c-peptide and Pancreatitis--Chronic

We aimed to investigate how assimilation of nutrients affects the postprandial responses of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and to evaluate the effect of pancreatic enzyme substitution (PES) on insulin secretion in patients with chronic pancreatitis (CP) and pancreatic exocrine insufficiency (PEI). Eight male patients with CP and PEI were studied. Blood was sampled frequently on two separate days after ingestion of a liquid meal with and without PES, respectively. Eight healthy male subjects served as a control group. beta-Cell responsiveness was estimated as changes in insulin secretion rates in response to changes in postprandial plasma glucose (PG). There was no difference in the PG incremental area under curve (AUC) for patients with and without PES [406 +/- 100 vs. 425 +/- 80 mM.4 h (mean +/- SE), P = 0.8]. The response of total GLP-1 was higher after PES (AUC: 7.8 +/- 1.2 vs. 5.3 +/- 0.6 nM.4 h, P = 0.01), as was the response of total GIP (AUC: 32.7 +/- 7.5 vs. 21.1 +/- 8.3 nM.4 h, P = 0.01). Concurrently, both plasma insulin, plasma C-peptide, and total insulin secretion increased after PES (AUC: 17.7 +/- 4.2 vs. 13.6 +/- 2.9 nM.4 h, P = 0.02; 237 +/- 31.4 vs. 200 +/- 27.4 nM.4 h, P = 0.005; and 595 +/- 82 vs. 497 +/- 80 pmol.kg(-1).4 h, P = 0.01, respectively). beta-Cell responsiveness to glucose was not significantly different on the two study days for patients with CP. These results suggest that the secretion of GLP-1 and GIP is under influence of the digestion and absorption of nutrients in the small intestine and that PES increases insulin secretion.

Topics: Aged; Amylases; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Lipase; Male; Middle Aged; Pancreas; Pancreatitis, Chronic; Peptide Hydrolases; Postprandial Period; Steatorrhea; Triglycerides

More than one-third of chronic pancreatitis patients will eventually develop diabetes, recently classified as post-chronic pancreatitis diabetes mellitus (PPDM-C). This study was aimed to investigate the pancreatic and gut hormone responses to a mixed meal test in PPDM-C patients, compared with non-diabetic chronic pancreatitis (CP), and type 2 diabetes patients or healthy controls.. Sixteen patients with PPDM-C, 12 with non-diabetic CP as well as 10 with type 2 diabetes and healthy controls were recruited. All participants underwent mixed meal tests, and blood samples were collected for measurements of blood glucose, C-peptide, insulin, glucagon, pancreatic polypeptide (PP), ghrelin, peptide YY, glucagon like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP). Indices of insulin sensitivity and secretion were calculated. Repeated measures analysis of variance was performed.. Participants with PPDM-C exhibited decreases in both fasting and postprandial responses of C-peptide (P < 0.001), insulin (P < 0.001), ghrelin (P < 0.001) and PYY (P = 0.006) compared to participants with type 2 diabetes and healthy controls. Patients with CP showed blunted glucagon, PP and incretin reactions, while the responses were increased in patients with PPDM-C compared to controls. The level of insulin sensitivity was higher for PPDM-C than type 2 diabetes (P < 0.01), however the indices for early/late-phase and overall insulin secretion (P < 0.01) were lower.. Patients with PPDM-C are characterized by decreased C-peptide, insulin, ghrelin and PYY responses, and similar levels of glucagon, PP, GIP and GLP-1 compared to those with type 2 diabetes. The above findings, when confirmed in a larger population, may prove helpful to establish the diagnosis of PPDM-C, and should promote study on underlying pathophysiological mechanisms.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Pancreatitis, Chronic; Peptide YY

