HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jukema, J. W. Articles by de Fijter, J. W. Search for Related Content PubMed PubMed Citation Articles by Jukema, J. W. Articles by de Fijter, J. W. Social Bookmarking                What's this?

Impact of Simultaneous Pancreas and Kidney Transplantation on Progression of Coronary Atherosclerosis in Patients With End-Stage Renal Failure due to Type 1 Diabetes

¹ Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
² Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
³ Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
⁴ Department of Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands
⁵ Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands

	ABSTRACT

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
OBJECTIVE—Mortality in type 1 diabetic patients with end-stage renal failure is high and dominated by coronary atherosclerotic events. With regard to prognosis, simultaneous transplantation of pancreas and kidney (SPK) may be superior to kidney transplantation alone (KTA) in type 1 diabetic patients, because normalization of blood glucose levels may reduce progression of coronary atherosclerosis and because it is well known that progression of coronary atherosclerosis is one of the major factors that determines clinical prognosis. However, no data are available on progression of coronary atherosclerosis after SPK.

RESEARCH DESIGN AND METHODS—We performed an observational angiographic study comparing progression of coronary atherosclerosis, analyzed with quantitative coronary angiography, in patients with (n = 26) and those without (n = 6) a functioning pancreas graft after SPK, to test the hypothesis that normalization of blood glucose levels by SPK may indeed reduce progression of coronary atherosclerosis in type 1 diabetic patients and thereby improve prognosis.

RESULTS—Mean follow-up was 3.9 years. Average glucose control was significantly worse for the patients without a pancreas graft than for patients with a functioning pancreas graft: 11.3 (SD 3.5) vs. 5.9 mmol/l (SD 1.1) (P = 0.03). Mean segment diameter loss (progression of diffuse coronary atherosclerosis) was 0.024 mm/year (SD 0.067) in patients with a functioning pancreas graft, compared with 0.044 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Minimum obstruction diameter loss (progression of focal coronary atherosclerosis) was 0.037 mm/year (SD 0.086) in patients with a functioning pancreas graft compared with 0.061 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Regression of atherosclerosis occurred in 38% of patients with a functioning pancreas graft compared with 0% of patients of whom the pancreas graft was lost (P = 0.035).

CONCLUSIONS—Our study provides, for the first time, evidence that in patients who have undergone SPK, progression of coronary atherosclerosis in patients with a functioning pancreas graft is reduced compared with patients with pancreas graft failure. Our observation is an important part of the explanation for the observed improved mortality rates reported in type 1 diabetic patients with end-stage renal failure after SPK compared with KTA. In light of these findings described above, SPK must to be carefully considered for all diabetic transplant candidates.

Abbreviations: CAG, coronary arteriography • KTA, kidney transplantation alone • MOD, minimum obstruction diameter • MSD, mean segment diameter • PTCA, percutaneous transluminal coronary angioplasty • QCA, quantitative coronary arteriography • SPK, simultaneous transplantation of pancreas and kidney

	INTRODUCTION

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
Diabetes is an increasing worldwide health problem that often leads to severe medical and psychosocial problems, including blindness, kidney failure, amputation, and death (1). Mortality in type 1 diabetic patients with end-stage renal failure is high and dominated by coronary artery disease events (2). Although the possibilities of training and treating particularly young motivated patients with type 1 diabetes are numerous and nowadays rather sophisticated, none are able to normalize the metabolism of people who have been diabetic for years or even decades (3,4).

Simultaneous transplantation of pancreas and kidney (SPK) may be superior to kidney transplantation alone (KTA) in type 1 diabetic patients (5,6), because normalization of blood glucose levels might reduce progression of coronary atherosclerosis and because it is well known that progression of coronary atherosclerosis is one of the major factors that determines clinical prognosis (7–9). However, no data are available on progression of coronary atherosclerosis after SPK.

Because a randomized study comparing SPK with KTA to assess progression of coronary atherosclerosis is not ethically and practically feasible, we performed a well-controlled prospective observational angiographic study, comparing progression of coronary atherosclerosis in patients with and without a functioning pancreas graft (defined as need to reinstitute insulin therapy) after SPK, to evaluate the hypothesis that normalization of blood glucose levels by SPK may indeed reduce progression of coronary atherosclerosis in type 1 diabetic patients and thereby improve prognosis.

