Pancreatogenic Diabetes after Pancreatic Resection

Review Published online: July 5, 2011

Pancreatology 2011;11:268–276 DOI: 10.1159/000328785

Pancreatogenic Diabetes after Pancreatic Resection Hiromichi Maeda a, b Kazuhiro Hanazaki a  

a

 

Department of Surgery, Kochi University and b Department of Surgery, Kochi Prefectural Hata Kenmin Hospital, Nankoku City, Japan  

 

Key Words Pancreatogenic diabetes ⴢ Distal pancreatectomy ⴢ Pancreatoduodenectomy ⴢ Total pancreatectomy ⴢ Insulin ⴢ Glucagon ⴢ Pancreatic polypeptide

Abstract The loss of pancreatic parenchyma resulting from pancreatic resection causes an extreme disruption of glucose homeostasis known as pancreatogenic diabetes. This form of glucose intolerance is different from the other forms of diabetes mellitus in that affected individuals suffer frequent episodes of iatrogenic hypoglycemia. The development of sophisticated surgical procedures, improved postoperative care, and the capacity for early diagnosis of disease has prolonged life expectancy after pancreatic resection. For this reason, pancreatogenic diabetes is now attracting attention as the primary factor influencing quality of life in patients who have undergone this procedure. The incidence of newonset diabetes mellitus after pancreatic resection increases as the follow-up period after surgery becomes longer and is related to the progression of underlying disease, the type of surgery, and the extent of resection. The pathophysiology of pancreatogenic diabetes is related to pancreatic hormone deficiency and the altered responses of the liver and peripheral organs to lower than normal hormone levels. Hypergly-

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cemia occurs when the amount of insulin produced or administered is insufficient because of unsuppressed hepatic glucose production secondary to a deficiency in pancreatic polypeptide. In contrast, patients lapse into hypoglycemia when insulin is barely excessive because of enhanced peripheral insulin sensitivity and glucagon deficiency. Nutritional state, pancreatic exocrine function and intestinal function also affect glycemic control. Insulin replacement is considered to be the main treatment option for insulin dependent pancreatogenic diabetes. Pancreatic polypeptide replacement and islet autotransplantation have potential as new approaches to treating patients with pancreatogenic diabetes after pancreatic resection. Copyright © 2011 S. Karger AG, Basel and IAP

Introduction

Processes leading to diffuse destruction of the pancreas, such as pancreatic resection and chronic pancreatitis, result in pancreatic hormone deficiencies and altered responses of related organs to pancreatic hormones, thereby causing a type of impaired glucose metabolism known as pancreatogenic diabetes. The American Diabetes Association classifies this type of diabetes mellitus as ‘other specific type of diabetes mellitus’ [1].

Kazuhiro Hanazaki, MD, PhD Department of Surgery, Kochi Medical School Kochi University, Kohasu-Okocho Nankoku City 783-8505 (Japan) Tel. +81 88 880 2370, E-Mail hanazaki @ kochi-u.ac.jp

Pancreatogenic diabetes after pancreatic resection differs from type 1 and type 2 diabetes mellitus [1, 2]. Unlike type 1 diabetes mellitus, which is caused by cellular mediated autoimmune destruction of beta-cells of the pancreas and carries a high risk of hyperglycemia and ketoacidosis [1], pancreatogenic diabetes seldom causes ketoacidosis or severe hyperglycemia [2, 3]. Pancreatogenic diabetes is also unlike type 2 diabetes mellitus, which is characterized by insulin resistance and relative insulin deficiency, because patients with pancreatic diabetes are sensitive to insulin. Because of the increased peripheral sensitivity to insulin and the reduced glucagon level in pancreatogenic diabetes, exogenous insulin administration frequently causes hypoglycemic attacks, characteristically called ‘brittle’ diabetes. Iatrogenic hypoglycemia occasionally leads to hospitalization, irreversible damage to the central nervous system or even death [4–8]. Because glycemic control in these patients is clinically challenging, HbA1c is usually quite high [6] and nephropathy, neuropathy, and retinopathy can develop as a result of long-term inappropriate therapy [9]. Currently, surgical resection is being utilized more for benign pancreatic tumors due to diagnostic modalities and increased understanding of diseases, thus giving us new insights concerning postoperative diabetes. We will highlight the incidence of postoperative pancreatic diabetes, its pathophysiology, and possible treatments.

