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Follow-up of secondary diabetic complications after pancreas transplantation

Boggi, Ugoa; Rosati, Carlo Mariaa; Marchetti, Pierob

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Current Opinion in Organ Transplantation: February 2013 - Volume 18 - Issue 1 - p 102-110
doi: 10.1097/MOT.0b013e32835c28c5
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Pancreas transplantation can replenish the lost insulin secretion in patients with complicated type 1 diabetes mellitus and in selected patients with type 2 diabetes mellitus [1▪▪,2,3▪,4▪]. However, notwithstanding the improvements of the past decades [5▪▪,6▪,7▪▪,8▪,9], pancreas transplantation remains a major surgical undertaking, associated with sizeable early morbidity and mortality, and with mandatory life-long immunosuppression. The beneficial effects of pancreas transplantation must therefore be carefully balanced against its risks.

Successful pancreas transplantation induces full insulin independence, thus avoiding both acute complications of diabetes mellitus and side-effects of life-long insulin therapy [10]. In addition, evidence is growing to show that combined pancreas and kidney transplantation in type 1 diabetes mellitus is a life-saving procedure [1▪▪,5▪▪,7▪▪,11,12▪▪,13,14]. At the same time, the debate continues if pancreas transplantation can improve the course of chronic diabetic complications [15,16].

Tight glycemic control, as provided by intensive insulin regimens, may in part prevent progression of chronic diabetic complications [17], and beneficial effects of even a limited period of intensive glycemic control persist in the long term (metabolic legacy) [18–20]. Moreover, the benefit of measurable levels of C-peptide for the vessels has been demonstrated previously [21].

As pancreas transplantation candidates usually present with a long history of diabetes, most of them have already developed far advanced chronic diabetic complications. Avoidance of acute diabetic complications is a prerequisite for successful pancreas transplantation. On the contrary, the tempo of progression of chronic complications is much more delayed, requiring a longer follow-up to assess a potential effect of pancreas transplantation on them.

Box 1
Box 1:
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In this article we briefly review current evidence on the impact of pancreas transplantation on overall patient survival to then scrutinize the most recent literature regarding the impact of pancreas transplantation on the course of both microvascular and macrovascular complications of diabetes mellitus.


Pancreas transplantation can be performed in diabetic patients with or without end-stage renal disease (ESRD). Uremic patients often receive a simultaneous pancreas kidney transplantation (SPK), posturemic patients may receive a pancreas after kidney transplantation (PAK), whereas patients with preserved native renal function may receive a pancreas transplantation alone (PTA). In the latter two categories, pancreas transplantation is referred to as ‘solitary’, because of the lack of a kidney from the same donor.

According to the International Pancreas Transplant Registry, the current unadjusted patient survival rates at 5 years after pancreas transplantation are 87% for SPK, 83% for PAK, and 89% for PTA [5▪▪]. Patient and pancreas graft survival curves achieved at the University of Pisa are reported in Fig. 1[1▪▪].

Patient (a) and pancreas graft (b) survival up to 60 months after pancreas transplantation divided by recipient category (simultaneous pancreas and kidney transplantation, SPK; pancreas after kidney transplantation, PAK; pancreas transplantation alone, PTA) according to our single-center experience (University of Pisa). Reproduced from [1▪▪].

For the diabetic patient with ESRD there are many therapeutic options [22▪▪], including dialysis, living donor or deceased donor kidney transplantation alone (KTA), with or without a subsequent PAK, and SPK, which in rare occasions has also been performed utilizing a kidney and a segmental pancreas graft from the same living donor [23▪,24▪], or by concurrently transplanting a deceased donor pancreas and a living donor kidney [25,26]. Moreover, each transplant can be performed before or after starting dialysis [27▪].

Notwithstanding its early postoperative risk (2–5% absolute mortality rate in the first year) and some conflicting reports [28,29▪], SPK offers significant long-term survival advantage over both deceased donor and living donor KTA [11,12▪▪,13,14,22▪▪,27▪].

For the patient lucky enough to have a potential living donor kidney, the decision to undergo KTA first with subsequent PAK, or to wait for an upfront SPK is not straightforward, being influenced by the needs of the individual patient and local waiting times for pancreas transplantation. In general, living donor KTA should be considered a valid alternative to SPK for all patients already on dialysis [22▪▪].