Studies evaluating endocrine and exocrine functions in fibrocalculous pancreatic diabetes (FCPD) are scarce.. Insulin, C-peptide, glucagon, incretin hormones (glucagon-like peptide 1 [GLP-1] and gastric inhibitory peptide [GIP]), and dipeptidyl peptidase IV (DPP-IV) were estimated in patients with FCPD (n = 20), type 2 diabetes mellitus (T2DM) (n = 20), and controls (n = 20) in fasting and 60 minutes after 75 g glucose.. Fasting and post-glucose C-peptide and insulin in FCPD were lower than that of T2DM and controls. Plasma glucagon decreased after glucose load in controls (3.72, 2.29), but increased in T2DM (4.01, 5.73), and remained unchanged in FCPD (3.44, 3.44). Active GLP-1 (pmol/L) after glucose load increased in FCPD (6.14 to 9.72, P = <.001), in T2DM (2.87 to 4.62, P < .001), and in controls (3.91 to 6.13, P < .001). Median active GLP-1 in FCPD, both in fasting and post-glucose state (6.14, 9.72), was twice that of T2DM (2.87, 4.62) and 1.5 times that of controls (3.91, 6.13) (P < .001 for all). Post-glucose GIP (pmol/L) increased in all: FCPD (15.83 to 94.14), T2DM (21.85 to 88.29), and control (13.00 to 74.65) (P < .001 for all). GIP was not different between groups. DPP-IV concentration (ng/mL) increased in controls (1578.54, 3012.00) and FCPD (1609.95, 1995.42), but not in T2DM (1204.50, 1939.50) (P = .131). DPP-IV between the three groups was not different. Fecal elastase was low in FCPD compared with T2DM controls.. In FCPD, basal C-peptide and glucagon are low, and glucagon does not increase after glucose load. GLP-1, but not GIP, in FCPD increases 1.5 to 2 times as compared with T2DM and controls (fasting and post glucose) without differences in DPP-IV.. 背景: 评价纤维结石性胰腺糖尿病(FCPD)内分泌和外分泌功能的研究很少。 方法: 测定FCPD组(n=20)、2型糖尿病(T2 DM)组(n=20)和对照组(n=20)空腹和75g葡萄糖后60min的胰岛素、C肽、胰高血糖素、肠泌素(胰高血糖素样肽1[GLP-1]和胃抑制肽[GIP])、二肽基肽酶IV(DPP-IV)水平。 结果: FCPD组空腹和糖负荷后C肽、胰岛素水平均低于T2 DM组和对照组。对照组糖负荷后胰高血糖素(pmol/L)降低(3.72; 2.29); T2 DM组升高(4.01; 5.73); FCPD组(3.44; 3.44)无明显变化。FCPD组(6.14~9.72; P=<0.001)、T2 DM组(2.87~4.62; P<0.001)和对照组(3.91~6.13; P<0.001)糖负荷后活性GLP-1(pmol/L)升高。FCPD组空腹和糖负荷后GLP-1(pmol/L)活性中位数(6.14; 9.72)是T2 DM组(2.87; 4.62)的两倍; 是对照组(3.91; 6.13)的1.5倍(P<0.001)。糖负荷后GIP(pmol/L)在所有组别中都升高:FCPD(15.83~94.14)、T2DM(21.85~88.29)、对照组(13.00~74.65), P<0.01。不同组间GIP差异无统计学意义。对照组(1578.54,3012.00)和FCPD组(1609.95,1995.42)的DPP-IV浓度(ng/mL)升高; 而T2 DM组(1204.50,1939.50)的DPP-IV浓度无明显变化(P=0.131)。DPP-IV于三组间差异无统计学意义。FCPD组中粪弹性蛋白酶低于T2 DM组对照组。 结论: FCPD患者糖负荷后基础C肽和胰高血糖素降低; 在糖负荷后胰高血糖素不升高。FCPD的GLP-1; 而不是GIP; 与T2 DM和对照组(空腹和糖负荷后)相比升高了1.5-2倍; 而DPP-IV没有差异.

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; C-Peptide; Calcinosis; Case-Control Studies; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Female; Fibrosis; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Incretins; Insulin; Male; Middle Aged; Pancreatitis, Chronic; Time Factors; Young Adult

To study the incidence of glucose intolerance in CP patients without diabetes by performing oral glucose tolerance test (OGTT).. We screened consecutive Indian CP patients without diabetes over 6 months by performing OGTT and correlated with physical characteristics and glycated hemoglobin (HbA1c). We also compared c-peptide and pancreatic polypeptide response in different groups based on OGTT. Relevant statistical tests were performed. P < 0.05 was considered significant.. Total of 171 patients were screened. Mean duration of CP was 5.03 ± 4.32 years. 55 were detected to have prediabetes and 40 DM on OGTT. CP patients with diabetes and prediabetes had significantly dilated pancreatic duct compared to non-diabetic CP (4.2 ± 2.7 mm, 3.6 ± 2.7 mm, 2.84 ± 2.25 mm; p = 0.018). Fasting blood glucose (FBS) and 2-hour OGTT were 109.35 ± 19.06, 97.47 ± 11.94, 85.24 ± 9.95 and 236.13 ± 31.42, 154.65 ± 19.53, 112.89 ± 16.32 in patients with DM, prediabetes and CP patients without diabetes (p < 0.0001). There was a good c-peptide response (p = 0.001) and reduced pancreatic polypeptide response (p = 0.003) in CP patients compared to controls.. Early in the course of disease reduced pancreatic polypeptide response in the presence of good c-peptide response may result in development of DM.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Intolerance; Humans; Male; Pancreatitis, Chronic

The combined use of interleukin-1β and tumor necrosis factor-α blockers in the peritransplant period has improved outcomes of total pancreatectomy with islet autotransplantation (TPIAT). However, these drugs may suppress the immune system, resulting in severe infection.. We retrospectively investigated the impact of microbial-contaminated islet product on posttransplant complications and metabolic outcomes of TPIAT patients receiving the IL-1β and TNF-blockade treatment at our center.. Among 108 TPIAT patients, 37 patients (34%) received contaminated products. Preoperative stent treatment and fibrosis score were independent risk factors for the contamination. There were no significant differences between the contaminated and noncontaminated product groups in posttransplant infectious complication rate, length of hospitalization, or readmission rate. However, islet equivalents (P < .0001) and insulin independence rate (P = .036) at 6 months were significantly lower for patients receiving contaminated product.. These results suggest that combined anti-inflammatory drug use is safe and well tolerated in TPIAT patients who receive contaminated islet product and does not increase the rate of infectious complications; however, contaminated islet product is associated with poor metabolic outcomes.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Bacterial Infections; C-Peptide; Etanercept; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Middle Aged; Pancreatectomy; Pancreatitis, Chronic; Retrospective Studies; Risk Factors; Transplantation, Autologous; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

