Fasting Pancreatic Polypeptide: A Novel Marker of Cardiovascular Risk and Coronary Artery Disease in Men with Type 2 Diabetes Mellitus

Presentation Number: MON 587
Date of Presentation: April 3rd, 2017

Amir H Sam*1, Adam Buckley2, Karim Meeran1, Paul Bech3, Maha Taysir Barakat2, Stephen R Bloom4, Nader Lessan2 and Kevin G. Murphy3
1Imperial College NHS Healthcare Trust, London, United Kingdom, 2Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates, 3Imperial College London, London, United Kingdom, 4Imperial College London, United Kingdom

Abstract

Coronary artery disease (CAD) is two to three times more prevalent in people with type 2 diabetes (T2DM), but it is often clinically silent and missed as a diagnosis in this group. Stratification of CAD risk in this population therefore provides valuable, clinically relevant information and guides primary preventive strategies. Pancreatic polypeptide (PP) is a peptide hormone released by the pancreas and regulated by vagal efferents. Fasting PP (fPP) is associated with visceral adiposity and is significantly increased in people with T2DM but not in people with impaired fasting glucose or impaired glucose tolerance, which are not as strongly associated with CAD. We have shown that, correcting for known risk factors, age, and renal function, fPP is increased in people with diabetic retinopathy or microalbuminuria, but the potential role for PP as a marker for macrovascular disease has not previously been investigated. We hypothesized that fPP would be elevated in people with established CAD. We examined data from 1,332 fasted adult participants with normal glucose tolerance (n=231), prediabetes (n=175) or T2DM (n=926) recruited at a diabetes and general endocrine clinic in Abu Dhabi. Fasting plasma PP was measured using an in-house radioimmunoassay. We estimated ten-year Framingham risk for each participant using the calculator incorporating lipid profile. CAD was defined as specialist diagnosis in combination with a record of either regional wall motion abnormality or angiographically proven disease. Fifty-one male (8.7%) and twenty-eight female (3.8%) participants met this endpoint. Correcting for estimated glomerular filtration rate (eGFR), PP was significantly correlated with Framingham ten-year risk (R2=0.39, p < 0.0001). In male participants with T2DM, log-transformed PP (log10PP) was an independent predictor of the CAD endpoint in logistic regression (OR 5.954 (1.554-22.813, p < 0.01) when corrected for age, BMI, diabetes duration, HbA1c, insulin use, number of oral hypoglycemic agents, systolic blood pressure (sBP), number of antihypertensive agents (AHAs), HDL:TC ratio, statin use, current smoking status and eGFR; as expected, age, sBP and number of AHAs were also independent predictors. Log10PP remained an independent predictor in logistic regression with the same covariates in all male participants (OR 4.503 (1.350-15.021), p < 0.05). PP alone had modest predictive value for the CAD endpoint (PPV 0.17, NPV 0.92, AUC ROC 0.657), superior to waist circumference (PPV 0.12, NPV 0.89, AUC ROC 0.486). Fasting PP may provide a more accurate marker of the contribution of central obesity to vascular risk than external measures of body composition.

 

Nothing to Disclose: AHS, AB, KM, PB, MTB, SRB, NL, KGM