Pancreatic transplantation: Brief review of the current evidence

Table 1 Comparison of criteria of type 1 and type 2 diabetes mellitus[4]

	Type 1 diabetes	Type 2 diabetes
Prevalence	Common, increasing	Increasing
Age at presentation	Throughout childhood	Puberty
Onset	Typically, acute severe	Insidious to severe
Ketosis at onset	Common	5% to 10%1
Affected relative	5% to 10%	75% to 90%
Female: male	1:1	Approximately 2:1
Inheritance	Polygenic	Polygenic
HLA-DR3/4	Strong association	No association
Ethnicity	Most common in non- Hispanic white	All2
Insulin secretion	Decreased/absent	Variable
Insulin sensitivity	Normal when controlled	Decreased
Insulin dependence	Permanent	Variable
Obese or overweight	20% to 25% overweight3	> 80% obese
Acanthosis nigricans	12%4	50% to 90%4
Pancreatic antibodies	Yes5	No6

¹Reported frequency of ketonuria or ketoacidosis at time of diagnosis of type 2 diabetes mellitus (T2DM) varies widely.

²In North America, T2DM predominates in native America, African-American, Hispanic, Canadian First Nation, Pacific Islander, and Asian-American youth.

³With increased prevalence of childhood overweight, 20% to 25% of newly diagnosed with type 1 diabetes mellitus (T1DM) are overweight, which is higher than the prevalence of overweight in a similar population without T1DM. However, the prevalence of obesity is not increased among children and adolescents with T1DM. Recent weigh loss is common at presentation of children with T1DM, including among those who are overweight or obsess.

⁴These frequencies of acanthosis nigricans are based on a registry study in the United States. Populations with lower rates of obesity or difference ethnic mixes may have different results.

⁵Autoantibodies to insulin (IAA), islet cell cytoplasm (ICA), glutamic acid decarboxylase (GAD), tyrosine phosphatase (insulinoma associated) antibody (IA-2 and IA-2β), or zine channel antibody (ZnT8) are present at diagnosis in 85% to 89% of patients with T1DM.

⁶One study reported that 9.8% of youth with phenotypic T2DM have pancreatic antibodies to IA-2 and/or GAD. HLA: Human leukocyte antigen.

Table 2 Kidney transplant graft failure rates associated with simultaneous pancreas-kidney and pancreas after kidney[8]

Type of the allograft	1 yr	5 yr	10 yr
SPK	3.1%	16.5%	37.7%
PAK (deceased donor)	3.3%	21.2%	51.2%
PAK (living donor)	3.0%	13.7%	37.0%

SPK: Simultaneous pancreas-kidney; PAK: Pancreas after kidney.

Table 3 Sample of studies evaluating the effect of pancreatic transplantation on the complications of diabetes mellitus

Ref.	Patient cohorts	Outcomes of interest	Time after transplant (yr)	Results
Cardiovascular disease
Fiorina et al[9], 2000	SPK (n = 42) vs KTA (n = 26) vs type 1 diabetes (n = 20)	Left ventricular systolic and diastolic function assessed by radionuclideventriculography	4 yr	Left ventricular ejection fraction was higher in SPK recipients than in KTA recipients [75.7 (SD 1.8%) vs 65.3% (2.8%); P = 0.02] and type 1 diabetes controls (75.7 (1.8%) vs 61.2 (3.7%); P = 0.004).
Biesenbach et al[10], 2005	SPK (n = 12) vs KTA (n = 10)	Composite endpoint of myocardial infarction, stroke, and amputation	10 yr	Lower incidence of myocardial infarction (16% vs 50%), stroke (16% vs 40%), and amputations (16% vs 30%) in SPK vs KTA recipients (P < 0.05 for composite endpoint of all three events)
Diabetic nephropathy
Fioretto et al[11], 1998	PTA: Pre-transplant vspost-transplant (n = 8)	Native kidney biopsy:structural morphology	10 yr	Improvement in glomerular basement membrane thickening, tubular basement membrane thickening, and mesangial expansion after transplantation compared with before
		before and after transplant
Boggi et al[12], 2011	PTA: Pre-transplant vs post-transplant (n = 71)	Proteinuria and estimatedGFR (eGFR)	Up to 4 yr	Overall, proteinuria decreased from 1.36 (SD 2.72) g/d pre-transplant to 0.29 (0.51) g/d post-transplant (P < 0.01) eGFR decreased by about 20% from 94 (39) mL/min per 1.73m2 to 75 (22) mL/min per 1.73 m2 (P < 0.01)
Diabetic neuropathy
Havrdova et al[13], 2016	SPK: Pre-transplant vspost-transplant (n = 12)	Epidermal nerve fiberdensity on skin biopsy, autonomic function tests, and nerve conduction studies	Up to 8 yr	No improvement in epidermal nerve fiber density or functional deficits on autonomic function tests
Boggi et al[12], 2011	PTA: Pre-transplant vspost-transplant (n = 71)	Clinical neurologicexamination (vibration threshold), nerve conduction studies, and autonomic function tests (lying-to-standing test)	Up to 4 yr	Significant improvement in mean vibration thresholds, nerve conduction studies, and autonomic function tests after PTA compared with before
Diabetic retinopathy
Boggi et al[12], 2011	PTA: Pre-transplant vs post-transplant (n = 71)	Visual acuity scores andfundoscopic examination	Up to 4 yr	Before transplantation, 7.5% of patients had no retinopathy and remained lesion-free at 4 yr. Of the 29.5% with non-proliferative retinopathy, 75% improved and 25% remained unchanged. In the remainder with proliferative retinopathy, lesions remained stable in 82% and progressed in 18%
Giannarelli et al[14], 2006	PTA (n = 33) vs type 1 diabetes (n = 35)	Visual acuity scores, fundoscopic examination, and angiography in selected cases	Up to 30 mo	Before transplant, 9% of patients with PTA and 6% of those with type1 diabetes had no retinopathy, 24% and 29% had non-proliferative retinopathy, and 67% and 66% had proliferative retinopathy. Overall, the percentage of patients with improved or stabilized retinopathy was significantly higher in the PTA group (P < 0.01)
Koznarova et al[15], 2000	SPK (n = 43) Vs KTA (n = 45)	Visual acuity scores and fundoscopic examination	3 yr	In the SPK group, fundoscopic findings at the end of follow-up had improved, stabilized, or deteriorated in 21.3%, 61.7%, and 17.0%, respectively. In the KTA group these figures were 6.1 %, 48.8%, and 45.1% (P < 0.001)

KTA: Kidney transplant alone; SPK: Simultaneous pancreas-kidney; PAK: Pancreas after kidney.

Table 4 Complications of pancreatic transplantation[19]

Complications
Early complications
Allograft parenchymal complications	Acute pancreatitis
	Necrotizing pancreatitis
	Fistulous tracts
Infection and abscesses
Entric complications	Anastomosis leakage at duodeno-enterostomy
	Ileus Colonic infection.
Vascular complications	Venous or arterial graft thrombosis
	Acute bleeding
Late complications
Allograft parenchymal complications	Rejection
	Pseudocyst formation
	Post-transplant lymphoproliferative disease
Enteric complications	Small bowel obstruction
	Colonic infection
Vascular complications	Arterial or venous pseudoaneurysms