Little data exist describing the change over time in islet function and glycemic control in patients with chronic pancreatitis (CP).. In 325 CP patients who underwent 2 mixed meal tolerance tests and/or glycated hemoglobin (HbA1c) levels, we estimated the rate of change in metabolic measures per 6 months and assessed the association between potential risk factors for diabetes and rate of change using multivariate regression models.. Per 6-month time, HbA1c increased by 0.062% with a standard error of 0.029% (P = 0.037) and the ratio (area under the curve (AUC) C-peptide to AUC glucose from mixed meal tolerance testing) decreased by 0.0028 with a standard error of 0.0011 (P = 0.014). We observed more rapid decline in smokers (AUC C-peptide, P = 0.043) and patients with surgical drainage (AUC glucose, P = 0.001; ratio, P = 0.03) or with calcific pancreatitis (HbA1c, P = 0.003). In multivariate models, AUC C-peptide and ratio declined at a greater rate in smokers and HbA1c in those with pancreatic calcifications (both P < 0.05).. We observed a measurable decline in β-cell function and glycemic control in patients with CP. Patients with a history of tobacco smoking, surgical drainage, or pancreatic calcification may be at highest risk.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Disease Progression; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Middle Aged; Pancreatic Diseases; Pancreatitis, Chronic; Risk Factors; Young Adult

Diabetes frequently develops in patients with chronic pancreatitis. We examined the alterations in the glucagon response to hypoglycemia and to oral glucose administration in patients with diabetes due to chronic pancreatitis.. Ten patients with diabetes secondary to chronic pancreatitis were compared with 13 patients with type 2 diabetes and 10 healthy control subjects. A stepwise hypoglycemic clamp and an oral glucose tolerance test (OGTT) were performed.. Glucose levels during the OGTT were higher in patients with diabetes and chronic pancreatitis and lower in control subjects (. α-Cell responses to oral glucose ingestion and to hypoglycemia are disturbed in patients with diabetes and chronic pancreatitis and in patients with type 2 diabetes. The similarities between these defects suggest a common etiology.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose Tolerance Test; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Pancreatitis, Chronic

Total pancreatectomy with islet autotransplantation is increasingly being performed remotely, that is, removing the pancreas in 1 location, isolating the islet cells in another location, then returning the islets to the original location for reimplantation into the patient. We determined the influence of extended cold ischemia time on key clinical outcomes in remote islet autotransplantation.. We evaluated patients who underwent remote islet autotransplantation at 2 centers from 2011 to 2014. Patients were divided into 2 groups: those with and those without a decrease in C-peptide greater than 50% from baseline. The primary clinical outcome was the quantity of isolated islet equivalents per kilogram body weight (IEQs/kg).. Twenty-five patients met inclusion criteria; 15 had a decrease in C-peptide greater than 50% from baseline and had lower corresponding IEQs/kg compared with those without a decrease greater than 50% (4045 vs 6654 IEQs/kg, P = 0.01). There was no difference in cold ischemia time between the 2 groups (664 vs 600 minutes, P = 0.25). Daily insulin use at 1 year nearly met statistical significance (25.3 vs 8 U, P = 0.06), as did glycated hemoglobin (8.07 vs 6.69 mmol/L, P = 0.06).. Cold ischemia time does not influence islet yield in patients undergoing pancreatectomy with remote isolation.

Topics: Acute Disease; Adult; C-Peptide; Cold Ischemia; Female; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Linear Models; Male; Middle Aged; Pancreatectomy; Pancreatitis; Pancreatitis, Chronic; Retrospective Studies; Time Factors; Transplantation, Autologous; Treatment Outcome

Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation.. We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant.. Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group.. At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.

Topics: Acute Disease; Adult; C-Peptide; Cohort Studies; Diabetes Mellitus; Female; Glycated Hemoglobin; Health Facilities; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans Transplantation; Male; Pancreatectomy; Pancreatitis; Pancreatitis, Chronic; Postoperative Complications; Recurrence; Retrospective Studies; Transplantation, Autologous; Treatment Outcome

