review aims to highlight relevant studies and explore the molecular mechanisms involved in the etiology of diabetes and its impact on PC development, as well as the role of anti-diabetic agents on PC. Despite extensive studies, the exact interaction between T2DM and PC remains obscure and will need further investigation. According to current knowledge, there is a substantial link between diabetes, obesity, and dietary patterns in the development and progression of PC. Consequently, focusing our efforts on preventive measures by reducing modifiable risk factors remains the most effective strategy to reduce the risk of PC at this time. Antidiabetic drugs can have various effects on the occurrence and prognosis of PC with metformin offering a clear benefit of inhibiting PC and insulin increasing the risk of PC. The development of future novel therapies will require a deeper knowledge of the triggering mechanisms and interplay between these two disease states.

Temporal patterns of new-onset diabetes in pancreatic cancer

Temporal patterns of new-onset diabetes in pancreatic cancer

Diabetes mellitus and pre-diabetes are frequently undiagnosed and underreported in patients referred for pancreatic surgery. A prospective observational study

ObjectivePrevious reports on the prevalence of diabetes in pancreatic cancer and chronic pancreatitis patients are based on inconsistent and equivocal criteria. The objective of this study is to prospectively assess with conclusive methods the preoperative glycaemic status of patients undergoing pancreatic surgery. We hypothesise that most of those patients are unaware of these disturbances in glycaemic status and that the prevalence is underestimated. MethodsDuring the last 2 years, patients referred for pancreatic surgery and without history of diabetes underwent a prospective preoperative screening with an oral glucose tolerance test (OGTT) and determination of the glycated haemoglobin level (HbA1c). The American Diabetes Association's criteria for diabetes and pre-diabetes were used. Beta-cell function and insulin sensitivity were calculated using HOMA2 indices. Impact on surgical policy has been scored. Results99 patients were screened, 25 had a history of diabetes. The other 74 underwent an OGTT and HbA1c determination. Only 29.7% (22/74) had a normal glucose metabolism, while 8.1% (6/74) had impaired fasting glucose, 21.6% (16/74) had impaired glucose tolerance, 6.7% (5/74) had a combination of both, and 33.8% (25/74) had undiagnosed diabetes. In 15.2% (15/99) of the patients, this preoperative assessment had an impact on surgical policy. Conclusions77.7% of patients referred for pancreatic surgery had some degree of (pre-)diabetes. In 70.3% of patients without a history of diabetes, these disturbances in glucose metabolism are a new finding. Physicians involved in pancreatic surgery should be aware of the frequently undiagnosed (pre-)diabetes and actively check for it. This prevalence is underestimated.

Pathogenesis of pancreatic cancer exosome-induced lipolysis in adipose tissue

Background and objectivesNew-onset diabetes and concomitant weight loss occurring several months before the clinical presentation of pancreatic cancer (PC) appear to be paraneoplastic phenomena caused by tumour-secreted products. Our recent...

New-onset Diabetes: A Clue to the Early Diagnosis of Pancreatic Cancer

Pancreatic cancer is the tenth most common cancer diagnosis; however, it is the fourth most common cause of death due to cancer. Recent estimates suggest that by 2020 pancreatic cancer will become the second most common cause of cancer death in the US. The 5-year survival rate in all patients is only ~5% and has not changed significantly over the past five decades. Though the relationship between diabetes mellitus and pancreatic cancer has been known for over 125 years, it still remains to be fully understood. The complex relationship between the two diseases has been the subject of numerous clinical, epidemiological, laboratory and experimental studies. Epidemiologic studies suggest that long-standing type 2 diabetes is a modest risk factor for the development of pancreatic cancer. Meta-analysis of multiple cohort and case-control studies show that the risk of pancreatic cancer in those with diabetes for >5 years is 1.5 to 2.0 fold higher. This s not fully explained by shared risk factors between the two diseases such as obesity. There is also strong clinical, epidemiological and experimental evidence to show that pancreatic cancer causes diabetes. Hyperglycemia and diabetes mellitus occur in ~85% of pancreatic cancer subjects, with diabetes being present in 45% to 67% of pancreatic cancer patients depending on how diabetes is ascertained. Majority (~75%) of diabetes in pancreatic cancer is new-onset, i.e., less than 3 years in duration. The new-onset diabetes often resolves with resection of cancer. The notion that new-onset diabetes in pancreatic cancer is a paraneoplastic phenomenon caused by tumor secreted products was strengthened by a recent study that proposed adrenomedullin, a 52 amino-acid polypeptide, as a strong candidate for mediator of diabetes in pancreatic cancer. In previous studies adrenomedullin has been shown not only to promote pancreatic cancer aggressiveness, but also inhibits insulin exocytosis from beta cells. In the aforementioned study pancreatic cancer cell lines overexpressing adrenomedullin were shown to inhibit insulin secretion, an effect that was reversed by silencing adrenomedullin. Adrenomedullin was also shown to be overexpressed in human pancreatic cancer and plasma levels of adrenomedullin were also increased in pancreatic cancer patients, especially those with diabetes. New-onset diabetes appears to be the only clue to the presence of asymptomatic sporadic pancreatic cancer. Nearly 25% of patients with pancreatic cancer are diagnosed with diabetes 6 months to 36 months before the diagnosis of pancreatic cancer. Conversely, subjects with new-onset diabetes over age 50 years have an 8-fold higher risk for having pancreatic cancer. Thus new-onset diabetes may be a clue to the early diagnosis of the cancer. However, the success of the strategy to use new-onset diabetes as a marker of pancreatic cancer will depend on our ability to distinguish pancreatic cancer-associate diabetes from the more common type 2 diabetes. This strategy provides for diagnosis of early, asymptomatic pancreatic cancer. Image: Determination of the three-dimensional structure of adrenomedullin, a first step towards the analysis of its interactions with receptors and small molecules (from NCBI Structure ).