Distal Pancreatectomy In the clinical setting, a euglycemic patient with obesity and subclinical impaired glucose tolerance might develop overt diabetes mellitus after pancreatic resection because of preoperative insulin resistance and relative insulin deficiency. Therefore, this patient possesses the characteristic hormonal and clinical features of type 2 diabetes mellitus and not necessarily those of pancreatogenic diabetes. Thus, in order to properly diagnose pancreatogenic diabetes mellitus after pancreatic resection, it is necessary to measure the levels of pancreatic hormones and the degree of insulin sensitivity. There is no dispute that total pancreatectomy results in insulin-dependent pancreatogenic diabetes [4, 6, 8]. Other surgical procedures can result in the onset of diabetes mellitus, the rate of which appears to be related to progression of the underlying disease (reduction of islets cell reserve), duration of follow-up, extent of resection,

and type of surgery. Distal pancreatectomy is the resection of the tail and body of the pancreas, which volume of resection depends on the location of the responsible disease. Hutchins et al. [7] studied 90 patients undergoing distal pancreatectomy for chronic pancreatitis with a mean follow-up period of 34 months. The median pancreatic resection volume was 50% (range 10–90%) of the total volume. Of the 77 patients whose pancreatic endocrine functions were assessed, 7 had glucose intolerance, 8 had diabetes mellitus preoperatively, 18 (23%) showed diabetes mellitus immediately after pancreatic resection, and another 14 developed ‘delayed’ diabetes mellitus within a median period of 27 months from surgery to onset. Together with other clinical studies, these findings show that patients with chronic pancreatitis have a 25– 50% risk of developing diabetes mellitus shortly after distal pancreatectomy [7, 10, 11]. Malka et al. [12] prospectively studied 500 patients with chronic pancreatitis to elucidate risk factors associated with the onset of diabetes mellitus. Of these patients, 51% had undergone elective surgeries, such as pancreatic drainage, pancreatoduodenectomy and distal pancreatectomy, and the remaining 49% had not been operated on. The cumulative rate of the appearance of diabetes was 83 8 4% at 25 years after the onset of chronic pancreatitis. Univariate and time-dependent multivariate analysis identified the onset of pancreatic calcification and distal pancreatectomy as independent risk factors for diabetes mellitus and insulin dependency. However, the prevalence of diabetes mellitus did not increase in the surgical group overall, implying that the development of lateonset diabetes mellitus following pancreatic resection reflects the natural course of chronic pancreatitis rather than the operation itself. Compared with resection in treating chronic pancreatitis, resection of pancreatic tumors apparently has a lesser impact on endocrine function. A study of 235 patients with pancreatic diseases, including 23% with chronic pancreatitis and 77% with tumorous pancreatic disease, revealed the rate of new-onset diabetes mellitus after distal pancreatectomy to be approximately 8% [13]. King et al. [14] reported a similar result in a study of 125 patients who had undergone distal pancreatectomy, mainly for pancreatic neoplastic lesions. In their study, only 9% of previously nondiabetic patients developed diabetes mellitus during a median follow-up period of 21 months. The rate of new-onset diabetes mellitus after distal pancreatic resection in patients with presumably normal pancreatic parenchyma is unexpectedly low at approximately 5–9% [13–15].