Diabetes mellitus is a frequent consequence of chronic pancreatitis (CP). Little is known about pancreatic endocrine function before the development of diabetes mellitus in CP, particularly in females, or those without calcific and/or alcoholic pancreatitis.. Twenty-five nondiabetic adult patients with CP (19 female; mean [SE] age, 34.2 [2.4] years) were compared with 25 healthy controls matched for age, sex, and body mass index. Subjects underwent frequent sample intravenous glucose tolerance testing (FSIVGTT) and mixed meal tolerance testing (MMTT).. Mean (SE) fasting glucose was higher in patients with CP (89.5 [2.3] mg/dL) than in controls (84.4 [1.2] mg/dL, P = 0.04). On MMTT, patients with CP had a higher area under the curve (AUC) glucose and AUC glucagon compared with controls (P ≤ 0.01). The AUC C-peptide was equivalent (P = 0.6) but stimulated C-peptide at 30 minutes was lower in patients with CP (P = 0.04). Mean insulin sensitivity index calculated from the FSIVGTT was lower in CP group, indicating reduced insulin sensitivity (P ≤ 0.01). Disposition index (insulin secretion adjusted for insulin sensitivity on FSIVGTT) was lower in patients with CP (P = 0.01).. Patients with CP had higher fasting and MMTT glucose levels, without a compensatory increase in insulin secretion suggesting subtle early islet dysfunction. Our cohort had relative hyperglucagonemia and was less insulin sensitive than controls.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Disease Progression; Fasting; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreatitis, Chronic

Because several studies for autoimmune pancreatitis (AIP) have revealed pancreatic calcification resembling that in chronic pancreatitis (CP), we sought to clarify whether AIP could transform into chronic features similar to advanced CP with severe pancreatic dysfunction.. Pancreatic functions of 92 AIP patients, 47 definite CP patients, and 30 healthy controls were assessed by fecal elastase-1 concentration (FEC), fasting immunoreactive insulin (IRI), and homeostatic model assessment (HOMA)-R.. The 92 AIP patients included 17 (18%) with severe calcification (SC) and 75 without. The FEC levels in AIP and CP patients were significantly lower than that in controls. Exocrine insufficiency defined as FEC less than 200 μg/g was 39% in AIP without SC, 56% in AIP with SC, and 74% in CP. Fasting IRI and C-peptide reactivity values in CP were significantly lower than those in AIP, with no significant differences between AIP subgroups. The prevalence of endocrine insufficiency according to fasting IRI less than 5.0 μU/mL was 26% in AIP without SC, 31% in AIP with SC, and 59% in CP, respectively. HOMA-R values were significantly higher in all AIP groups than in CP.. Autoimmune pancreatitis can transform into a state of pancreatic insufficiency after calcification that is less severe than that in definite CP.

Topics: Autoimmune Diseases; C-Peptide; Calcinosis; Humans; Pancreas; Pancreatitis; Pancreatitis, Chronic

Islet autotransplant (IAT) may ameliorate postsurgical diabetes following total pancreatectomy (TP), but outcomes are dependent upon islet mass, which is unknown prior to pancreatectomy. We evaluated whether preoperative metabolic testing could predict islet isolation outcomes and thus improve assessment of TPIAT candidates. We examined the relationship between measures from frequent sample IV glucose tolerance tests (FSIVGTT) and mixed meal tolerance tests (MMTT) and islet mass in 60 adult patients, with multivariate logistic regression modeling to identify predictors of islet mass ≥2500 IEQ/kg. The acute C-peptide response to glucose (ACRglu) and disposition index from FSIVGTT correlated modestly with the islet equivalents per kilogram body weight (IEQ/kg). Fasting and MMTT glucose levels and HbA1c correlated inversely with IEQ/kg (r values -0.33 to -0.40, p ≤ 0.05). In multivariate logistic regression modeling, normal fasting glucose (<100 mg/dL) and stimulated C-peptide on MMTT ≥4 ng/mL were associated with greater odds of receiving an islet mass ≥2500 IEQ/kg (OR 0.93 for fasting glucose, CI 0.87-1.0; OR 7.9 for C-peptide, CI 1.75-35.6). In conclusion, parameters obtained from FSIVGTT correlate modestly with islet isolation outcomes. Stimulated C-peptide ≥4 ng/mL on MMTT conveyed eight times the odds of receiving ≥2500 IEQ/kg, a threshold associated with reasonable metabolic control postoperatively.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Pancreatectomy; Pancreatitis, Chronic; Postoperative Complications; Preoperative Care; Prognosis; Prospective Studies; Risk Factors; Transplantation, Autologous

In the article results of supervision of the patients with chronic pancreatitis and dysfunction of Oddi's sphincter, pancreatic type, in polyclinic were presented. Among them: 50 children received in clinic therapeutic complex offered by us which included: phytoenzyme, spasmolytic and antioxidant. 50 children were treated in traditional way. Screening of functional condition of the pancreas revealed decreasing percentage of moderate exocrine insufficiency of pancreas (10% of incidences) in children with recurrent course of pancreatitis. In long-lasting course of pancreatitis in this group percentage of patients with moderate exocrine insufficiency was decreased due to 15%. At the same time, in patients with moderate and severe exocrine insufficiency (55 and 20% subsequently) which improves non complete efficiency of basic therapy.