	RESEARCH DESIGN AND METHODS

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
Referrals for SPK
As part of a prospective study, 50 consecutive type 1 diabetic patients with end-stage renal failure were evaluated according to protocol and underwent SPK at the Leiden University Medical Center, Leiden, the Netherlands. All patients had additional secondary diabetic complications, including retinopathy and neuropathy. Preoperative workup, (surgical) procedure, transplant characteristics, as well as antibiotic and immunosuppression are described in detail elsewhere (10). The protocol was approved by the Institutional Review Board of the university. Preoperative workup also routinely included coronary arteriography (CAG) according to quantitative coronary arteriography (QCA) standards; therefore, no referral bias on the base of coronary angiography for a clinical reason is present. Patients underwent standardized follow-up CAG at least 2 years after transplantation to evaluate progression of coronary atherosclerosis. Also, clinical events (cardiac), death, myocardial infarction, revascularization procedures (percutaneous transluminal coronary angioplasty [PTCA] and coronary artery bypass grafting), and cerebrovascular events (cerebrovascular accident and transient ischemic attack) were monitored during follow-up. This report focuses on progression of coronary atherosclerosis as assessed by QCA.

QCA
For CAG and QCA analyses, the protocol of the Regression Growth Evaluation Statin Study (REGRESS) was followed (11). In brief, quality assurance of catheterization laboratory and cine films was strictly maintained (12). Only catheters approved for QCA were used (13). The distal tip of the catheter was cut off and sent to the QCA Core Laboratory (Heart Core, Leiden, the Netherlands) for measurement and was used as scaling device in the QCA analysis. Panning of the image had to be avoided as much as possible. The protocol required administration of coronary vasodilators (5–10 min before CAG, 5–10 mg isosorbide dinitrate was administered sublingually). The exact filming sequence of the initial coronary cinearteriography and the precise rotational and angulational views, as well as table height, were noted. Analysis of the coronary arteriograms was performed by QCA using the QCA-CMS system (MEDIS Medical Imaging Systems, Leiden, the Netherlands). For calibration, the boundaries of a nontapering part of the catheter were determined automatically over a length of 2 cm. To determine the contours of the vessel, the user only had to indicate the beginning and end of the coronary segment to be analyzed, after which a pathline was computed connecting these two points. The contours of the vessel were then computed in multiple iterations by the minimal cost contour detection technique.

For QCA, the coronary tree was divided into 13 segments, according to the American Heart Association classification, excluding the posterolateral branches. Obstructions within the 13 segments were coded and analyzed separately if the diameter narrowing was 20% at either baseline or follow-up. As a result, obstruction data were always available in paired format (baseline and follow-up), with at least one of the two severities 20% diameter stenosis. Baseline and follow-up coronary arteriograms of each patient were viewed simultaneously on a dual Tagarno projector (Tagarno A/S) by an experienced cardiologist blinded to pancreas graft function. The complete procedure is described in detail elsewhere (11) and has been extensively validated (12–16).

Angiographic end points
The angiographic end point was a comparison between the patients with a functioning pancreas graft and the patients without a functioning pancreas graft after initial successful SPK. Because the interval between the repeat angiographies was not fixed (range 2–5.5 years; requirement: at least 2 years) and progression is time dependent, we calculated annual rates of progression per patient. This annual-rate approach has been used and validated for other trials as well (17). The angiographic end points were defined as follows: 1) change in average mean segment diameter (MSD) on a by patient basis per year as parameter for diffuse changes/progression of coronary atherosclerosis; and 2) change in average minimum obstruction diameter (MOD) on a by patient basis per year as parameter for focal changes/progression of coronary atherosclerosis (Fig. 1). These definitions have been described earlier in detail and have been evaluated and validated extensively (11,14,17).

View larger version (19K): [in this window] [in a new window]   Figure 1— Stylized diagram of vessel indicating MSD and MOD. MSD = 1N/N.

	RESULTS

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
Follow-up CAG and clinical events
A total of 50 consecutive patients were included and prospectively followed (33 men and 17 women, mean age 38 years, mean duration of type 1 diabetes 24 years). Mean follow-up was 3.9 years. All patients had a baseline CAG; two patients were lost to follow-up. Therefore, in 48 patients (32 men and 16 women), an evaluable baseline CAG was available.