Pancreatogenic Diabetes

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Incidence of Diabetes after Pancreatic Resection

(table 1)

269

Table 1. Incidence of postoperative diabetes mellitus

Surgery

Authors

Patients

Pathology

NO-DM

Follow-up

DP

Hutchins et al. [7] Schoenberg et al. [10] Lillemoe et al. [13]

90 74 235

32/77 (42%) 16/58 (28%) 19/235 (8%)

34 months (mean) 58 months (median)

King et al. [14]

125

10/111 (9%)

21 months (median)

Shoup et al. [15]

211

chronic pancreatitis chronic pancreatitis 24% chronic pancreatitis 76% tumors 8.8% chronic pancreatitis 92% tumors tumors

6/211 (5%)

21 months (median)

0/19 (0%) 2/26 (8%) 0/19 (0%)

55 months (median) 33 months (mean) 71 months (median)

CP

Adham et al. [22] Allendorf et al. [23] Sudo et al. [24]

50 26 19

tumors benign tumors benign tumors

DPPHR

Keck et al. [28]

92

chronic pancreatitis

34%/14% (Frey/Beger)

60 months (median)

PD

Traverso and Kozarek [29] Sakorafas et al. [31] Huang et al. [32]

chronic pancreatitis chronic pancreatitis 48% benign tumors 52% pancreatic cancer benign tumors

18/57 (32%) 48%* 13/49 (27%) 21/54 (39%) 9/51 (18%)

42 months (mean) 6.6 years (mean)

Falconi et al. [33] TP

Müller et al. [8]

57 105 103 51 147

various

47 months (median)

147/147 (100%)

not defined

NO-DM = New-onset diabetes mellitus; DP = distal pancreatectomy; CP = central pancreatectomy; DPPHR = duodenum-preserving pancreatic head resection; PD = pancreatoduodenectomy; TP = total pancreatectomy. * Preoperative evaluation identified diabetes in 8% of patients.

A key clinical observation is that preoperatively nondiabetic donors who undergo a hemi-pancreatectomy (a procedure similar to 50% distal pancreatectomy) to provide a hemi-pancreas for transplantation can develop diabetes mellitus or glucose intolerance [16, 17]. Kendall et al. [16] noted that 25% of healthy donors (7/28 donors) who provide a hemi-pancreas to a first-degree relative with type 1 diabetes mellitus develop impaired glucose tolerance within one year of the surgery. However, there was no obvious new-onset diabetes mellitus in these donors. A later study by Kumar et al. [17] evaluated the glucose metabolic state of 21 donors from 3 to 10 years after they had undergone hemi-pancreatectomy for organ donation. Of the 15 donors located on follow-up, 2 had been taking an antidiabetic agent, and the remaining 13 underwent metabolic evaluation. Abnormalities in glucose metabolism were identified in 7 of the 13 patients including 1 with diabetes and 6 with impaired glucose tolerance and/or impaired fasting glucose. While the rate of latent abnormalities was as high as 40% (6/15), the rate of overt diabetes mellitus development was 20% (3/15) during long-term follow-up. These results imply that the overt manifestation of diabetes after distal pancreatectomy 270

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with presumably normal pancreatic parenchyma is lower than previously considered. However, it still has a significant influence on glucose metabolism during long-term follow-up. For patients with chronic pancreatitis, the risk of diabetes mellitus shortly after distal pancreatectomy is 25– 50% [7, 10–12], and late-onset diabetes tends to be related to the clinical course of chronic pancreatitis [12]. For patients with normal pancreatic parenchyma and tumorous lesions, the rate of diabetes mellitus is relatively low shortly after distal pancreatectomy. However, the risk of developing impaired glucose tolerance and/or impaired fasting glucose in hemi-pancreatectomized donors is high. Hence, the development of late-onset diabetes mellitus should be monitored in these patients. Central Pancreatectomy Replication of beta cells is an important mechanism of beta-cell expansion in early childhood [18]. In obese or pregnant adult humans, the beta-cell mass is known to increase adaptively [19, 20]. However, in adulthood replication occurs to a considerably smaller extent, if at all. The capacity for beta-cell replication in humans is highMaeda /Hanazaki  