Topics: Adolescent; C-Peptide; Child; Feces; Female; Follow-Up Studies; Gastrointestinal Agents; Humans; Male; Pancreas; Pancreatic Elastase; Pancreatitis, Chronic; Peptide Hydrolases; Quercetin; Severity of Illness Index; Sphincter of Oddi; Treatment Outcome; Trimebutine

The relationship between magnetic resonance imaging (MRI), histopathology, and islet yield was examined for chronic pancreatitis patients undergoing total pancreatectomy and autologous islet cell transplant (TP-AIT) to determine if the yield can be predicted by pre-operative MRI.. MRI sequences and histopathology were scored and compared for patients from whom ≤2,500 islet equivalents/kg were obtained with those from whom >2,500 islet equivalents/kg were obtained.. Twenty patients, 14 female, mean age 40.20 ± 12.5 years, (range 19-63) underwent MRI before TP-AIT; mean 3,724 ± 891 islet equivalents/kg body weight, median 2,970, (range 76-17,770) were procured. There was no correlation between islet cell numbers and pancreas weight, HgbA1c, or c-peptide. The most common MRI sequence abnormality was the delayed interstitial phase, 14/18 (78 %). The other common MRI sequence abnormalities were, precontrast T1W 3D GRE sequence, 13/19 (68 %), and the arterial perfusion phase, 11/18 (61 %). The pancreatic duct was dilated in 10/20 (50 %). Parenchymal atrophy was noted in 10/20 (50 %). Median scores for individual MRI sequences were greater in patients with an islet cell yield of ≤2,500 islet equivalents/kg; for the delayed interstitial phase the difference was significant (median 2.5, range 1-3 versus median 0.5, range 0-3, P = 0.034). Histologically the most common feature was fibrosis, (17/17, 100 %); the score for fibrosis was greater for patients with an islet cell yield of ≤2,500 islet equivalents/kg (median 6.0, range 5-7 versus median 4.0, range 3-7, P = 0.024).. A diminished islet yield may be predicted on the basis of the delayed interstitial phase MRI sequence.

Topics: Adult; C-Peptide; Female; Glycated Hemoglobin; Humans; Islets of Langerhans Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Organ Size; Pancreas; Pancreatectomy; Pancreatitis, Chronic; Transplantation, Autologous; Young Adult

Islet autotransplantation (IAT) is performed in nondiabetic patients with chronic pancreatitis at the time of total pancreatectomy (TP) to minimize risk of postoperative diabetes. The role of TP-IAT in patients with chronic pancreatitis and C-peptide-positive diabetes is not established. We postulate that IAT can preserve beta cell mass and thereby benefit patients with preexisting diabetes undergoing TP.. Preoperative metabolic testing, islet isolation outcomes, and subsequent islet graft function were reviewed for 27 patients with diabetes mellitus and chronic pancreatitis undergoing TP-IAT. The relationships between the results of preoperative metabolic testing and islet isolation outcomes were explored using regression analysis.. Mean islet yield was 2060 (SD, 2408) islet equivalents/kg. Peak C-peptide (from mixed meal tolerance testing) was the strongest predictor of islet yield, with higher stimulated C-peptide levels associated with greater islet mass. Half of the patients who had C-peptide levels measured after transplantation demonstrated C-peptide production at a level that conveys protective benefit in type 1 diabetes (≥ 0.6 ng/mL).. These findings provide proof of concept that significant islet mass can be isolated in patients with chronic pancreatitis and C-peptide-positive diabetes mellitus undergoing TP-IAT. Stimulated C-peptide may be a useful marker of islet mass before transplantation in these patients.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Glucose; C-Peptide; Chi-Square Distribution; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin-Secreting Cells; Islets of Langerhans Transplantation; Male; Middle Aged; Pancreatectomy; Pancreatitis, Chronic; Transplantation, Autologous; Treatment Outcome; Young Adult

To reveal the specific features of pancreatogenic diabetes mellitus (DM) and to discuss the principles of its medical therapy.. Sixty-six patients (55 men and 11 women) aged 30 to 65 years with chronic pancreatitis (CP) were examined. The disease was accompanied with pancreatic calcification and cyst formation in 22 and 13 patients, respectively; 5 patients were found to have a pseudotumorous form of CP and 10 had clinically and laboratorily verified DM. 14 resections and 11 drainages for complicated CP were performed. Its diagnosis was established on the basis of clinical, instrumental, and laboratory findings. Pancreatic exocrine function was evaluated from the results of the 13C-trioctanain breath test (BT) that is designed for its in vivo diagnosis. The level of C-peptide was studied by an enzyme immunoassay.. The findings suggest that pancreatic exocrine function is diminished in CP patients both with and without complications as compared with the normal value in 44% (24.3 +/- 1.7 and 26.6 +/- 1.3%, respectively), as shown by BT. According to the results of BT, a substantial decrease in the total proportion of a released label was noted in patients with CP and pancreatic calcification, diabetes mellitus, after resection operations for complications of CP and there were also significant differences, as compared to a group of CP patients without complications. In these patient groups, the level of C-peptide fell to a larger extent than that in CP patients without complications and in patients with CP and DM it was decreased to 0.11 +/- 0.02 ng/ml, the normal level being 0.7-1.9 ng/ml. There was a direct correlation between C-peptide levels and BT results in the patients with CP after resection operations. Insulin antibodies were absent in all the examined patients with CP, which proves the specific type of DM in CP. These are detectable only in type 1 DM. Seven patients with CP and DM were found to have calcification, 5 underwent resection operations, 3 had calcification and underwent pancreatic resection operations.. The development of DM may be predicted in CP patients with formation of pancreatic calcification and resections. In these patients, pancreatic exocrine dysfunction achieves a severe degree.