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium

Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

The American Pancreatic Association/Hirshberg Foundation Symposium Celebrating the 10th Anniversary of the Seed Grant Program

The Hirshberg Foundation for Pancreatic Cancer Research was founded by Agi Hirshberg in 1997, following her husband Ronald Hirshberg’s 8-month, 7-day battle with the disease. (http://www.pancreatic.org/). At the time, the Hirshberg family viewed pancreatic cancer as the ‘‘unknown enemy’’ (http:// www.pancreatic.org/site/c.htJYJ8MPIwE/b.8276835/k.66CB/ Agi_Hirshbergs_Story.htm). In the years since Ronald Hirshberg’s death, Agi Hirshberg has made it her mission to unmask the unknown for others facing the same enemy. When patients present with a new diagnosis of pancreatic cancer, most are already in an advanced stage of the disease. Pancreatic cancer is resistant to most chemotherapeutic agents and radiotherapy. These factors combine to make pancreatic cancer a highly lethal disease, and according to the National Cancer Institute (NCI) 2013 estimates, pancreatic cancer was diagnosed in approximately 45,220 US citizens, and some 38,460 died of the disease. 1 The Annual Report to the Nation on the Status of Cancer, 1975Y2009, shows that overall cancer death rates continued to decline in the United States among both men and women, among all major racial and ethnic groups, and for all of the many common cancer sites, including lung, colon and rectum, female breast, and prostate. However, this trend does not hold true for pancreatic cancer. The report demonstrates that death rates continued to increase during the latest time period (2000 through 2009) for pancreatic cancer. 2 Only about 23% of patients with cancer of the pancreas will still be living 1 year after diagnosis, and only about 4% will survive 5 years. Even for those diagnosed with pancreatic cancer that has not spread to other organs or systems, the overall 5-year survival rate approaches only 15%. The Hirshberg Foundation’s vision is to advance pancreatic cancer research and provide information, resources, and support to pancreatic cancer patients and their families. The mission of the Foundation is as follows: & To find a cure for pancreatic cancer in honor of Ron Hirshberg and the thousands of people who are diagnosed with this disease each year. & To create a premier Pancreatic Cancer Center where all needs of pancreatic cancer patients can be met in one location with the most advanced treatment options. & To be recognized as a patient support reference source for

Mo1415 Diabetes in Pancreatic Cancer Is Associated With Preferential Loss of Subcutaneous Over Visceral Fat

Mo1415 Diabetes in Pancreatic Cancer Is Associated With Preferential Loss of Subcutaneous Over Visceral Fat

New-onset diabetes in pancreatic cancer: A study in the primary care setting

BackgroundOnset of diabetes mellitus (DM) is often first noted by primary care physicians. New-onset DM (duration <36 months before PaC diagnosis) can be a harbinger of pancreatic cancer (PaC). However, its clinical significance remains unclear. MethodsTo determine the prevalence, onset, and delay in diagnosis of DM in PaC patients in the primary care setting, we retrospectively reviewed the records of consecutive patients followed in Mayo Clinic’s primary care clinics (at least one visit in the preceding 2 years) from 1995 to 2009 who were eventually diagnosed with PaC. Onset of DM was the first date the fasting blood glucose was ≥126 mg/dl. ResultsOf the 111 PaC patients (59 male, median age 74 years), 52 (47%) had DM of whom 30 (58%) had new-onset DM. Among the 30 with new-onset DM, 24 (80%) were asymptomatic (no cancer-specific symptoms), at DM onset. In these 24 patients, median duration of DM prior to PaC diagnosis was 6.5 (0.5–35) months, and median delay between onset and physician diagnosis of DM was 2.5 (0.25–14) months, which decreased from 8.8 (3.5–14) months in patients with DM onset between 1995 and 1999 to 0 (0–2) months, in patients with DM onset between 2004 and 2009. However, the proportion of patients with undiagnosed DM (∼33%) remained unchanged. ConclusionsDiabetes is very common (∼50%) in PaC. In over a fifth of PaC, the onset of DM occurs when the cancer is asymptomatic, providing a potential window-of-opportunity to diagnose early PaC. However, nearly a third of new-onset DM in PaC remains undiagnosed.

