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Predictors for Pancreatic Cancer Diagnosis Following New-Onset Diabetes Mellitus.

ABSTRACT: New-onset diabetes mellitus (NODM) in adults is often an early manifestation of pancreatic cancer (PaCa), but the incidence of PaCa in this cohort is rather low. We evaluated whether combining other patient factors such as age, smoking history, the absence of obesity, the presence of chronic pancreatitis (CP), and gallstone disease can result in a more enriched cohort.After a washout period of 2 years to exclude pre-existing PaCa or DM, 507,378 non-diabetic patients in the veterans' administration healthcare system were identified. Patients <40 years (n=54,465) and those with PaCa diagnosed before the diagnosis of diabetes (n=22) were excluded. A total of 452,804 veterans were followed for development of DM or PaCa.73,811 patients (16.3%) developed NODM during the follow-up period. One hundred and eighty-three NODM patients (0.25%) were diagnosed with PaCa within 3 years. In comparison, 434 of 378,993 remaining patients (0.11%) developed PaCa in 3 years following inclusion into the study [relative risk (RR)=2.27, 95% confidence intervals (CI) 1.96, 2.63; P<0.0001]. The risk of PaCa diagnosis was higher among patients who were non-obese (RR=1.51), were ≥65 years old (RR=2.01), were heavy smokers (RR=1.55), and had a history of CP (RR=4.72) or gallstone disease (RR=2.02). Using a combination of these risk factors in NODM patients resulted in up to 0.72% three-year risk of PaCa but captured only 17% of patients with PaCa.Based on our findings, the likelihood of PaCa in adults with NODM even after adjusting for other potential risk factors for PaCa including age, body mass index, smoking, gallstones, and CP is probably not high enough to recommend routine evaluation for all these patients for underlying PaCa.

SUBMITTER: Munigala S

PROVIDER: S-EPMC4816040 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:BackgroundThe lack of specific predictors for type-2 diabetes mellitus (T2DM) severely impacts early intervention/prevention efforts. Elevated branched-chain amino acids (BCAAs: Isoleucine, leucine, valine) and aromatic amino acids (AAAs: Tyrosine, tryptophan, phenylalanine)) show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies. However, improvement is needed to support its clinical utility.AimTo evaluate the effects of body mass index (BMI) and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.MethodsNinety-seven new-onset T2DM patients (< 12 mo) differing in BMI [normal weight (NW), n = 33, BMI = 22.23 ± 1.60; overweight, n = 42, BMI = 25.9 ± 1.07; obesity (OB), n = 22, BMI = 31.23 ± 2.31] from the First People's Hospital of Yunnan Province, Kunming, China, were studied. One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.ResultsFasting serum AAAs, BCAAs, glutamate, and alanine were greater and high-density lipoprotein (HDL) was lower (P < 0.05, each) in OB-T2DM patients than in NW-T2DM patients, especially in male OB-T2DM patients. Arginine, histidine, leucine, methionine, and lysine were greater in male patients than in female patients. Moreover, histidine, alanine, glutamate, lysine, valine, methionine, leucine, isoleucine, tyrosine, phenylalanine, and tryptophan were significantly correlated with abdominal adiposity, body weight and BMI, whereas isoleucine, leucine and phenylalanine were negatively correlated with HDL.ConclusionHeterogeneously elevated amino acids, especially BCAAs/AAAs, across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development. The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals, whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals. This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

Project description:BACKGROUND & AIMS: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

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Predictors for Pancreatic Cancer Diagnosis Following New-Onset Diabetes Mellitus.

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