Topics: Adult; Breath Tests; C-Peptide; Calcinosis; Diabetes Mellitus; Female; Glucose; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Pancreatectomy; Pancreatitis, Chronic

Glucose homeostasis is significantly altered immediately after partial pancreatectomy. The present study examined the long-term consequences of a hemipancreatectomy in 10 patients with chronic pancreatitis and 10 patients with benign pancreatic and extrapancreatic tumors. A 240-minute oral glucose challenge was performed before and shortly after pancreatic surgery, as well as after a follow-up of 3.1 ± 0.5 years. Plasma concentrations of glucose, insulin, and C-peptide were determined; and indices of insulin sensitivity and insulin secretion were calculated. In both groups of patients, fasting and postchallenge glucose concentrations were significantly altered immediately after surgery, but returned to preoperative levels at the time of follow-up (P < .0001). Postchallenge insulin and C-peptide concentrations were reduced immediately after surgery (P < .0001), but were partly normalized at the time of follow-up (P < .0001). These changes were not accompanied by improvements in insulin sensitivity (Matsuda index). However, the oral disposition index revealed a significant recovery of β-cell function at the time of follow-up (P < .05). These findings demonstrate a capacity for recovery of glucose control after partial pancreatectomy and suggest that β-cell function can improve significantly over time even in adult humans.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis, Chronic; Recovery of Function

Total or partial pancreatectomy followed by autologous islet transplantation is a therapeutic option for the treatment of refractory chronic pancreatitis (CP). Maximization of islet yields from fibrotic and inflamed organs is crucial for prevention of posttransplant diabetes. We adapted technical advancements developed for islet allotransplantation toward islet autotransplantation. Eight patients (two men, six women; ages 24-58 years) underwent total (n = 7) or partial (n = 1) pancreatectomy for the treatment of CP refractory to maximal medical management. Pancreata were preserved in UW solution (UW group) in initial three cases and the last five pancreata were preserved with pancreatic ductal injection followed by ET-Kyoto/oxygenated PFC solutions (DI+TLM group). Islets were isolated by modified Ricordi method and were purified only in one case. All islet infusions were performed under general anesthesia via direct vein injection into the portal venous system with pressure monitoring. Total islet yields (129,314 ± 51,627 vs. 572,841 ± 116,934 IEQ, p < 0.04), islet yield/pancreas weight (1,233 ± 359 vs. 6,848 ± 847 IEQ/g, p < 0.003), and islet yield/patient body weight (1,951 ± 762 vs. 7,305 ± 1,531 IEQ/kg, p < 0.05) were significantly higher in the DI+TLM group when compared to the UW group. Pellet size was also higher (5.3 ± 0.3 vs. 13.5 ± 3.4 ml) in the DI+TLM group, suggesting that this method of preservation effectively protected pancreatic tissue against autolysis. First month posttransplant basal C-peptide and the secretory unit of islet transplant objects (SUITO) index were also higher in the DI+TLM group when compared to the UW group (2.0 ± 0.3 vs. 1.4 ± 0.4 ng/ml and 42.6 ± 12.7 vs. 14.6 ± 5.6, respectively). There were no technical complications related to the infusion. Our results suggest that higher islet yields can be achieved even from chronically inflamed and fibrotic organs using DI+TLM. The techniques applied for islet isolations from normal pancreata are showing promise for fibrotic pancreata from CP patients.

Topics: Adenosine; Adult; Allopurinol; Body Weight; C-Peptide; Epoprostenol; Female; Fluorocarbons; Follow-Up Studies; Glutamine; Glutathione; Humans; Hydroxyethyl Starch Derivatives; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Magnesium Sulfate; Male; Middle Aged; Niacinamide; Organ Preservation; Organ Preservation Solutions; Pancreatitis, Chronic; Raffinose; Transplantation, Autologous; Trehalose

In order to identify features of the course pancreatic diabetes and discussion of the principles of conservative therapy were examined 66 patients with CP in age of 30 to 65 years (55 men, 11 women). Among them in 22 cases disease was followed with formation of calcification of pancreas, 13 - pancreatic cysts, and 5 revealed pseudo tumor form of CP, 10 patients had clinical and laboratory evidence of diabetes. Concerning CP complicated course were performed 14 resection and 11 draining operations on the pancreas. Based on clinical, instrumental and laboratory data was made the diagnosis of CP. Exocrine pancreatic function was assessed on the results of the breath test, using 13C-trioktanaine, which is applied for exocrine pancreatic function in vivo test. The content of C-peptide was investigated by enzyme-linked immunosorbent assay (ELISA). The data indicate pancreatic exocrine function decrease in patients with CP with complications and without complications in compare with the norm of 44% (24,3 +/- 1,7, 26,6 +/- 1,3%, respectively) according to the breath test. Significant decrease of the cumulative output tags based on the test data of patients with CP and pancreatic calcification, diabetes mellitus, after resection surgery with CP complications, and there were significant differences in compare with a group of patients with CP without complications (p = 0.5). The level of C-peptide in these groups of patients decreased significantly in compare with a group of patients with CP without complications, and patients with CP and Diabetes was reduced to 0,11 +/- 0,02 ng/ml, at a rate range of 0.7-1.9 ng/ml, ie below the minimum values of norm. Obtained a direct correlation between the level of C-peptide and indicators breath test in patients after resection HP (r = 0,84, p = 0,03). Antibodies to insulin in the whole group of studied patients CPs were negative, which proves the specific type of Diabetes at HP. Antibodies to insulin can be detected only at diabetes type 1. In 7 patients with CP and CD detected calcification, 5 patients performed resection surgery, 3 patients had calcification and conducted the pancreas resection. Thus, we can conclude that in patients with CP and formation of pancreas calcification, pancreas resections may predict the development of diabetes.

