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OBSERVATIONS Islet Autotransplantation Restores Normal Glucose Tolerance in a Patient With Chronic Pancreatitis
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mpaired glucose tolerance is a frequent complication of chronic pancreatitis (CP) that over time leads to diabetes (1). Intractable abdominal pain from CP that can no longer be managed by oral pancreatic enzymes and by narcotic analgesics is treated by surgery. To avoid diabetes onset following pancreatectomy, combined islet autotransplantation has been offered to the patients who suffered from CP in Leicester, U.K., since 1994 (2,3) (http://hpb.org.uk/hpbunitspecial ist.php?page_id⫽11). Here, we present a case report of a patient that suffered from CP and had an abnormal oral glucose tolerance test (OGTT) before pancreatectomy (showing diabetes and impaired glucose tolerance) but since surgery has had normal results. Indeed, OGTT results of stimulated blood glucose were 11.9 and 8 mmol/l at 19 and 11 months presurgery, respectively. At the time of the surgery, the patient was a 43-year-old woman. The etiology of CP was idiopathic, and the patient suffered from chronic epigastric pain for more than 2 years before surgery. On 28 May 2002, the patient underwent a total pancreatectomy combined with islet autotransplantation during an 8-h operation (including the islet preparation process, as previously described [2,3]). The weight of the pancreas was 55 g, and after
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digestion, 14 ml pancreatic tissue (tissuepacked volume) was obtained. A total of 232,721 islets, corresponding to 57,296 islet equivalents (IEQ), 18% free of acinar tissue, was infused into the left branch of the portal vein. The patient remains insulin independent 5 years after autoislet transplantation with 954.93 IEQ/kg body wt. Intravenous insulin was stopped 8 days postoperatively; her blood glucose levels were monitored every 4 h and remained stable throughout her hospital stay (21 days). She did not experience any perioperative complications. By 2 years postoperation, she began to experience regular postprandial hypoglycemic episodes, which is a well-known prolonged insulin response of transplanted islets due to a defective glucagon secretion (4,5). Annual follow-up visits revealed normal OGTT results. Her fasting Cpeptide levels have remained detectable, and the C-peptide production in response to an oral glucose load is significantly higher than basal levels (1.44 and 5.02 ng/ml, respectively, at 5 years postsurgery). To our knowledge, this is the first case report of a CP patient, with abnormal OGTT before surgery, who has become insulin independent after autoislet transplantation with less than 1,000 IEQ/kg body wt. These results show that it is possible to restore normal glucose tolerance with total pancreatectomy combined with islet autotransplantation in CP patients with borderline diabetes. Furthermore, these results support the concept that insulin independence can be achieved in patients with islet cell autograft of a low number of islets. Indeed, from our series, no correlation was found between the islet number and the outcome of the islet transplant in terms of insulin independence (2). SEVERINE ILLOUZ, PHD1 M’BALU WEBB, MSC1
CRISTINA POLLARD, BA1 PATRICK MUSTO, FCA(SA)2 KIERAN O’REILLY, MBCHB3 DAVID BERRY, MD1 ASHLEY DENNISON, MD1 From the 1Department of Hepatobiliary and Pancreatic Surgery, University Hospital of Leicester, Leicester, U.K.; the 2Department of Anesthesiology, University Hospital of Leicester, Leicester, U.K.; and the 3Department of Pathology, University Hospital of Leicester, Leicester, U.K. Address correspondence to Dr. Severine Illouz, PhD, Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, U.K. E-mail:
[email protected]. DOI: 10.2337/dc07-1075 © 2007 by the American Diabetes Association.
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References 1. Banks PA: Epidemiology, natural history, and predictors of disease outcome in acute and chronic pancreatitis. Gastrointest Endosc 56 (Suppl. 6):S226 –S230, 2002 2. Clayton HA, Davies JE, Pollard CA, White SA, Musto PP, Dennison AR: Pancreatectomy with islet autotransplantation for the treatment of severe chronic pancreatitis: the first 40 patients at the Leicester General Hospital. Transplantation 76:92– 98, 2003 3. White SA, Davies JE, Pollard C, Swift SM, Clayton HA, Sutton CD, Wemyss-Holden S, Musto PP, Berry DP, Dennison AR: Pancreas resection and islet autotransplantation for end-stage chronic pancreatitis. Ann Surg 233:423– 431, 2001 4. Kendall DM, Teuscher AU, Robertson RP: Defective glucagon secretion during sustained hypoglycemia following successful islet allo- and autotransplantation in humans. Diabetes 46:23–27, 1997 5. Paty BW, Ryan EA, Shapiro AM, Lakey JR, Robertson RP: Intrahepatic islet transplantation in type 1 patients does not restore hypoglycemic hormonal counterregulation or symptom recognition after insulin independence. Diabetes 51:3428 – 3434, 2002
DIABETES CARE, VOLUME 30, NUMBER 12, DECEMBER 2007