The importance of pancreas graft function after pancreas transplantation is highlighted by the fact that the relative risk for patient mortality increases by 3–4-fold after pancreas graft failure in SPK and PAK recipient and by 11-fold in PTA recipients [5▪▪]. Since the survival advantage of an SPK over a living donor KTA is dependent upon the function of the pancreas graft [30–32,33▪], a pancreas donor risk index has been developed to maximize the acceptance of all suitable donors for pancreas transplantation [34].

Whereas an SPK usually provides more durable pancreas graft function than a PAK, supporting SPK as the ‘ideal’ option, a successful PAK provides a long-term survival advantage, too [30,35–37,38▪,39].

Regarding PTA, whereas a first analysis performed by Venstrom et al.[40] apparently showed an increased relative risk of death for pancreas transplantation recipients as compared to patients remaining in the waiting list, Gruessner et al.[41,42] reanalyzed the same data, correcting for multiple listings and recipient category misclassifications, and did not confirm the higher mortality risk for PTA recipients. However, since there is no clear-cut evidence of a survival advantage for PTA, the rationale of this operation [2] should stand in its ability to prevent the acute complications of diabetes mellitus, to modify the evolution of the chronic complications and to improve quality of life.


Pancreas transplantation, in its several forms, has beneficial effects on lipid profile and blood pressure [43–45]. We recently reported our experience with 71 PTA [46▪▪,47▪▪]. After a 5-year follow-up period there was a significant reduction in serum total and low-density lipoprotein-cholesterol levels with no change in high-density lipoprotein-cholesterol and triglyceride levels, despite similar use of statins, and improved SBP and DBP control, without relevant differences in the use of antihypertensive medications.

Of interest, SPK is able to correct hemostatic abnormalities that are present in uremic type 1 diabetic patients more effectively than KTA [48]. Pancreas transplantation is also able to reverse pathologic inflammatory pathways that are evident in skin biopsies of T1D patients using techniques such as proteomics, clinical biochemistry, electron microscopy, and immunohistochemistry [49].


Retinopathy, nephropathy, and neuropathy are the classical microvascular complications of DM.


Despite early conflicting evidence [50–57], partially compounded by inconsistent classification systems used to grade the disease, it is now clear that pancreas transplantation slows the progression, stabilizes, and even reverses diabetic retinopathy and macular edema (Fig. 2) [58,59]. We compared the evolution of both nonproliferative and proliferative or laser-treated retinopathy in a group of 48 patients who underwent SPK with a control group of 43 nontransplanted type 1 diabetic patients. Diabetic retinopathy and its improvement/deterioration were assessed according to the criteria proposed by the EURODIAB Study [60]. At a median follow-up of 17 months (range 6–60 months), the number of improved/stabilized patients was significantly higher in the transplanted group [58].

Beneficial effects of pancreas transplantation on diabetic retinopathy. Photographs of the retina of a patient showing laser-treated retinopathy. (a) Before pancreas transplantation alone (PTA); (b) 13 months after PTA. The most apparent improvement was reduction/disappearance of exudates. Reproduced from [59].

Similarly, we prospectively studied the course of diabetic retinopathy in 33 PTA recipients (follow-up 30 ± 11 months) and in 35 control nontransplanted type 1 diabetic patients (follow-up 28 ± 10 months) and found that the percentage of patients with improved or stabilized diabetic retinopathy was significantly higher in the PTA group [59]. Likewise, our most recent data (71 patients) confirm the positive impact of PTA on ocular complications of diabetes mellitus after 4 years of follow-up [46▪▪]. However, no beneficial effects have instead been reported on other ocular complications, such as cataract and glaucoma [59,61].


Type 1 diabetes mellitus patients are at extremely high risk of developing renal complications. Progression to ESRD in this patient population has grim prognostic implications [62,63] and proves to be resistant to most nephroprotective therapeutic measures [64▪]. Pancreas transplantation prevents the recurrence of diabetic nephropathy in renal allografts and may slow the progression, stabilize, and even reverse the course of the disease in native kidneys. These facts are proven by functional and histologic evidence. In SPK recipients the presence of a functioning pancreas improves renal graft survival as compared to KTA, and this advantage is dependent on pancreas graft function: pancreas graft failure during the first 90 days [31,33▪] or the first year [32] after the procedure is a strong risk factor for the subsequent loss of the kidney graft, too.

