Diabetes is one of the most common chronic diseases in nearly all countries and continues to increase in number and significance [24, 25]. The International Diabetes Federation reports that the current prevalence of diabetes among adults aged 20–79 years in the world is of around 8 %, corresponding to more than 380 million people, increasing to 592 million people in 2035, in accordance with recent estimations [25]. The disease can be diagnosed by the use of the following criteria [24]: (a) presence of classic symptoms of hyperglycaemia or hyperglycaemic crisis and a random plasma glucose value ≥200 mg/dl (11.1 mmol/l); (b) fasting plasma glucose (FPG) value ≥126 mg/dl (7.0 mmol/l), with fasting defined as no caloric intake for at least 8 h before the test; (c) glycated haemoglobin (HbA1c) value ≥6.5 % [provided the test is performed in a laboratory using a method that is National Glycohemoglobin Standardization Program (NGSP) certified and standardized to the Diabetes Control and Complications Trial (DCCT) assay]; (d) 2-h plasma glucose level ≥200 mg/dl (11.1 mmol/l) during an oral glucose tolerance test (OGTT), using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. In the absence of clear symptoms of hyperglycaemia, criteria (b) to (d) should be confirmed by repeat testing. In addition, three categories of increased risk for diabetes have been identified: impaired fasting glycaemia (IFG) for FPG values of 100–125 mg/dl (5.6–6.9 mmol/l); impaired glucose tolerance (IGT), for 2-h plasma glucose on the 75-g OGTT between 140 and 199 mg/dl (7.8–11.0 mmol/l); and the situation when HbA1c value is 5.7–6.4 % [24]. For all these three conditions, risk is continuous, extending below the lower limit of the range and becoming greater at higher ends of the range [24]. On the basis of aetiology and clinical presentation, diabetes is classified into four types: type 1 (caused by autoimmune destruction of the insulin-producing beta-cells in the pancreas and representing 5–10 % of all cases), type 2 (characterized by relative insulin deficiency and insulin resistance, very often associated with obesity, and accounting for approximately 90 % of cases), gestational diabetes (with onset or first recognition during pregnancy), and an heterogenous group identified as other specific types that includes forms due to monogenic defects leading to beta-cell failure, genetic defects in insulin action, diseases of the exocrine pancreas, endocrinopathies, drugs or chemicals, infections, uncommon forms of autoimmunity, and other genetic syndromes sometimes associated with diabetes [24].

Diabetes is associated with high morbidity and increased mortality [24, 25]. The disease enhances the risk of heart disease and stroke two- to fourfold, and 50–70 % of people with diabetes die of these events. Diabetic retinopathy is a major cause of blindness that occurs in approximately 2 % of patients after 15 years of diabetes; moreover, about 40–50 % of patients develop severe visual impairment over the years. Despite improved therapies, diabetes remains the leading cause of kidney failure, and 10–20 % of people with diabetes die of kidney failure (see also below). Diabetic neuropathy, in one or more of its several forms, affects up to 50 % of people with diabetes, and in combination with reduced blood flow, neuropathy in the feet increases up to 25-fold the chance of foot ulcers and eventual limb amputation severalfold. Finally, close to four million deaths in the 20–79 age group may be attributable to diabetes in 2010, and the proportion of deaths due to diabetes in people under 60 years of age was close to 50 % in 2013 [25].