 

est immediately after birth and then becomes markedly lower through adulthood [18, 21]. A recent study of 13 patients with a median age of 51.9 years demonstrated that a 50% pancreatectomy does not promote beta-cell regeneration [21]. These findings explain the high incidence of impaired glucose metabolism after pancreatic resection and highlight the need for parenchyma sparing procedures. Central pancreatectomy, also called middle pancreatectomy, is the resection of the body segment of pancreatic parenchyma. Central pancreatectomy is utilized mostly for patients with small benign tumors located in the body of pancreas. While the proximal part of the remnant pancreas is usually left without anastomosis, the distal part of the remnant pancreas requires anastomosis to the gastrointestinal tract in order to drain the pancreatic juice into the alimentary tract. Adham et al. [22] reported that following central pancreatectomy for benign tumors, none of the 50 patients in their study developed diabetes mellitus during the median follow-up period of 55 months. Other studies also demonstrated excellent longterm preservation of endocrine function [23–25]. However, this complicated uncommon procedure is frequently associated with postoperative surgical complications [22–25]. The incidence of pancreatic fistula, which can be fatal, is 5–30% after distal pancreatectomy [10, 13, 14, 26, 27], and is theoretically higher after middle pancreatic resection since there are two possible sites of pancreatic fistula development. Pancreatic fistula may result in further destruction of islets cell mass due to inflammation itself and consequent stricture of the orifice of pancreatic duct to intestine, and the studies that compare the incidence of postoperative diabetes in those who develop pancreatic fistula and those who do not is required. Proximal Pancreatic Resection Proximal pancreatic resection is resection of the head of the pancreas. Duodenum-preserving pancreatic head resection avoids the resection of adjacent organs including duodenum, bile duct and gall bladder, which are commonly resected in pancreatoduodenectomy. Anastomosis of pancreatic duct of the remnant pancreas and gastrointestinal tract is necessary. Proximal pancreatic resection for chronic pancreatitis causes new-onset diabetes mellitus in 15–40% of patients [28–31]. A comparison of endocrine functions revealed that duodenum-preserving pancreatic head resection is superior to the usual pancreatoduodenectomy procedure partly because the intestinal hormones are spared and a smaller amount of pancreatic parenchyma is resected. Beger et al. [30] rePancreatogenic Diabetes

ported on their 26 years of experience performing duodenum-preserving head resection for the treatment of painful, complicated chronic pancreatitis. This surgical treatment provided pain relief to 91.3% of patients. Of the 504 patients in the study, 303 had undergone glucose metabolic assessment within a median follow-up period of 5.7 years. The investigation identified 134 patients with insulin-dependent diabetes mellitus (44%), 64 with newonset insulin-dependent diabetes mellitus (21%), 34 with improved metabolism, and 118 with normal oral glucose tolerance test results (39%). For patients with benign or malignant tumors, data on the incidence of diabetes mellitus after pancreatoduodenectomy are limited. Compared with chronic pancreatitis, fewer patients (18–27%) with presumably normal pancreatic parenchyma develop diabetes mellitus after pancreatic resection for benign pancreatic tumors [32, 33]. Amelioration of the diabetic state has been often observed after pancreatoduodenectomy for pancreatic cancer [34–37]. Mechanisms speculated to underlie the improved glucose metabolism following surgery include the removal of factors secreted by the adenocarcinoma and/ or inflammation due to obstructive lesions of the pancreas and delayed gastric emptying. Diabetogenic factors secreted by pancreatic tumors or local inflammation might alter glucose metabolism and cause insulin resistance; in this case, resection of the tumor can improve glucose metabolism [36, 37]. However, the diversity of measurement methods for insulin resistance has contributed to inconsistent findings among studies [36, 37]. Furthermore, improvement of the glycemic state commonly occurs after pancreatoduodenectomy and is rarely observed after distal pancreatectomy. Delayed gastric emptying or reduced caloric intake after pancreatoduodenectomy might improve postoperative glucose homeostasis because the velocity of gastric emptying is an important factor predicting the postprandial glucose level [36]. This hypothesis explains the improvement in metabolic state even after proximal pancreatic resection for chronic pancreatitis [11, 30]. However, delayed gastric emptying occurs in only about 20% of patients and resolves spontaneously a few weeks after pancreatectomy [32], and the relationship of delayed gastric emptying and occurrence of postoperative diabetes is not clearly revealed yet. Further studies of patients who undergo pancreatic resection for the treatment of benign or borderline tumorous lesions of the pancreatic head are required to elucidate the mechanisms underlying the impact of pancreatoduodenectomy on glucose homeostasis.