Despite lower pancreas graft survival, as compared to SPK, PAK improves kidney graft survival in the long term [36,37,38▪]. The beneficial impact of PAK on kidney graft function is highly dependent on the time interval between the two transplants, which should be shorter than 1 year [65,66▪].

The effects of PTA on renal function are still a matter of debate. Currently available immunosuppressive drugs are nephrotoxic, and this places pancreas transplantation recipients, like other solid organ recipients [67], at risk for post-transplant nephropathy [68▪,69]. The renal function of diabetic patients without overt ESRD who are referred for pancreas transplantation must be adequately assessed in order to counsel them about the best transplant alternative (solitary pancreas transplantation vs. preemptive SPK) [70,71]. The ideal management of patients with borderline renal function is still controversial [72▪▪]. Gruessner et al.[73] showed that a serum creatinine level above 1.5 mg/dL and recipient age below 30 years are significantly associated with development of overt renal failure after PTA. However, Chatzizacharias et al.[74▪] reported no significant deterioration of renal function at 1 year after PTA in patients with glomerular filtration rate (GFR) of about 50 ml/min.

We showed no significant change in creatinine concentration and clearance and an improvement in proteinuria at 1 year after PTA [75], and recently reported our updated findings on 71 PTA recipients 5 years after transplantation [46▪▪,47▪▪]. In this series proteinuria improved significantly, whereas only one patient developed ESRD. In the 51 patients with sustained pancreas graft function, kidney function (serum creatinine and glomerular filtration rate) decreased over time with a slower decline in recipients with pretransplant GFR less than 90 ml/min in comparison to those with pretransplant GFR greater than 90 ml/min (Fig. 3), possibly as a result of correction of hyperfiltration following normalization of glucose metabolism. This finding is in contrast to a previous study by Genzini et al.[76], who found an accelerated decline in renal function after PTA in the patient population with lower pretransplant GFR.

Estimated glomerular filtration rate (GFR) before and 4 years after pancreas transplantation alone (PTA) according to pretransplantation (pre-Tx) values in our recently reported single-center experience. * P < 0.01. Reproduced from [46▪▪].

The evolution of diabetic nephropathy has been well characterized both functionally and histologically [77–79]. Fioretto et al.[80,81] performed protocol biopsies in patients who had received a successful PTA and found that, whereas 5 years after transplant the histologic lesions of diabetic nephropathy were unaffected [80], at 10 years reversal of diabetic glomerular and tubular lesions was evident [81].

The histologic reversibility of diabetic nephropathy was previously shown in the case of transplantation of human cadaveric kidneys into nondiabetic recipients [82,83] and is supported by the current favorable outcome of deceased diabetic donor kidneys [84▪▪]. Accordingly, using 31P-magnetic resonance spectroscopy to assess high-energy phosphate metabolism in the kidney graft of type 1 diabetes mellitus patients who had undergone KTA or SPK, Fiorina et al.[85] found that a functioning pancreas graft has beneficial effects on metabolism of the kidney graft.


Diabetic neuropathy develops in the majority of patients with a long history of diabetes mellitus, and it exacts a heavy toll in terms of morbidity and mortality [86,87▪]. When referred for pancreas transplantation, diabetic patients usually have far-advanced neuropathy. However, pancreas transplantation has beneficial effects on diabetic neuropathy (sensory, motor, and autonomic), as assessed by clinical scores of symptoms, physical examination (including qualitative sensory testing), nerve conduction studies and other electrophysiological measurements, and autonomic function tests [88–92]. These benefits have been reported for all types of pancreas transplantation. Navarro et al.[91] compared the evolution of diabetic neuropathy in 115 patients with a functioning pancreas transplantation (31 SPK, 31 PAK, 43 PTA without and 10 PTA with subsequent kidney transplantation) and 92 control patients along 10 years of follow-up. Using clinical examination, nerve conduction studies, and autonomic function tests, the authors found significant improvements in the transplanted groups (similar across the different subgroups) [91]. Interestingly, Martinenghi et al.[92] monitored nerve conduction velocities in five patients who underwent SPK, reporting a significant improvement which was strictly dependent on pancreas graft function. In addition, we found a significant improvement in Michigan Neuropathy Screening Instrument scores [93], vibration perception thresholds, nerve conduction studies, and autonomic function tests in a series of PTA patients with long-term follow-up [46▪▪,47▪▪]. The beneficial effects of pancreas transplantation on cardiac autonomic neuropathy were also reported by Cashion et al.[94] using 24 h heart rate variability monitoring. However, spectral analysis of heart rate variation was performed by Boucek et al.[95], but without significant findings.

