Effects of Pancreaticoduodenectomy on Glucose Metabolism

• Change of glucose metabolism after pancreaticoduodenectomy [ Time Frame: on the morning of surgery (day 1), 6 days later, and again at 1 and 6 months after surgery. ] [ Designated as safety issue: No ]
  response of 50 g oral glucose tolerance test, Measurement of glucagon-like peptide-1, Measurement of insulin, C-peptide, and glucagon concentrations
  
  

Questionaire All studied patients will be requested to self-complete a detailed questionnaire that collects information on demographic data, including usual adult height and weight, and history of DM in first-degree relatives. Existing medical conditions, including DM, duration of these medical problems, and current medications will also be inquired. The database will also include details of weight measured at the time of recruitment and body mass index (BMI), calculated as weight (kg)/height2 (m2). All studied patients will have FBG levels measured. Patients receiving prescription antidiabetic medications for previously diagnosed DM will be classified as having DM regardless of their FBG value. Among patients not reporting treatment for DM, classification of DM status will be based on the American Diabetes Association criteria16; patients will be classified as having DM if the FBG level is ≧126 mg/dL (7 mmol/L), as having impaired fasting glucose (IFG) if their FBG is between 100 and 125 mg/dL (5.6-6.9 mmol/L), and as having normal fasting glucose (NFG) if their FBG value is ≦99 mg/dL (5.5 mmol/L).

HOMA insulin resistance assessment (HOMA-IR)

Fasting blood samples will be drawn from all studied patients on the morning of surgery, 6 days later, and again at 1 and 6 months after surgery. Blood for glucose metabolism will be collected in tubes containing fluoride oxalate, and that for insulin estimation will be collected in tubes containing EDTA. These latter samples will be kept on ice until plasma is prepared, following which they will be stored at -70℃ until assayed in batches by radioimmunoassay. HOMA values will be calculated according to the following formula17:

HOMA=[glucose]mM x [insulin] pM / 22.5 x 6 50 g oral glucose tolerance test All studied patients will undergo a 2-h oral glucose tolerance test (OGTT) with 50 g glucose before surgery and at 1 and 6 months after operation. Patients' diabetes medication will be discontinued 3 days before OGTT. After insertion of an intravenous line, patients will receive 50 g glucose orally at 8:00 a.m. Blood samples will be collected in chilled EDTA tubes and centrifuged at 4℃ before storage at -70℃. Plasma concentrations of glucose, insulin, C-peptide, glucagon, glucose-dependent insulinotropic peptide (GIP), and active glucagon-like peptide 1 (GLP-1) will be measured at 0, 15, 30, 45, 60, 90, and 120 min during the 50 g glucose tolerance test.

Measurement of GLP-1 concentration Active GLP-1 concentration will be measured with an enzyme-linked immunosorbent assay (ELISA) kit (Linco Research Inc.) The intr-assay and inter-assay coefficient of variations (CVs) will be 7.4% and 8%, respectively. The assay is 100% specific for GLP-1 (7-36) and GLP-1(7-37), and does not react with other forms GLP-1 (1-36 amide, 1-37, 9-36 amide, or 9-37).

Measurement of GIP concentration Total GIP concentrations will be measured with an ELISA kit (Linco Research Inc.). The assay is 100% specific for GIP 1-42 and GIP 3-42, and does not cross react with GLP-1, GLP-2, oxyntomodulin, or glucagon. The intra-assay and inter-assay CVs will be 3.0-8.8% and 1.8-6.1%, respectively.

Measurement of insulin, C-peptide, and glucagon concentrations Insulin and C-peptide will be measured by chemiluminescence immunoassay (Roche E170, Roche Diagnostics, Indianapolis, IN, USA). Glucagon concentrations will be measured by radioimmunoassay (Siemens Medical Solution Diagnostics, Los Angels, CA, USA).

Statistics All data will be analyzed using SPSS Version 11.0 for Windows (SPSS Inc., Chicago, IL, USA). Data will be presented as means ± SD unless otherwise stated. Area under the curve (AUC) values will be calculated using the trapezoidal rule. Comparisons before and after PD surgery will be made using the Wilcoxon signed rank-sum test. P -values<0.05 will be considered significant.