Amelioration of Cardiac Morphology and Function in Type 1 Diabetic Patients With Sustained Success of Pancreas Transplant Alone

Pancreas transplant alone (PTA) is coming of age for the treatment of selected type 1 diabetic (T1D) patients (1). By restoring endogenous insulin secretion, it eliminates acute diabetes complications and may improve late microvascular complications (1,2). However, the impact of PTA on the recipient’s heart is largely unknown. Here, we report that successful PTA is associated with long-term amelioration of cardiac morphology and function.

As of December 2013, 93 PTAs have been performed in our center, with 5-year patient and pancreas survival of 97 and 76%, respectively (2). Indications and contraindications for PTA, surgery, and immunosuppression were as previously reported (1,2). From this cohort, 30 consecutive successfully transplanted patients (males 50%; age 38 ± 8 years; BMI 24.0 ± 2.8 kg/m²; diabetes duration 25 ± 9 years; insulin dose 47 ± 13 units/day; anti-GAD and/or anti-IA2 positivity 36.6%; smokers 27%) with a complete post-PTA follow-up of 8 years were selected, provided their blood pressure values were similar before and after transplantation. Clinical investigations were performed by standard procedures, and Doppler echocardiographic examinations (Sonos 5500 Echograph, Agilent Technologies, Andover, MA) were accomplished by a single operator (L.R.). Results are given as mean ± SD and compared by the paired Student t test.

During follow-up, no major cardiovascular event occurred. Fasting plasma glucose and HbA_1c normalized, due to restored insulin secretion (Table 1). Total and LDL cholesterol decreased, with no change in the proportion of patients on statins (24% both before and after PTA) or statin dose. Systolic (SBP) and diastolic (DBP) blood pressure values were similar before and after PTA, with substantially unchanged antihypertensive therapy. Left ventricular ejection fraction, left ventricular mass, left ventricular mass index, left ventricular posterior wall thickness during diastole, and the E wave/A wave ratio improved significantly after PTA, with other parameters trending to do so (Table 1). In these patients, glomerular filtration rate (according to the MDRD formula) decreased from 80.0 ± 18.9 to 63.6 ± 22.4 mL/min (at a rate of 1.8 ± 2.7 mL/min/year).

Diabetes is associated with higher risk of cardiovascular disease, with diastolic cardiomyopathy representing a specific feature, and left ventricular diastolic dysfunction is considered a potential early sign of diastolic alterations. In this study, restored normoglycemia by successful PTA is associated with improvement of echocardiographic parameters, including diastolic indexes. These long-term results corroborate earlier observations (6 months after transplantation) in 13 PTA subjects with improved blood pressure after transplantation (this represents a potential confounder [3]) and extend data reported at 5 years after PTA (2). In the present study, SBP, DBP, and antihypertensive therapy were similar before and after PTA, suggesting that changes in echocardiographic parameters were not due to these variables. Improvements occurred despite a decline of glomerular filtration rate, which was not higher than that reported in nontransplanted T1D patients (4). In addition, it should be kept in mind that also tacrolimus, an immunosuppressant used by all the patients, may affect cardiac parameters. Of note, parameters of cardiac diastolic function have been shown to deteriorate in T1D, correlating with diabetes duration (5). Patients with pancreas and kidney transplantation experience beneficial effects on the cardiovascular system, including reduced cardiovascular mortality (1,2). Here, we show that successful PTA leads to amelioration of cardiac morphology and function, including diastolic indexes. Further work is needed to assess if this can impact cardiovascular outcomes in longer follow-up.