Nerve regeneration is defective in diabetic patients [86]. In a case report, Beggs et al.[96] performed sequential sural nerve biopsies after PTA and found histologic evidence of nerve regeneration. Quantification of nerve fiber density in skin biopsies [97–99] or in gastric mucosal biopsies obtained during endoscopy [100] is an interesting tool to assess diabetic neuropathy. However, Boucek et al.[101,102] did not find any significant improvement in intraepidermal nerve fiber density after pancreas transplantation. In contrast, Mehra et al. used corneal confocal microscopy, a noninvasive and well validated imaging technique [103,104], and were able to find significant small nerve fiber repair within 6 months after pancreas transplantation [105].


Cardiovascular events represent a primary cause of morbidity and mortality after pancreas transplantation [106], both in the immediate postoperative period [107] and in the long term [108].

It is essential to perform a thorough preoperative cardiac evaluation of pancreas transplantation candidates, and for that goal widely available and applied clinical and instrumental tests (like electrocardiogram, transthoracic echocardiography, and coronary angiography) [109,110], might be integrated or partially replaced by others, such as myocardial perfusion scintigraphy [111▪].

Despite previous conflicting reports [112–115], in (pre)uremic type I diabetic patients, SPK offers clear benefits (strictly dependent on a functioning pancreatic graft [116]) compared to medical management or even KTA, reflecting reduction in overall mortality and specifically in cardiovascular mortality, reduced incidence of myocardial infarctions [117–119], improvement of left-ventricular function [118–120], improved cardiac metabolism as assessed by 31P magnetic resonance spectroscopy [121], reduced incidence of cerebrovascular disease [119], and improvement of carotid atherosclerosis (as evaluated by intima media thickness) [43,122,123] and of peripheral arterial disease (PAD) [119].

In order to assess the impact of pancreas transplantation on macrovascular complications of diabetes mellitus, a sufficiently long follow-up is necessary. Whereas Biesenbach et al.[112] (mean follow-up 70 months) and Knight et al.[113] (median follow-up 45 months) reported no differences between SPK and KTA in their impact on PAD, and Morrissey et al.[114] (mean follow-up 4 years) reported even worse vascular outcomes for SPK vs. KTA patients, in a different study, Biesenbach et al.[119] found no significant differences at 5-year follow-up, but a significantly better outcome for SPK vs. KTA at 10-year follow-up.

Evidence is growing about the positive impact on macrovascular complications of PTA, too. As we recently reported [46▪▪,47▪▪], in our center, 71 patients underwent PTA with a 5-year follow-up, showing slight but significant improvement in both diastolic and systolic cardiac function.


Pancreas transplantation, if timely performed, is able to slow the progression, stabilize, and even reverse chronic complications of diabetes mellitus (Table 1). In this regard, advantages of SPK are widely accepted. Whereas the role of solitary pancreas transplantation is more debated, growing data are becoming available in its favor.

Table 1
Table 1:
Effects of a successful pancreas transplantation (insulin independence and optimal glycemic control) on cardiovascular risk factors and chronic complications of diabetes

In order to adequately assess the impact of pancreas transplantation on diabetes mellitus complications, however, it is essential to use validated and accurate diagnostic tools and grading systems. Histologic proof of the potential reversibility of microvascular complications of diabetes mellitus after pancreas transplantation has shed new light on the pathophysiology of this disease and of organs affected. Interesting techniques are emerging as powerful tools for unprecedented monitoring of the evolution of diabetic complications. Noninvasive functional imaging techniques have great potential. Corneal confocal microscopy, for instance, has shown the reversibility of diabetic neuropathy after pancreas transplantation and has been proposed as a sensitive tool for the early diagnosis of this complication in the diabetic population at large [103–105].

