Dataset Information

Prediction of Pancreatic Cancer in Diabetes Patients with Worsening Glycemic Control.

ABSTRACT:

Background

Worsening glycemic control indicates elevated risk of pancreatic ductal adenocarcinoma (PDAC). We developed prediction models for PDAC among those with worsening glycemic control after diabetes diagnosis.

Methods

In 2000-2016 records within the Veterans Affairs Health System (VA), we identified three cohorts with progression of diabetes: (i) insulin initiation (n = 449,685), (ii) initiation of combination oral hypoglycemic medication (n = 414,460), and (iii) hemoglobin A1c (HbA1c) ≥8% with ≥Δ1% within 15 months (n = 593,401). We computed 12-, 36-, and 60-month incidence of PDAC and developed prediction models separately for males and females, with consideration of >30 demographic, behavioral, clinical, and laboratory variables. Models were selected to optimize Akaike's Information Criterion, and performance for predicting 12-, 36-, and 60-month incident PDAC was evaluated by bootstrap.

Results

Incidence of PDAC was highest for insulin initiators and greater in males than in females. Optimism-corrected c-indices of the models for predicting 36-month incidence of PDAC in the male population were: (i) 0.72, (ii) 0.70, and (iii) 0.71, respectively. Models performed better for predicting 12-month incident PDAC [c-index (i) 0.78, (ii) 0.73, (iii) 0.76 for males], and worse for predicting 60-month incident PDAC [c-index (i) 0.69, (ii) 0.67, (iii) 0.68 for males]. Model performance was lower among females. For subjects whose model-predicted 36-month PDAC risks were ≥1%, the observed incidences were (i) 1.9%, (ii) 2.2%, and (iii) 1.8%.

Conclusions

Sex-specific models for PDAC can estimate risk of PDAC at the time of progression of diabetes.

Impact

Our models can identify diabetes patients who would benefit from PDAC screening.

SUBMITTER: Jeon CY

PROVIDER: S-EPMC8759109 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Prediction of Pancreatic Cancer in Diabetes Patients with Worsening Glycemic Control.

Jeon Christie Y CY Kim Sungjin S Lin Yu-Chen YC Risch Harvey A HA Goodarzi Mark O MO Nuckols Teryl K TK Freedland Stephen J SJ Pandol Stephen J SJ Pisegna Joseph R JR

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20211102 1

<h4>Background</h4>Worsening glycemic control indicates elevated risk of pancreatic ductal adenocarcinoma (PDAC). We developed prediction models for PDAC among those with worsening glycemic control after diabetes diagnosis.<h4>Methods</h4>In 2000-2016 records within the Veterans Affairs Health System (VA), we identified three cohorts with progression of diabetes: (i) insulin initiation (<i>n</i> = 449,685), (ii) initiation of combination oral hypoglycemic medication (<i>n</i> = 414,460), and (ii ...[more]

PMID: 34728468

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Project description:PurposeImpaired glucose metabolism is present in most patients with pancreatic ductal adenocarcinoma (PDAC). Whereas previous studies have focused on pre-treatment glycemic indices and prognosis in those with concomitant diabetes, the effects of glycemic control during chemotherapy treatment on prognosis, in patients with and without diabetes, have not been well characterized. We examined the relationship between early glycemic control and overall survival (OS) in a cohort of patients with advanced PDAC treated in a community setting.Patients and methodsSeventy-three patients with advanced PDAC (38% with diabetes) receiving chemotherapy while participating in a biobanking clinical trial were included. Clinical characteristics and laboratory results during 1 year were obtained from the electronic medical record. Kaplan-Meier estimate, log-rank test and hazard ratios were computed to assess the effect of glycemic control on OS. The Cox proportional hazards regression model was applied to ascertain the significance of glycemic control with other survival variables.ResultsOne thousand four hundred eighteen random blood glucose (RBG) values were analyzed. In accord with previous findings, a 50% decline in the serum tumor marker CA 19-9 at any time was predictive of survival (P=0.0002). In univariate analysis, an elevated pre-treatment average RBG, 3-month average RBG (RBG-3) and the FOLFIRINOX regimen were associated with longer survival. Based on ROC analysis (AUC=0.82), an RBG-3 of 120 mg/dl was determined to be the optimal cutoff to predict 12-month survival. In multivariate analysis that included age, stage, BMI, performance status, presence of diabetes, and chemotherapy regimen, only RBG-3 maintained significance: an RBG-3 ≤120 mg/dl predicted for improved OS compared to >120 mg/dl (19 vs. 9 months; HR=0.37, P=0.002). In contrast, an early decline in CA 19-9 could not predict OS.ConclusionLower glucose levels during the first 3 months of treatment for advanced PDAC predict for improved OS in patients both with and without diabetes. These results suggest that RBG-3 may be a novel prognostic biomarker worthy of confirmation in a larger patient cohort and that studies exploring a possible cause and effect of this novel survival-linked relationship are warranted.

Project description:Background Early randomized controlled trials have demonstrated the benefits of tight glucose control. Subsequent NICE-SUGAR study found that tight glucose control increased mortality. The optimal glucose target in diabetic and nondiabetic patients remains unclear. This study aimed to evaluate the relationship between blood glucose levels and outcomes in critically ill patients with or without diabetes. Methods This was a retrospective analysis of the eICU database. Repeat ICU stays, ICU stays of less than 2 days, patients transferred from other ICUs, those with less than 2 blood glucose measurements, and those with missing data on hospital mortality were excluded. The primary outcome was hospital mortality. Generalised additive models were used to model relationship between glycemic control and mortality. Models were adjusted for age, APACHE IV scores, body mass index, admission diagnosis, mechanical ventilation, and use of vasopressor or inotropic agents. Results There were 52,107 patients in the analysis. Nondiabetes patients exhibited a J-shaped association between time-weighted average glucose and hospital mortality, while this association in diabetes patients was right-shifted and flattened. Using a TWA glucose of 100 mg/dL as the reference value, the adjusted odds ratio (OR) of TWA glucose of 140 mg/dL was 3.05 (95% confidence interval (CI) 3.03–3.08) in nondiabetes and 1.14 (95% CI 1.08–1.20) in diabetes patients. The adjusted OR of TWA glucose of 180 mg/dL were 4.20 (95% CI 4.07–4.33) and 1.49 (1.41–1.57) in patients with no diabetes and patients with diabetes, respectively. The adjusted ORs of TWA glucose of 80 mg/dL compared with 100 mg/dL were 1.74 (95% CI 1.57–1.92) in nondiabetes and 1.36 (95% CI 1.12–1.66) in patients with diabetes. The glucose ranges associated with a below-average risk of mortality were 80–120 mg/dL and 90–150 mg/dL for nondiabetes and diabetes patients, respectively. Hypoglycemia was associated with increased hospital mortality in both groups but to a lesser extent in diabetic patients. Glucose variability was positively associated with hospital mortality in nondiabetics. Conclusions Time-weighted average glucose, hypoglycemia, and glucose variability had different impacts on clinical outcomes in patients with and without diabetes. Compared with nondiabetic patients, diabetic patients showed a more blunted response to hypo- and hyperglycemia and glucose variability. Glycemic control strategies should be reconsidered to avoid both hypoglycemia and hyperglycemia. Supplementary Information The online version contains supplementary material available at 10.1186/s12871-022-01769-4.

Dataset Information

Prediction of Pancreatic Cancer in Diabetes Patients with Worsening Glycemic Control.

Background

Methods

Results

Conclusions

Impact

Publications

Prediction of Pancreatic Cancer in Diabetes Patients with Worsening Glycemic Control.

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