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271

Table 2. Pathophysiology of pancreatogenic diabetes

Acceleration of hypoglycemia Increased peripheral insulin sensitivity Malabsorption of dietary fat Reduced baseline glucagon Altered intestinal absorption Exocrine deficiency and abnormal intestinal function Acceleration of hyperglycemia Reduced hepatic sensitivity to insulin Deficiency of pancreatic polypeptide Reduced baseline insulin Increased glucagon sensitivity Reduced glucagon inhibition with hyperglycemia

Total Pancreatectomy Total pancreatectomy is performed for the multiple benign tumors requiring surgical intervention, refractory chronic pancreatitis and widely spreading tumor still having surgical implication [4, 6, 8]. This procedure is also performed in order to rescue the patient with severe pancreatic fistula or abdominal hemorrhage after pancreatic resection. After pancreatic resection, recurrent tumor within remnant pancreas occasionally requires surgical resection, resulting in total pancreatectomy at the end. Unlike other pancreatic resection procedure, total pancreatectomy causes 100% of pancreatic diabetes [4, 6, 8]. The lack of the pancreatic hormone leads to the extreme manifestation of the pancreatic diabetes.

Pathophysiology (table 2)

Insulin, which is secreted from beta cells distributed evenly throughout the pancreas [2], decreases the serum glucose concentration by suppressing hepatic gluconeogenesis and glycogenolysis and by facilitating hepatic glycogen synthesis [38]. Nondiabetic patients had lower fasting serum insulin and reduced C-peptide secretion after pancreatic resection [39, 40]. An increase in both peripheral sensitivity to insulin and the insulin-binding capacity of red blood cells are observed in pancreatogenic diabetes [41, 42]. The opposite effect is observed for insulin resistance in type 2 diabetes mellitus. The consequence of increased sensitivity to insulin is severe hypoglycemic attacks after excessive administration of insulin. While a reduction in insulin secretion is also observed in type 1 diabetes mellitus, insulin-binding 272