Topics: Adult; Aged; Blood Glucose; Breath Tests; C-Peptide; Diabetes Mellitus; Female; Gastrointestinal Agents; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Pancreatic Function Tests; Pancreatin; Pancreatitis, Chronic

Chronic pancreatitis (CP) in children is associated with significant morbidity and can lead to narcotic dependence. Total pancreatectomy (TP) may be indicated in refractory CP to relieve pain; simultaneous islet autotransplant (IAT) may prevent postsurgical diabetes. About half of pediatric patients are insulin independent 1 yr after IAT. Insulin independence correlates best with the number of islets available for transplantation (islet yield). Currently there is no known method to predict islet yield in a given patient. We assessed the ability of preoperative metabolic tests to predict islet yields in 10 children undergoing TP/IAT.. Hemoglobin A1c (HbA(1c)) and mixed meal tolerance tests (MMTT) were obtained prior to surgery in 10 patients age

Topics: Adolescent; Blood Glucose; C-Peptide; Carrier Proteins; Child; Child, Preschool; Creatinine; Cystic Fibrosis Transmembrane Conductance Regulator; Diabetes Mellitus, Type 1; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Pain, Intractable; Pancreatectomy; Pancreatitis, Chronic; Prospective Studies; Transplantation, Autologous; Treatment Outcome; Trypsin; Trypsin Inhibitor, Kazal Pancreatic

beta-Cell mass declines progressively during the course of diabetes, and various antidiabetic treatment regimens have been suggested to modulate beta-cell mass. However, imaging methods allowing the monitoring of changes in beta-cell mass in vivo have not yet become available. We address whether pancreatic beta-cell area can be assessed by functional test of insulin secretion in humans.. A total of 33 patients with chronic pancreatitis (n = 17), benign pancreatic adenomas (n = 13), and tumors of the ampulla of Vater (n = 3) at various stages of glucose tolerance were examined with an oral glucose load before undergoing pancreatic surgery. Indexes of insulin secretion were calculated and compared with the fractional beta-cell area of the pancreas.. beta-Cell area was related to fasting glucose concentrations in an inverse linear fashion (r = -0.53, P = 0.0014) and to 120-min postchallenge glycemia in an inverse exponential fashion (r = -0.89). beta-Cell area was best predicted by a C-peptide-to-glucose ratio determined 15 min after the glucose drink (r = 0.72, P < 0.0001). However, a fasting C-peptide-to-glucose ratio already yielded a reasonably close correlation (r = 0.63, P < 0.0001). Homeostasis model assessment (HOMA) beta-cell function was unrelated to beta-cell area.. Glucose control is closely related to pancreatic beta-cell area in humans. A C-peptide-to-glucose ratio after oral glucose ingestion appears to better predict beta-cell area than fasting measures, such as the HOMA index.

Topics: Adenoma; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Female; Hair Cells, Ampulla; Humans; Insulin; Insulin-Secreting Cells; Male; Pancreatic Neoplasms; Pancreatitis, Chronic

Total pancreatectomy is considered the final resort in the treatment of chronic pancreatitis; however, here we show that simultaneous islet autotransplantation can abrogate the onset of diabetes.. : In Leicester, 46 patients have now undergone total pancreatectomy with immediate islet auto transplant, and they have received a median of 2246 islet equivalent (IEQ)/kg body weight (range, 405-20,385 IEQ/kg body weight).. : Twelve patients have shown periods of insulin independence, for a median of 16.5 months (range, 2-63 months), and 5 remain insulin independent. Over the 10 years of follow-up, there has been a notable increase in insulin requirement per kilogram per day, and percentage of glycosylated hemoglobin levels have increased significantly (r = 0.66, P = 0.01). However, 100% of patients tested were C-peptide positive at their most recent assessment, and high fasting and stimulated C-peptide values recorded at 10 years after transplantation, 1.44 (range, 1.09-1.8 ng/mL) and 2.86 ng/mL (range, 1.19-4.53 ng/mL), respectively, suggest significant graft function in the long term. In addition, median serum creatinine has increased very little after the operation (71 nmol/L [range, 49-125 nmol/L] atpreoperation vs 76.5 nmol/L [range 72-81 nmol/L] at year 10), suggesting no diabetic nephropathy.. : Although there is a notable decline in islet function after islet auto transplant, there is still evidence of significant long-term insulin secretion and possible protection against diabetic complications.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Complications; Female; Follow-Up Studies; Glycated Hemoglobin; Graft Survival; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Pancreatectomy; Pancreaticoduodenectomy; Pancreatitis, Chronic; Time Factors; Transplantation, Autologous; Treatment Outcome