Together with improving the surgical and immunological aspects of pancreas transplantation, a thorough understanding of its potential benefits allows to adequately counsel each individual diabetic patient.



Conflicts of interest

Disclosure of funding: none.


Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest

Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 125–126).


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This study provides a comprehensive review of pancreas transplantation practice and outcomes.

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After adjustment for multiple risk factors, no different outcomes (patient and organ survival) were found between type 1 and type 2 diabetes mellitus recipients of SPK.

4▪. Orlando G, Stratta RJ, Light J. Pancreas transplantation for type 2 diabetes mellitus. Curr Opin Organ Transplant 2011; 16:110–115.

Up to 7% of SPK recipients are classified as having type 2 diabetes mellitus and their outcomes are comparable to type 1 diabetes mellitus recipients.

5▪▪. Gruessner AC. 2011 update on pancreas transplantation: comprehensive trend analysis of 25,000 cases followed up over the course of twenty-four years at the International Pancreas Transplant Registry (IPTR). Rev Diabet Stud 2011; 8:6–16.

The most recent analysis of the data from the International Pancreas Transplant Registry: a must-read text.

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An excellent review on the topic.

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Long-term graft survival continues to be less than optimal.

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A review on the topic from the group with the largest experience in the world.

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Early (<90 days) pancreas graft failure in SPK transplant recipients is associated with an increased risk for subsequent kidney failure and death.

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71. Lane JT, Ratanasuwan T, Mack-Shipman R, et al. Cyclosporine challenge test revisited: does it predict outcome after solitary pancreas transplantation? Clin Transplant 2001; 15:28–31.
72▪▪. Smail N, Paraskevas S, Tan X, et al. Renal function in recipients of pancreas transplant alone. Curr Opin Organ Transplant 2012; 17:73–79.

The ideal management of candidates for PTA with eGFR less than 60 ml/min/1.73 m2 remains controversial.

73. Gruessner RW, Sutherland DE, Kandaswamy R, et al. Over 500 solitary pancreas transplants in nonuremic patients with brittle diabetes mellitus. Transplantation 2008; 85:42–47.
74▪. Chatzizacharias NA, Vaidya A, Sinha S, et al. Renal function in type 1 diabetics one year after successful pancreas transplantation. Clin Transplant 2011; 25:E509–515.

Renal function did not deteriorate significantly one year after pancreas transplant (PTA or PAK), even in patients with substantial pre-existing renal dysfunction.

75. Coppelli A, Giannarelli R, Vistoli F, et al. The beneficial effects of pancreas transplant alone on diabetic nephropathy. Diabetes Care 2005; 28:1366–1370.
76. Genzini T, Marchini GS, Chang AJ, et al. Influence of pancreas transplantation alone on native renal function. Transplant Proc 2006; 38:1939–1940.
77. Fioretto P, Caramori ML, Mauer M. The kidney in diabetes: dynamic pathways of injury and repair. The Camillo Golgi Lecture 2007. Diabetologia 2008; 51:1347–1355.
78. Steinke JM. The natural progression of kidney injury in young type 1 diabetic patients. Curr Diab Rep 2009; 9:473–479.
79. Fornoni A. Proteinuria, the podocyte, and insulin resistance. N Engl J Med 2010; 363:2068–2069.
80. Fioretto P, Mauer SM, Bilious RW, et al. Effects of pancreas transplantation on glomerular structure in insulin-dependent diabetic patients with their own kidneys. Lancet 1993; 342:1193–1196.
81. Fioretto P, Steffes MW, Sutherland DE, et al. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 1998; 339:69–75.
82. Abouna GM, Al-Adnani MS, Kremer GD, et al. Reversal of diabetic nephropathy in human cadaveric kidneys after transplantation into nondiabetic recipients. Lancet 1983; 2:1274–1276.
83. Abouna GM, Adnani MS, Kumar MS, Samhan SA. Fate of transplanted kidneys with diabetic nephropathy. Lancet 1986; 1:622–623.
84▪▪. Mohan S, Tanriover B, Ali N, et al. Availability, utilization and outcomes of deceased diabetic donor kidneys: analysis based on the UNOS registry. Am J Transplant 2012; 12:2098–2105.