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capacity and sensitivity are usually unchanged. Thus, the amount of insulin receptors is not simply enhanced by up-regulation secondary to stimulant deficiency. A clear explanation at the molecular level has yet to be obtained, although intestinal malabsorption of fat in patients with pancreatic disease is thought to be responsible, as some studies show that adipocytes from rats fed a high fat diet bind less insulin than those from controls [41, 42]. Glucagon-secreting alpha cells are located predominantly in the body and tail of the pancreas [2]. During fasting in a healthy population, glucagon maintains adequate glucose production by hepatocytes through stimulation of glycogenolysis and gluconeogenesis that together function as counter-regulatory mechanisms to control hypoglycemia [38]. Like insulin, pancreatectomy reduces the fasting glucagon concentration, which might compensate for the decrease in insulin secretion and partly help to avoid the occurrence of pancreatogenic diabetes. By comparison, the decrease in glucagon from fasting promotes a hypoglycemic state when patients have been administered only a slight excess of insulin. Under physiological conditions, glucagon secretion decreases following a glucose load, thereby avoiding hyperglycemia [43, 44]. In type 2 diabetes, however, the suppression of glucagon induced by glucose is frequently decreased [44] and postprandial hyperglucagonemia is associated with hyperglycemia because of increased hepatic glucose production. Likewise, impaired glucose-induced glucagon suppression is observed in patients after pancreatic resection [45]. With the unsuppressed glucagon secretion, the increased hepatic sensitivity to glucagon [46] after pancreatic resection causes hyperglycemia in a state of insulin deficiency. Pancreatic polypeptide (PP), a 36-amino-acid polypeptide, is localized to specific cells called PP cells, which are located mostly in the ventral pancreatic head and uncinate process [47]. A study of patients with low levels of plasma PP following pancreatic resection [48] and chronic pancreatitis [49] demonstrated that hepatic glucose production during insulin infusion was not suppressed as it was in controls. PP administration to patients with PP deficiency was shown to improve their hepatic response to insulin. Thus, PP deficiency is related to hyperglycemia resulting from unsuppressed glucose production and is characteristic of pancreatogenic diabetes. These findings show the potential reversibility of PP deficiency in the abnormal glucose metabolism seen after pancreatic resection [48].

Maeda /Hanazaki  

 

Treatment

Despite the desire to avoid pancreatogenic diabetes after pancreatic resection, most cases require classical surgical resection, pancreatoduodenectomy, or distal pancreatectomy, for treatment of pancreatic tumors. When diabetes mellitus is mild, diet modification, exercise and/ or pharmacological treatment are appropriate. Total pancreatectomy results in insulin dependent pancreatogenic diabetes and the long-term outcomes of diabetic control have been studied [4, 6, 8, 50, 51]. Recently, Jethwa et al. [6] reported that the control of diabetes after total pancreatectomy is not necessarily associated with poor, relative to type 1 diabetes mellitus, glycemic control. In addition, the quality of life of patients after total pancreatectomy, performed to treat malignancy or chronic pancreatitis, is not always worse than previously considered [4]. However, hypoglycemia-related mortality and complications, such as nephropathy, neuropathy and retinopathy, should be taken into consideration [4–9]. Hypoglycemic attacks after exogenous insulin replacement are partly related to a deficiency in pancreatic enzymes. The keen observations of Linehan et al. [52] in 1988 from a series of total pancreatectomies revealed that the correct dose of pancreatic enzymes can produce optimal glycemic control and increase insulin demand, although these observations were not backed up by specific data. They proposed that rapid intestinal transit due to pancreatic insufficiency results in unpredictable glucose absorption and different levels of glucose uptake for every meal thus putting patients at risk of iatrogenic hypoglycemic attack. If this is true, then pancreatic enzyme supplementation is necessary not only to avoid exocrine insufficiency but also to achieve better glycemic control. In terms of parameters related to glycemic control, such as fasting glucose and HbA1c levels, the efficacy of pancreatic enzyme supplementation is controversial. However, one study demonstrated pancreatic supplementation to reduce the incidence of hypoglycemic attacks in patients with chronic pancreatitis and diabetes mellitus [53]. The usefulness of artificial endocrine pancreas in controlling blood glucose concentrations in hospitalized patients was recently demonstrated. This equipment continuously monitors blood glucose concentrations by withdrawing blood from a peripheral vein and administers insulin or glucose at rates determined to maintain the target glucose concentration. Artificial endocrine pancreas was shown to be safe and efficient in achieving tight perioperative blood glucose control without hypoPancreatogenic Diabetes