According to the protocol, i.e., before SPK and at least 2 years after SPK, 31 patients underwent follow-up CAG, on average of 3.9 years post-transplantation. No follow-up CAG was available in 17 patients: 7 due to death (4 cardiac) and 10 due to patient refusal. One additional patient lost pancreas function between the follow-up angiogram and a third angiogram, and angiographic values of this second time frame were also analyzed.

Of the 10 patients who refused to undergo follow-up CAG, seven had a functioning pancreas graft and three patients had no functioning pancreas graft.

Of the seven patients who died before follow-up CAG could be performed, five patients already had lost their pancreas graft; three of these patients died due to myocardial infarction, and the other two patients died due to infection. The two patients who died before follow-up CAG was performed and who had a functioning pancreas graft died due to myocardial infarction and infection, respectively.

During follow-up, only two nonfatal cardiovascular events occurred: one PTCA and one myocardial infarction, both in patients with a functioning pancreas graft.

Baseline characteristics of patients with and without follow-up CAG, including sex, age, BMI, duration of diabetes, months of dialysis, (immunosuppressant) medication, HbA_1c, albumin level, lipid level, blood pressure, smoking, number of rejection episodes, history of myocardial infarction, and amount of left ventricular dysfunction, did not differ, with the exception of sex; there were relatively more women without follow-up CAG.

The characteristics of patients in whom the pancreas graft was lost before follow-up CAG and patients who had a functioning pancreas at the time of follow-up CAG are summarized in Table 1. We found no significant differences. Therefore, patients without follow-up CAG or with loss of pancreas graft do not seem to be a selected group of the entire cohort, because such a selection is not reflected by the recorded baseline characteristics.

HbA_1c measurements yielded similar results (not available for all patients during follow-up).

Progression of coronary atherosclerosis related to pancreas graft survival
Within the group of 31 patients who underwent follow-up CAG, the pancreas graft was lost in five patients before follow-up CAG. As stated, in one additional patient, the pancreas was lost between the second and third angiogram. Consequently, we were able to compare 26 cases without pancreas graft loss with 6 cases with loss of the pancreas graft. In the analysis, we ignored the possible association. Five of the six cases were an early loss of graft function due to graft-thrombosis/early rejection (<3 months after treatment: days 1, 4, 5, 36, and 81, respectively), and in the sixth patient, the pancreas was lost 2 months after the first follow-up CAG (at 2 years) but 3 years before the second follow-up CAG 2 years later (see above). For most of their follow-up, these six patients had a nonfunctioning pancreas graft; therefore, it is unlikely that the timing of pancreas loss has influenced the results. If anything, this possible influence leads to underestimation of the difference in progression between those with and those without a functioning pancreas graft and not to overestimation.

At baseline, a total of 127 lesions were identified in the 48 patients: 116 with 20–50% diameter stenosis, and 11 with 50% diameter stenosis. Eight patients had no lesion >20%. In the other patients, the number of lesions per patient varied from one to nine (mean 3.4). MSD varied between 2.11 and 3.89 mm (mean 3.03) and MOD varied between 0.91 and 3.59 mm (mean 2.06). The total number of lesions in the analyzed angiographic follow-up cohort was 86 (average 2.66 per patient). Baseline MSD and MOD values are provided in Table 1.

MSD loss (progression of diffuse coronary atherosclerosis) was 0.024 mm/year (SE 0.067) in patients with a functioning pancreas graft, compared with 0.044 mm/year (SE 0.038) in patients in whom the pancreas graft was lost (Fig. 2).

View larger version (8K): [in this window] [in a new window]   Figure 2— Change in average MSD in mm/year ± SEM related to functional status of the pancreas graft. Vessel diameter loss (progression) is almost doubled in patients without functioning pancreas grafts as compared with patients with functioning pancreas graft.

Although the observed progression, on average, was almost doubled in patients in whom the pancreas graft was lost compared with patients with a functioning pancreas graft, this difference did not reach statistical significance, as expected given the observational character of the study and the relatively small number of patients. Figure 3 displays the individual changes in MSD (MOD changes yielded similar results). It is interesting to note that in the patients with a functioning pancreas graft, 10 of 26 patients (38%) have a negative change in MSD, i.e., regression of coronary atherosclerosis, whereas none of the patients in whom pancreas function was lost showed a tendency to regression. This difference in the amount of cases tending to regression is statistically significant (P = 0.035).