Both overall and death-censored survival of organs from diabetic standard criteria donors was significantly better than that of organs obtained from nondiabetic extended criteria donors, while inferior to that from nondiabetic standard criteria donors. More recently, many diabetic donor kidneys have been given to diabetic recipients with early graft survival being similar to that among nondiabetic recipients.

85. Fiorina P, Perseghin G, De Cobelli F, et al. Altered kidney graft high-energy phosphate metabolism in kidney-transplanted end-stage renal disease type 1 diabetic patients: a cross-sectional analysis of the effect of kidney alone and kidney-pancreas transplantation. Diabetes Care 2007; 30:597–603.
86. Boucek P. Advanced diabetic neuropathy: a point of no return? Rev Diabet Stud 2006; 3:143–150.
87▪. Shakher J, Stevens MJ. Update on the management of diabetic polyneuropathies. Diabetes Metab Syndr Obes 2011; 4:289–305.

A useful review on the topic.

88. Kennedy WR, Navarro X, Goetz FC, et al. Effects of pancreatic transplantation on diabetic neuropathy. N Engl J Med 1990; 322:1031–1037.
89. Hathaway DK, Abell T, Cardoso S, et al. Improvement in autonomic and gastric function following pancreas-kidney versus kidney-alone transplantation and the correlation with quality of life. Transplantation 1994; 57:816–822.
90. Allen RD, Al Harbi IS, Morris JG, et al. Diabetic neuropathy after pancreas transplantation: determinants of recovery. Transplantation 1997; 63:830–838.
91. Navarro X, Sutherland DE, Kennedy WR. Long-term effects of pancreatic transplantation on diabetic neuropathy. Ann Neurol 1997; 42:727–736.
92. Martinenghi S, Comi G, Galardi G, et al. Amelioration of nerve conduction velocity following simultaneous kidney/pancreas transplantation is due to the glycaemic control provided by the pancreas. Diabetologia 1997; 40:1110–1112.
93. Feldman EL, Stevens MJ, Thomas PK, et al. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care 1994; 17:1281–1289.
94. Cashion AK, Hathaway DK, Milstead EJ, et al. Changes in patterns of 24-hr heart rate variability after kidney and kidney-pancreas transplant. Transplantation 1999; 68:1846–1850.
95. Boucek P, Saudek F, Adamec M, et al. Spectral analysis of heart rate variation following simultaneous pancreas and kidney transplantation. Transplant Proc 2003; 35:1494–1498.
96. Beggs JL, Johnson PC, Olafsen AG, et al. Signs of nerve regeneration and repair following pancreas transplantation in an insulin-dependent diabetic with neuropathy. Clin Transplant 1990; 4:133–141.
97. Kennedy WR, Wendelschafer-Crabb G, Johnson T. Quantitation of epidermal nerves in diabetic neuropathy. Neurology 1996; 47:1042–1048.
98. Beiswenger KK, Calcutt NA, Mizisin AP. Epidermal nerve fiber quantification in the assessment of diabetic neuropathy. Acta Histochem 2008; 110:351–362.
99. Nolano M, Provitera V, Caporaso G, et al. Quantification of pilomotor nerves: a new tool to evaluate autonomic involvement in diabetes. Neurology 2010; 75:1089–1097.
100. Selim MM, Wendelschafer-Crabb G, Redmon JB, et al. Gastric mucosal nerve density: a biomarker for diabetic autonomic neuropathy? Neurology 2010; 75:973–981.
101. Boucek P, Havrdova T, Voska L, et al. Severe depletion of intraepidermal nerve fibers in skin biopsies of pancreas transplant recipients. Transplant Proc 2005; 37:3574–3575.
102. Boucek P, Havrdova T, Voska L, et al. Epidermal innervation in type 1 diabetic patients: a 2.5-year prospective study after simultaneous pancreas/kidney transplantation. Diabetes Care 2008; 31:1611–1612.
103. Malik RA, Kallinikos P, Abbott CA, et al. Corneal confocal microscopy: a noninvasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia 2003; 46:683–688.
104. Tavakoli M, Hossain P, Malik RA. Clinical applications of corneal confocal microscopy. Clin Ophthalmol 2008; 2:435–445.
105. Mehra S, Tavakoli M, Kallinikos PA, et al. Corneal confocal microscopy detects early nerve regeneration after pancreas transplantation in patients with type 1 diabetes. Diabetes Care 2007; 30:2608–2612.
106. Sollinger HW, Odorico JS, Becker YT, et al. One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up. Ann Surg 2009; 250:618–630.
107. Medina-Polo J, Domínguez-Esteban M, Morales JM, et al. Cardiovascular events after simultaneous pancreas-kidney transplantation. Transplant Proc 2010; 42:2981–2983.
108. Näf S, José Ricart M, Recasens M, et al. Macrovascular events after kidney-pancreas transplantation in type 1 diabetic patients. Transplant Proc 2003; 35:2019–2020.
109. Fossati N, Meacci L, Amorese G, et al. Cardiac evaluation for simultaneous pancreas-kidney transplantation and incidence of cardiac perioperative complications: preliminary study. Transplant Proc 2004; 36:582–585.
110. Rondinini L, Mariotti R, Cortese B, et al. Echocardiographic evaluation in type 1 diabetic patients on waiting list for isolated pancreas or kidney-pancreas transplantation. Transplant Proc 2004; 36:457–459.
111▪. Ruparelia N, Bhindi R, Sabharwal N, et al. Myocardial perfusion is a useful screening test for the evaluation of cardiovascular risk in patients undergoing simultaneous pancreas kidney transplantation. Transplant Proc 2011; 43:1797–1800.