It is accepted that 20–40 % of diabetic patients develop diabetic nephropathy over a period of 25 years from the diagnosis of disease, and 5–15 % progress to ESRD [24, 25]. Persistent albuminuria in the interval of 30–299 mg/24 h is considered an early stage of diabetic nephropathy in type 1 diabetes and a marker for development of nephropathy in type 2 diabetes [24]. Although evidence has been provided to show spontaneous remission of albuminuria in this category (up to 40 %) or stabilization without progressing to more elevated levels of albuminuria (≥300 mg/24 h) over 5–10 years of follow-up (30–40 %), the remaining patients will tend to move to the more significant levels of ≥300 mg/24 h and will be likely to progress to ESRD [24]. These patients will ultimately require life-sustaining, long-term renal replacement therapy, either in the form of dialysis or kidney transplantation. In the presence of type 1 diabetes, and in selected cases of type 2 diabetes, patients could benefit of a kidney-pancreas transplantation. The first kidney and pancreas transplant was performed in 1966 by William Kelly and Richard Lillehei at the University of Minnesota, USA [26]. Since then, more than 40,000 pancreas transplants have been performed worldwide [27]. Of them, >80 % have been done in patients with kidney failure who therefore have undergone a simultaneous pancreas-kidney (SPK) transplantation. In approximately 10 % of cases, a kidney transplant has been performed first, followed by a pancreas after kidney transplant (PAK) because of poor glycaemic control or progression of chronic vascular diabetic complications, including the possible development of diabetic nephropathy in the transplanted kidney. In many cases (75 % in 2012), recipients of a PAK have first undergone a living donor kidney transplant [27]. The remaining 8–10 % of pancreas transplants (pancreas transplant alone, PTA) have been done in diabetic patients with preserved renal function, but experiencing extreme diabetes instability and/or progressive vascular diabetes complications [28, 29]. In PTA, patients may develop end-stage renal disease due to the nephrotoxic effects of immunosuppressive drugs (calcineurin inhibitor in particular), which, in turn, may lead to a subsequent kidney transplantation (around 6 % at 5 years) [29]. Renal function before PTA is a strong predictor of end-stage renal disease after PTA, with cumulative risk at 10 years increasing from 21.8 % with pre-PTA estimated glomerular filtration rate (eGFR) of ≥90 ml/min/1.73 m² to 52.2 % with eGFR <60 ml/min/1.73 m² [30]. In the SPK and PTA categories, 1- and 5-year patient survival is of around 95 % and >80 %, respectively, and the corresponding kidney graft survivals are of approximately 95 % (1 year) and 80 % (5 years) [27]. The current 1- and 5-year survival rates for the pancreatic graft are 89 and 71 % in SPK, 86 and 65 % in PAK, and 82 and 58 % in PTA, with a clear trend to further improvements [27, 28, 31–33].

Since kidney-pancreas transplantation has beneficial effects on life expectancy, course of microvascular and macrovascular diabetes complications, and quality of life [27, 28, 31–33], the procedure is indicated in type 1 diabetic patients with end-stage renal disease (on dialysis or in the pre-emptive stage), in whom the risks of surgery and immunosuppression are deemed acceptable and lower than those of dialysis therapy and scarcely effective insulin therapy. Selected type 2 diabetic patients (not obese, with progressive vascular diabetic complications) can also be considered [27–29, 34]. Indications and admission criteria for kidney-pancreas transplantation in our centre, which are based on available evidence [27–29, 31–34], are as follows: end-stage renal disease (on haemodialysis or peritoneal dialysis) and type 1 diabetes [selected type 2 diabetic patients (not obese and with chronic diabetes vascular complications) may also be considered]; chronic renal failure (before dialysis – pre-emptive – with measured LOW glomerular filtration rate) and type 1 diabetes [selected type 2 diabetic patients (not obese and with chronic diabetes vascular complications) may also be considered]; severe nephrotic syndrome and type 1 diabetes [selected type 2 diabetic patients (not obese and with chronic diabetes vascular complications) may also be considered]; acceptable surgical and immunosuppressive therapy risks; appropriate psychosocial attitudes; age <60 years; the absence of additional exclusion criteria. The latter that may be permanent or temporary include HIV positivity [with the exception of admission in specific protocols [35]], neoplasms (also depending on tumour type and biology, activity, clinical and pathologic stage, duration of disease-free period), infections, severe heart diseases and/or polidistrectual atherosclerosis, severe chronic respiratory failure, liver failure, uncorrectable urinary tract abnormalities, bilateral iliac vein thrombosis, chronic coagulopathies, psychiatric diseases, mental retardation, drug addiction (including chronic ethylism), and severe obesity.

The University of Wisconsin solution, originally developed as a preservation solution for pancreas transplantation [46], remains the “gold standard” for preservation of pancreas grafts. HTK [47] and Celsior [48] solutions, originally developed for cardioplegia, are also used for pancreas preservation. If cold ischaemia is maintained within 12 h, pancreas grafts are preserved equally well irrespective of the type of preservation solution.

Pancreas retrieval is usually performed in multiorgan donors. All suitable donors should be pancreas donors, irrespective of variations in hepatic vasculature. Exceptions to this rule can occur because of special needs of the liver recipient or organizational issues.

Techniques for pancreas procurement can be summarized into two main strategies: quick en bloc procurement after minimal normothermic dissection [49] and extensive warm dissection followed by individual graft retrieval [50]. The first technique is mandatory if the donor in unstable and is often preferred because of limited graft manipulation and lower risk of iatrogenic injury to both the pancreas and hepatic vasculature [49].