View larger version (10K): [in this window] [in a new window]   Figure 3— Change in MSD depicted per individual patient related to pancreas graft function. Note that in the patients with a functioning pancreas graft, 10 of 26 patients (38%) have a "negative loss" in MSD, i.e., regression of coronary atherosclerosis, whereas none of the 6 cases in whom pancreas function was lost showed a tendency to regression (P = 0.035).

Based on our results, a clinical trial comparing SPK and KTA, which probably will never take place because of the ethical and practical problems involved, would require 80 patients per group to reach, with 80% power, statistically significant results, showing that SPK is superior to KTA with regard to progression of coronary atherosclerosis.

	CONCLUSIONS

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
Vascular disease remains the major cause of both morbidity and mortality after transplantation in diabetic recipients (18–20). Therefore, for patients undergoing SPK, the potential benefits of normoglycemia are of great importance. Because SPK has been performed on a larger scale for only 10 years, data with respect to the long-term benefits concerning diabetic complications are very limited. Unfortunately, an extended period of exposure to hyperglycemia with its adverse sequelae, such as retinopathy, neuropathy, and life-shortening atherosclerosis, is likely to be in more advanced stages before the patient presents for a transplant (4,21,22). Although initial (functional) abnormalities are reversible with correction of hyperglycemia, later, more structural changes such as capillary sclerosis or retinal neovascularization are not. The best one could hope for would be that further changes in vascular structural abnormalities would be prevented by normoglycemia.

Pancreas transplantation seems to have little demonstrated benefit for established diabetic retinopathy, largely because most patients receiving a combined transplant have advanced eye disease (23–25). Presumably, pancreas transplantation was performed too late to be of benefit for retinopathy.

The influence of improved glycemic control on the progression of neuropathy is somewhat more encouraging (26–32). Stabilization of neuropathy seems feasible.

As stated, vascular disease remains the major cause of both morbidity and mortality after transplantation in diabetic recipients (18–20). In an individual patient, the risk of sustaining vascular complications is related to the degree of vascular disease before transplantation (20,33). When coronary angiography is performed before transplantation, patients found to have one or more coronary artery stenoses >50% have a 55% risk of sustaining a vascular event within 3 years of transplantation, independent of the type of transplant (20). For these reasons, it is of great importance to know whether pancreas transplantation might decrease progression of (coronary) atherosclerosis with its subsequent clinical events.

However, virtually no data on this topic are available. Our study provides unique material and supports the concept that in patients who have undergone SPK, progression of coronary atherosclerosis in patients with a functioning pancreas graft is reduced, compared with patients in whom the pancreas graft has failed. Furthermore, La Rocca et al. (34) described that carotid atherosclerotic lesions documented with carotid ultrasound continue to progress in both patients who have undergone SPK and those who have undergone KTA, but that progression was faster in patients with poor glycemic control. This is comparable with what we found in the coronary arteries with angiography. Possibly due to these beneficial effects of SPK, it has been described that left ventricular function seems to improve to a greater degree after a successful SPK than with KTA (35).

It is interesting to note that the beneficial effects of a functioning pancreas graft on progression of coronary atherosclerosis are at least as large as the effects of statin therapy in lipid-lowering trials such as the Regression Growth Evaluation Statin Study (REGRESS), which did not include type 1 diabetic patients, and that even perhaps SPK, like the statins, is capable of inducing regression of coronary atherosclerosis in a non-neglectable proportion of cases (11).

The pathogenesis of atherosclerosis is complex. Hyperglycemia is believed to contribute to atherosclerotic plaque formation in a number of ways, including glycation of collagen, alteration of endothelial cell function, glycoxidation of LDL cholesterol, and increased platelet reactivity (36,37). Therefore, SPK might, apart from slowing down progression of coronary atherosclerosis, also stabilize atherosclerotic plaques, restore endothelial reactivity, and reverse functional changes, thereby reducing clinical atherosclerotic events as well, as has been postulated for lipid-lowering studies with HMG-CoA reductase inhibitors, which were not prescribed yet at large scale to our study population during the study period.