Myocardial perfusion scintigraphy may be a useful tool during pretransplant cardiac evaluation.

112. Biesenbach G, Margreiter R, Königsrainer A, et al. Comparison of progression of macrovascular diseases after kidney or pancreas and kidney transplantation in diabetic patients with end-stage renal disease. Diabetologia 2000; 43:231–234.
113. Knight RJ, Zela S, Schoenberg L, et al. The effect of pancreas transplantation on peripheral vascular disease complications. Transplant Proc 2004; 36:1069–1071.
114. Morrissey P, Shaffer D, Monaco A, et al. Peripheral vascular disease after kidney-pancreas transplantation in diabetic patients with end-stage renal disease. Arch Surg 1997; 132:358–361.
115. Nankivell BJ, Lau SG, Chapman JR, et al. Progression of macrovascular disease after transplantation. Transplantation 2000; 69:574–581.
116. Jukema J, Smets Y, van der Pijl J, et al. Impact of simultaneous pancreas and kidney transplantation on progression of coronary atherosclerosis in patients with end stage renal failure due to type 1 diabetes. Diabetes Care 2002; 25:906–911.
117. La Rocca E, Fiorina P, Astorri E, et al. Patient survival and cardiovascular events after kidney-pancreas transplantation: comparison with kidney transplantation alone in uremic IDDM patients. Cell Transplant 2000; 9:929–932.
118. La Rocca E, Fiorina P, Di Carlo V, et al. Cardiovascular outcomes after kidney-pancreas and kidney alone transplantation. Kidney Int 2001; 60:1964–1971.
119. Biesenbach G, Konigsrainer A, Gross C, Margreiter R. Progression of macrovascular diseases is reduced in type 1 diabetic patients after more than 5 years successful combined pancreas–kidney transplantation in comparison to kidney transplantation alone. Transpl Int 2005; 18:1054–1060.
120. Fiorina P, La Rocca E, Astorri E, et al. Reversal of left ventricular diastolic dysfunction after kidney-pancreas transplantation in type 1 diabetic uremic patients. Diabetes Care 2000; 23:1804–1810.
121. Perseghin G, Fiorina P, De Cobelli F, et al. Cross-sectional assessment of the effect of kidney and kidney–pancreas transplantation on resting left ventricular energy metabolism in type 1 diabetic-uremic patients: a phosphorous-31 magnetic resonance spectroscopy study. J Am Coll Cardiol 2005; 46:1085–1092.
122. Larsen JL, Ratanasuwan T, Burkman T, et al. Carotid intima media thickness is decreased after pancreas transplantation. Transplantation 2002; 73:936–940.
123. Larsen JL, Colling CW, Ratanasuwan T, et al. Pancreas transplantation improves vascular disease in patients with type 1 diabetes. Diabetes Care 2004; 27:1706–1711.

chronic complications of diabetes; diabetes mellitus; macrovascular complications; microvascular complications; pancreas transplantation

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