As previously mentioned, pancreas inspection and quality of visceral perfusion play a major role in determining pancreas suitability for transplantation. Grafts with fibrosis and/or calcification, intralobular fat, and severe oedema should be discarded.

With few exceptions, pancreas allografts are composed by the entire pancreas plus a duodenal segment. At the back table, the pancreas graft must be carefully prepared by cleaning excessive fat, preparing vascular pedicles, trimming duodenal segment, and removing the spleen.

Since the celiac trunk and the hepatic artery go with the liver, creation of a single anastomotic pedicle requires the use of a Y-bifurcated iliac graft, made of common, external, and internal donor iliac arteries. The peripheral branches of the Y-shaped graft are anastomosed end-to-end to the stumps of the superior mesenteric artery and the splenic artery. Despite the patency of one of these two large arteries that is usually sufficient to supply the entire pancreas graft and duodenal segment, variations in the origin of the dorsal pancreatic artery and intraparenchymal vasculature can produce segmental graft infarction after occlusion of one large arterial pedicle. To verify the presence of valid collateral circulation, a small amount of preservation solution can be injected in one of the two arteries. Brisk backflow from the other arterial pedicle, as well as outflow from the portal vein, indicates satisfactory collateral circulation. The absence of arterial backflow requires revascularization of the gastroduodenal artery [51].

The duodenal segment is trimmed at the appropriate length and closed by a stapler. Closures are reinforced and inverted. We prefer to place a Foley catheter in the duodenal segment to provide temporary drainage of pancreatic juice after reperfusion in order to avoid duodenal overdistension [49].

Most of the surgical challenges associated with pancreas transplantation revolve around the high risk of vascular thrombosis and the difficult management of exocrine secretions. Despite improved results, no surgical technique, and even no single surgical step, has achieved universal acceptance [52]. The incision is usually a midline laparotomy, but the two grafts can also be transplanted through two separate iliac, hockey stick, incisions. The graft can be placed “head up” or “head down”, in the pelvis, right flank region, or over the mesenteric root. Venous effluent can be achieved either in the portal or systemic circulation.

Typically, the pancreas is transplanted on the right side, because of the more convenient venous anatomy, and the kidney on the left iliac fossa. Ipsilateral SPK transplantation can also be accomplished, to spare one iliac axis or because of specific recipient needs. Exocrine secretions can be drained in the bladder or in the gut. Enteric drainage occurs in the small bowel either directly or through a Roux-en-Y loop. Newer techniques include direct anastomosis with recipient duodenum [53] or stomach [54]. Alleged advantages of these methods include direct access to donor duodenum for endoscopic biopsy, but concerns remain on safety, especially when recipient duodenum is involved, if allograft pancreatectomy becomes necessary.

Recently, we have described the technique for laparoscopic robot-assisted, pancreas transplantation including SPK transplantation [55, 56]. The advantages of a minimally invasive approach would seem obvious in the fragile diabetic recipient, but safety and efficacy of this newer technique need to be further assessed.

Kidney transplantation employs standard techniques, but if performed through a transperitoneal approach, the graft should be fixed in order to avoid twisting around the renal pedicle [57].

Cold ischaemia time exceeding 20 h has long been recognized a negative prognostic factor for the occurrence of surgical complications after pancreas transplantation. A growing burden of evidence shows that cold ischaemia time should actually be reduced to 12 h or less, especially when using less than ideal donors [43].

Despite recent improvements, the results of pancreas transplantation continue to be challenged by high rejection rates [58]. Because of this concern, the use of T-cell depleting antibody induction is often employed.

Maintenance immunosuppression regimens are based on steroids, tacrolimus, and mycophenolate in more than 80 % of cases [59, 60]. The switching to cyclosporine and/or mammalian target of rapamycin is considered to reverse the side effects related to the standard regimen or under individual circumstances [61, 62].

After the transplant, recipients are monitored in the postanaesthesia care unit or intensive care unit. Ventilatory and haemodynamic assessment is paramount during recovery. A complete blood count, complete chemistry, coagulation profiles, chest radiograph, and EKG are routinely obtained. Vital signs, oxygen saturation, and urine output are checked frequently. The first 24–48 h posttransplant is of overwhelming importance.