Recognizing the limitations caused by the obligatory observational character of our study and the relatively small number of patients, it can be concluded that now, for the first time, evidence exists that after SPK, progression of coronary atherosclerosis in patients with a functioning pancreas graft is reduced, compared with patients in whom the pancreas graft has failed.

Our observation is an important part of the explanation for improved mortality rates reported in type 1 diabetic patients with end-stage renal failure after SPK compared with KTA (38–40).

Therefore, although a functioning pancreas transplant is associated with increased perioperative morbidity, normalization of blood glucose levels by SPK may indeed reduce progression of coronary atherosclerosis in type 1 diabetic patients and, in this way, improve clinical outcome as well as result in improved quality of life and stabilization of neuropathy. In light of the findings described above, SPK must be carefully considered for all diabetic transplant candidates.

	Acknowledgments

 
Dr. Jukema is an established clinical investigator of the Netherlands Heart Foundation (2001D032).

	Footnotes

 
Address correspondence and reprint requests to J. Wouter Jukema, MD, PhD, FESC, FACC, Head, Interventional Cardiology, Leiden University Medical Center, Department of Cardiology, C5-P, P.O. Box 9600, 2300 RC Leiden, the Netherlands. E-mail: j.w.jukema{at}lumc.nl.

Received for publication 30 August 2001 and accepted in revised form 11 February 2002.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

	References

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 

1. World Health Organization: Diabetes Mellitus: Report of a WHO Study Group. Geneva, World Health Org., 1985 (Tech. Rep. Ser., no. 727)
   
2. Manske CL, Wang Y, Rector TH, Wilson RF, White CW: Coronary revascularisation in insulin-dependent diabetic patients with chronic renal failure. Lancet 340:998–1000, 1992[Medline]
   
3. The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986, 1993[Abstract/Free Full Text]
   
4. Nathan DM: Long-term complications of diabetes mellitus. N Engl J Med 328:1676–1685, 1993[Free Full Text]
   
5. Landgraf R: Impact of pancreas transplantation on diabetic secondary complications and quality of life. Diabetologia 39:1415–1424, 1996[Medline]
   
6. Manske CL: Risks and benefits of kidney and pancreas transplantation for diabetic patients. Diabetes Care 22:B114–B120, 1999
   
7. Buchwald H, Matts JP, Fitch LL, for the Program on the Surgical Control of the Hyperlipidemias (POSCH) Group: Changes in sequential coronary arteriograms and subsequent coronary events. JAMA 268:1429–1433, 1992[Abstract]
   
8. Waters DW, Craven TE, Lespérance J: Prognostic significance of progression of coronary atherosclerosis. Circulation 87:1067–1075, 1993[Abstract/Free Full Text]
   
9. Azen SP, Mack WJ, Cashin-Hemphill L, LaBree L, Shircore AM, Selzer RH, Blankenhorn DH, Hodis HN: Progression of coronary artery disease predicts clinical coronary events. Circulation 93:34–41, 1996[Abstract/Free Full Text]
   
10. Smets YFC, van der Pijl JW, van Dissel JT, Ringer J. de Fijter JW, Lemkes HHPJ: Infectious disease complications of simultaneous pancreas kidney transplantation. Nephrol Dial Transplant 12:764–771, 1997[Abstract/Free Full Text]
    
11. Jukema JW, Bruschke AVG, van Boven AJ, Reiber JHC, Bal ET, Zwinderman AH, Jansen H, Boerma GJM, van Rappard FM, Lie KI: Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels: the "regression growth evaluation statin study (REGRESS). Circulation 91:2528–2540, 1995[Abstract/Free Full Text]
    
12. Reiber JHC, Jukema JW, Koning G, Bruschke AVG: Quality control in quantitative coronary arteriography. In Lipid Lowering Therapy and Progression of Coronary Atherosclerosis. Bruschke AVG, Lie KI, Reiber JHC, Wellens HJJ, Eds. Dordrecht, Kluwer Academic Publishers, 1996, p. 45–63
    
13. Reiber JHC, Jukema JW, Hekking E, van Houdt RM, Lie KI, Bruschke AVG: Catheter sizes for quantitative coronary arteriography. Cathet Cardiovasc Diagn 33:153–155, 1994[Medline]
    