The incretin effect is reduced and the insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is abolished in patients with type 2 diabetes mellitus (T2DM).. To evaluate the causality of this deficiency we investigated 8 patients with chronic pancreatitis (CP) and normal glucose tolerance (NGT) (fasting plasma glucose (FPG): 5.5 (4.5-6.0) mM (mean (range); HbA(1c): 5.8 (5.4-6.3) %) and 8 patients with CP and secondary diabetes not requiring insulin (FPG: 7.1 (6.0-8.8) mM; HbA(1c): 7.0 (5.8-10.0) %) during three 15-mM hyperglycaemic clamps with continuous iv infusion of saline, glucagon-like peptide-1 (GLP-1) or GIP.. The initial (0-20 min) insulin and C-peptide responses were enhanced significantly in both groups by GLP-1 and GIP, respectively, compared to saline (P<0.05). In both groups GLP-1 infusion resulted in significantly greater insulin and C-peptide responses from 20-120 min compared with saline infusion. During GIP infusion the late-phase insulin response (20-120 min) was 3.1+/-1.0 fold greater than during saline infusion in the group of patients with CP and NGT (P<0.05), whereas there was no significant differences in patients with CP and DM.. The lack of GIP amplification of the late insulin response to iv glucose develops alongside the deterioration of glucose tolerance in patients with CP, suggesting that the same may be true for the loss of the GIP effect in patients with T2DM.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Incretins; Insulin; Male; Middle Aged; Pancreatitis, Chronic

Leptin alters pancreatic exocrine and beta-cell secretion in animal studies. We hypothesized that leptin might be important in the pathogenesis of idiopathic chronic pancreatitis (ICP) and/or the development of diabetes in ICP.. Fifty patients with ICP (25 with diabetes, 25 without diabetes) and 25 healthy controls were included in a prospective, case-control study. Fasting plasma leptin concentration was measured by enzyme-linked immunosorbent assay. Exocrine and endocrine pancreatic functions were assessed by fecal chymotrypsin and serum C-peptide, respectively. Anthropometric parameters and body fat mass (FM) were measured.. Patients with ICP (mean age, 30 years; 33 men) had significantly lower body mass index (19.5 +/- 2.6 kg/m2) and FM (10.6 +/- 4.2 kg) as compared with controls (body mass index, 21.7 +/- 4.1 kg/m2; FM, 19.0 +/- 16.6 kg; P < 0.01). Fecal chymotrypsin (median, 5.2 [range, 0.3-42.6] U/kg) and C-peptide (median, 1.7 [range, 0.2-9.5] ng/mL) were significantly lower in patients than in controls (12.9 [range, 2.5-33.0] U/kg and 3.5 [range, 0.3-10.3] ng/mL; P < 0.01). Plasma leptin concentration was slightly lower but statistically insignificant in patients with ICP (median, 4.0 [range, 2.0-62.5] ng/mL) as compared with controls (median, 5.0 [range, 2.0-63.0] ng/mL). Patients with and those without diabetes were also comparable with regard to their leptin concentration, pancreatic functions, and anthropometric parameters.. Leptin does not seem to have a pathophysiological role in either ICP or the development of diabetes in ICP.

Topics: Adipose Tissue; Adult; Anthropometry; C-Peptide; Case-Control Studies; Chymotrypsin; Diabetes Mellitus, Type 2; Feces; Female; Humans; Leptin; Male; Middle Aged; Pancreas, Exocrine; Pancreatitis, Chronic; Prospective Studies

Diabetes mellitus (DM) as part of chronic pancreatitis (ChP) belongs into the group of secondary DM with typical insulin deficiency. The prevalence and incidence of DM in ChP depends on the selected diagnostic criteria, geographical conditions and duration and grade of pancreatitis. Based on our findings during a 15-year investigation of impaired glucose tolerance and insulin secretion in patients with ChP the authors submit some partial (published and unpublished) results. The largest investigated group were 122 patients with ChP diagnosed according to the morphological appearance during ERCP. The authors detected a mutual close relationship between the extent of morphological damage of the efferent system of the pancreas on one hand and impaired glucose metabolism and endogenous insulin secretion on the other hand. It was revealed that values of C-peptide are in patients with ChP and normal glucose tolerance significantly lower as compared with the healthy population, and in patients with ChP and DM they are significantly lower as compared with non-obese type 2 diabetics. With the persistence of ChP the C-peptide levels decline gradually and the incidence of diabetes increases but even when DM persists in ChP C-peptide does not reach zero values as in type 1 DM. For detection of diabetes in ChP assessment of the fasting blood sugar level does not suffice and an oral glucose tolerance test must be made.

Topics: Adult; C-Peptide; Cholangiopancreatography, Endoscopic Retrograde; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatitis, Chronic