Morphometric studies in human pancreatic cancer argues against the etiological role of type 2 diabetes in pancreatic cancer.

To understand the role of islet amyloid polypeptide (IAPP) in type 2 diabetes and pancreatic cancer (PC), we investigated the patterns of its expression and its ratio to insulin, glucagon, somatostatin and pancreatic polypeptide cells by morphometry in tissues from these two diseases in comparison to the normal pancreas. Pancreatic tissues from 11 donors (five without pancreatic disease and six with type 2 diabetes) and 11 surgical specimens from PC patients obtained from the cancer area (zone A) and the adjacent tumor-free area (zone B) were examined immunohistochemically. The size of islets, the number on beta-, alpha-, delta- pp- and IAPP-expressing cells and their ratios in the islets of these tissues were determined. In the normal pancreas, only 50% of the beta-cells while alpha- and delta-cells co-expressed IAPP only sporadically. In tissues from diabetics as well as in zone A, the number of the beta-cells and the IAPP-expressing cells was reduced significantly, while the number of alpha- and delta-cells was increased. In zone B, however, significantly more beta-cell and IAPP-expressing cells and a significantly lower number of alpha-cells were found compared to those in zone A. Significant differences were also found between the specimens from type 2 diabetics and pancreatic cancer relative to the ratios of IAPP/beta-cell, IAPP/alpha-cells and beta-cell/delta-cells. The morphometric data show a decrease rather than an increase in the number of IAPP-expressing cells in PC. Differences in abnormalities in type-2 diabetics and in zone B of PC tissue strongly argue against the role of type 2 diabetes in PC. Rather, the development of diabetes in subjects prone to pancreatic cancer could be a red flag for malignancy.

W1400 Diabetes in Pancreatic Cancer Is Not Mediated By Resistin

W1400 Diabetes in Pancreatic Cancer Is Not Mediated By Resistin

High prevalence of diabetes in patients with pancreatic cancer in central Anatolia, Turkey

Tumor-induced pancreatic damage or insulin resistance may be responsible for diabetes in pancreatic cancer (PC) patients, but the exact cause of association remains controversial. In this study, we aimed to investigate the prevalence of diabetes in patients with PC in central Anatolia, Turkey, and to evaluate whether diabetes is caused by PC. A total of 40 patients with primary PC were enrolled in the study. 13 (32.5%) of the patients had diabetes before PC diagnosis. Oral glucose tolerance test was performed in the remaining 27 patients. The period between the diagnosis of diabetes and detection of PC was less than 1 year in seven (17.5%) patients who had previous diabetes. Recent-onset diabetes and impaired glucose tolerance were detected in 13 (32.5%) and two (5%) of the PC patients, respectively. The prevalence of recent-onset and shortly-before-diagnosed diabetes has been found very high (50%) in our patients with PC. Interestingly, we determined higher levels of insulin and C-peptide in PC patients having abnormal glucose tolerance than patients having normal glucose tolerance. In conclusion, as it has been reported in other population, we determined high prevalence of diabetes in PC patients in central Anatolia. High insulin and C-peptide level indicate that different mechanisms such as insulin resistance may be responsible for abnormal glucose tolerance in PC patients other than the tumor caused insulin deficiency.

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

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

Pancreatic carcinogenicity of N-nitrosobis(2-oxopropyl)-amine in diabetic and non-diabetic Chinese hamsters

To examine the role of diabetes in pancreatic cancer, 4 groups of Chinese hamsters—2 from genetically diabetic and 2 from non-diabetic lines—were treated with N-nitrosobis(2-oxo-propyl)amine (BOP) at different dose levels and intervals. In one group (referred to as the VA group), BOP was given weekly at a 5 mg/kg body wt. level for 18 or 23 weeks, whereas the other group (the EP group) received a weekly dose of 2.5 mg/kg body wt. for life. Except for diet and experimental design, all other laboratory conditions were similar in the two institutions. No VA hamster developed tumors. Three of 22 non-diabetic EP hamsters (but none of the diabetic hamsters) developed pancreatic hyperplastic and neoplastic lesions, comprising ductular cell adenomas (3 hamsters), carcinoma in situ (1 hamster), a well-differentiated adenocarcinoma (1 hamster), and a poorly differentiated adenocarcinoma (1 hamster) with regional lymph node metastases. In addition, over 50% of the EP hamsters had neoplasms for which the incidences and morphology did not vary between diabetic and non-diabetic groups or between the sexes. These were primarily of the liver (cholangiomas), lungs (adenomas) and skin (trichoepitheliomas, squamous cell carcinomas). The differing carcinogenic response of the two hamster groups to BOP apparently is not related to the total BOP dose, but rather to other factors, including the length of observation time.