14. Jukema JW, van Boven AJ, Zwinderman AH, Bal ET, Reiber JHC, Bruschke AVG: The influence of angiographic endpoints on the outcome of lipid intervention studies: a proposal for standardization. Angiology 47:633–642, 1996
    
15. Bruschke AVG, Jukema JW, van Boven AJ, Bal ET, Reiber JHC, Zwinderman AH: Angiographic endpoints in progression trials. In Lipid Lowering Therapy and Progression of Coronary Atherosclerosis. Bruschke AVG, Lie KI, Reiber JHC, Wellens HJJ, Eds. Dordrecht, Kluwer Academic Publishers, 1996, p. 71–77
    
16. Jukema JW, Bruschke AVG, Reiber JHC: Lessons learned from angiographic coronary atherosclerosis trials. In Cardiovascular Imaging. Reiber JHC, van der Wall EE, Eds. Dordrecht, Kluwer Academic Publishers, 1996, p. 119–132
    
17. Pitt B, Mancini GBJ, Ellis SG, Rosman HS, J-S Park, McGovern ME, for the PLAC I investigators: Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. J Am Coll Cardiol 26:1133–1139, 1995[Abstract]
    
18. Douzdjian V, Abecassis MM, Corry RJ, Hunsicker LG: Simultaneous pancreas-kidney versus kidney-alone transplants in diabetics: increased risk of early cardiac death and acute rejection following pancreas transplants. Clin Transplant 8:246–251, 1994[Medline]
    
19. Bruce DS, Newell KA, Woodle ES, Millis JM, Piper JB, Seaman DS, Huss E, Thislewaite JR: Late complications in kidney-pancreas transplant recipients. Transplant Proc 27:3118, 1995[Medline]
    
20. Manske CI, Wilson FR, Wang Y, Thomas W: Atherosclerotic vascular complications in diabetic transplant recipients. Am J Kidney Dis 29:601–607, 1997[Medline]
    
21. Hansen KF, Dahl-Jorgensen K, Lauritzen T, Feldt-Rasmussen B, Brinchmann-Hansen O, Deckert T: Diabetic control and microvascular complications: the near normoglycemaemic experience. Diabetologia 29:677–684, 1986[Medline]
    
22. Krolewski AS, Warram JH, Freire MBS: Epidemiology of late diabetic complications. Endocrinol Metab Clin North Am 25:217–242, 1996[Medline]
    
23. Ramsay RC, Goetz FC, Sutherland DER, Mauer SM, Robison LL, Cantrill HL, Knobloch WH, Najarian JS: Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus. N Engl J Med 318:208–214, 1988[Abstract]
    
24. Schmidt D, Kirste G, Schrader W: Progressive proliferative diabetic retinopathy after transplantation of the pancreas. Acta Ophthalmol 72:743–751, 1994
    
25. Wang Q, Klein R, Moss SE, Klein BEK, Hoyer BS, Burke K, Sollinger HW: The influence of combined kidney-pancreas transplantation on the progression of diabetic retinopathy. Ophthalmology 10:1071–1076, 1994
    
26. Solders G, Wilczek H, Gunnarsson R, Tyden G, Persson A, Groth CG: Effects of combined pancreatic and renal transplantation or diabetic neuropathy: a two-year follow-up study. Lancet i:1232–1235, 1987
    
27. Kennedy WR, Navarro X, Goetz FC, Sutherland DER, Najarian JS: Effects of pancreatic transplantation on diabetic neuropathy. N Engl J Med 322:1031–1037, 1990[Abstract]
    
28. Muller-Felber W, Landgraf R, Scheuer R, Wagner S, Reimers CD, Nusser J, Abendroth D, Illner WD, Land W: Diabetic neuropathy 3 years after successful pancreas and kidney transplantation. Diabetes 42:1482–1486, 1993[Abstract]
    
29. Trojaborg W, Smith T, Jakobsen J, Rasmussen K: Effect of pancreas and kidney transplantation on the neuropathic profile in insulin-dependent diabetics with end-stage nephropathy. Acta Neurol Scand 90:5–9, 1994[Medline]
    