glycemic episodes even immediately after total pancreatectomy [54, 55]. Together with insulin replacement therapy, PP administration might alleviate the difficulties associated with controlling glucose levels. PP administration reportedly upregulates hepatic sensitivity to insulin and therefore might improve the clinical outcome of glycemic control [48, 49, 56]. However, the impact of glycemic control, in terms of preventing diabetes-related complications in the clinical setting, is not yet clear. Islet autotransplantation has been performed in certain institutes for the treatment of pancreatogenic diabetes mellitus following total pancreatectomy. Webb et al. [57] recently investigated the long-term outcomes of total pancreatectomy and simultaneous islet auto-transplantation in 46 patients mostly with chronic pancreatitis. Of these patients, 12 were insulin-independent for a median of 16.5 months. Employing the C-peptide assay this study also revealed that transplanted islets were functional in the long-term while the HbA1c level gradually increased after the operation. During follow-up, serum creatinine levels increased slightly, which was explained as an age-related increment in serum creatinine. They concluded that long-term insulin independence is not a usual outcome of islet auto-transplantation after total pancreatectomy. However, performance of this technique after total pancreatectomy achieves better glycemic control and can prevent diabetic complications. A limitation of this technique is that it can only be used to treat patients with benign diseases at qualified institutes. Microcapsuled islet transplantation might overcome the several problems entailed by the technique including immunosuppressant side effects if used [58, 59] and the possibility of spreading the malignant cells when autotransplantation is performed in patients with pancreatic adenocarcinoma. However, the efficacy of this procedure needs further improvement [59]. Another disadvantage of islet auto-transplantation seems to be associated morbidities such as portal thrombosis and splenic ischemia [60]. Although total pancreatectomy itself holds these surgical complications, differentiating the cause of complication is still difficult in part due to lack of adequate amount of cases. Therefore, prevention of these complications derived from different causes and treatment strategies remain an obstacle. We envision more patients benefiting from islet auto-transplantation as the technical difficulties associated with this treatment option are overcome [61].

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273

Conclusions

Pancreatogenic diabetes after pancreatic resection occurs because of a deficiency in pancreatic hormones and altered responses of related organs to lower hormone levels. Nutritional state and pancreatic exocrine function affect glycemic control. Recent data show the occurrence of new-onset diabetes mellitus after distal pancreatectomy for tumorous lesions to be relatively low. Nevertheless, a decreased fasting insulin level, impaired glucose tolerance, and impaired fasting glucose have been observed in many patients after distal pancreatectomy, placing these patients at risk of new-onset diabetes mellitus in the longterm. For this reason, parenchyma sparing surgery is recommended when this complicated surgical technique does not affect curability or increase the rate of complications. The treatment for pancreatogenic diabetes is diet modification, exercise, oral medication, and insulin replacement therapy. Glycemic control in patients with pancreatogenic diabetes following resection of majority

of parenchymal cells is difficult and hypoglycemic attacks are common because of increased peripheral sensitivity to insulin, decreased glucagon secretion, and irregular glucose absorption from the intestine. Critical damage and even death secondary to hypoglycemia remain as possible sequelae. In the clinical setting, the choice among surgical options should be made based on operative indications, motivation, the patient’s understanding and circumstances, and the risks of both pancreatogenic diabetes and pancreatic fistula. Total pancreatectomy and other aggressive surgical procedures, despite the destruction of exocrine and endocrine pancreatic functions, should remain the treatment of choice because patient care and postoperative quality of life following this procedure are improving. The development and improvement of new technologies such as islet auto-transplantation, PP replacement, and artificial endocrine pancreas will help to provide better glycemic control in patients requiring pancreatic resection.

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Erratum

In the article ‘Primers on Molecular Pathways – The NFAT Transcription Pathway in Pancreatic Cancer’ by König et al. [Pancreatology 2010;10:416–422; DOI: 10.1159/000315035], the Acknowledgements section is incomplete and should read: M.E.F.-Z. is supported by CA136526, Mayo Clinic Pancreatic SPORE P50 CA102701, CA125127, Mayo Clinic Cancer Center and Division of Oncology Research; V.E. is supported by Deutsche Forschungsgemeinschaft (TR 17 and KFO 210).

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