30. Solders G, Tyden G, Tibell A, Persson A, Groth CG: Improvement in nerve conduction 8 years after combined pancreatic and renal transplantation. Transplant Proc 27:3091, 1995[Medline]
    
31. Allen RD, AL-Harbi IS, Morris JG, Clouston PD, O’Connell PJ, Chapman JR, Nankivell BJ: Diabetic neuropathy after pancreas transplantation determinants of recovery. Transplantation 63:830–838, 1997[Medline]
    
32. Martinenghi S, Comi G, Galardi G, Di Carlo V, Pozza G, Secchi A: Amelioration of nerve conduction velocity following simultaneous kidney/pancreas transplantation is due to the glycemic control provided by the pancreas. Diabetologia 40:1110–1112, 1997[Medline]
    
33. Lemmers MJ, Barry JM: Major role for arterial disease in morbidity and mortality after kidney transplantation in diabetic recipients. Diabetes Care 14:295–301, 1991[Abstract]
    
34. La Rocca E, Minicucci F, Secchi A, Cirulino D, Boniatti D, Ferrani G, Castoldi R, DiCarlo V, Pozz G: Evolution of carotid vascular lesions in kidney-pancreas and kidney-alone transplanted insulin-dependent diabetic patients. Transplant Proc 27:3072, 1993
    
35. Gaber AO, El-Gebely S, Sugathan P, Elmer DS, Hathaway DK, McCully RB, Shokouh-Anuru MH, Burlew BS: Early improvement in cardiac function occurs for pancreas-kidney but not diabetic kidney-alone transplant recipients. Transplantation 59:1105–1112, 1995[Medline]
    
36. Tooke JE: Microvascular function in human diabetes: a physiological perspective. Diabetes 44:561–564, 1995[Abstract]
    
37. Brownlee M, Cerami A, Vlassara H: Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 318:1315–1321, 1988[Medline]
    
38. Secchi A, Caldara R, La Rocca E, Fiorina P, De Carlo V: Cardiovascular disease and neoplasms after pancreas transplantation (Letter). Lancet 352:65, 1998
    
39. Smets YFC, Westendorp RGJ, van der Pijl JW, de Charro F Th, Ringers J, de Fijter JW, Lemkes HHPJ: Effect of simultaneous pancreas-kidney transplantation on mortality of patients with type-1 diabetes mellitus and end-stage renal failure. Lancet 353:1915–1919, 1999[Medline]
    
40. Ojo AO, Meier-Kreische H-U, Hanson JA, Leichtman A, Magee JC, Cibrik D, Wolfe RA, Port FK, Agodoa L, Kaufman DB, Kaplan B: The impact of simultaneous pancreas-kidney transplantation on long-term patient survival. Transplantation 71:82–90, 2001[Medline]
    

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				R. John, K. Lietz, S. Huddleston, A. Matas, K. Liao, S. Shumway, L. Joyce, and R. M. Bolman Perioperative outcomes of cardiac surgery in kidney and kidney pancreas transplant recipients J. Thorac. Cardiovasc. Surg., May 1, 2007; 133(5): 1212 - 1219. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Transplantation and Islet Topics Diabetes Care, January 1, 2005; 28(1): 213 - 219. [Full Text] [PDF]

				F. Zaman, K. D. Abreo, S. Levine, W. Maley, and G. B. Zibari Pancreatic Transplantation: Evaluation and Management J Intensive Care Med, May 1, 2004; 19(3): 127 - 139. [Abstract] [PDF]

				R. P. Robertson Islet Transplantation as a Treatment for Diabetes -- A Work in Progress N. Engl. J. Med., February 12, 2004; 350(7): 694 - 705. [Full Text] [PDF]

				R. J. T. Owen, E. A. Ryan, K. O'Kelly, J. R. T. Lakey, M. C. McCarthy, B. W. Paty, D. L. Bigam, N. M. Kneteman, G. S. Korbutt, R. V. Rajotte, et al. Percutaneous Transhepatic Pancreatic Islet Cell Transplantation in Type 1 Diabetes Mellitus: Radiologic Aspects Radiology, October 1, 2003; 229(1): 165 - 170. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jukema, J. W. Articles by de Fijter, J. W. Search for Related Content PubMed PubMed Citation Articles by Jukema, J. W. Articles by de Fijter, J. W. Social Bookmarking                What's this?