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Biomedical subjects

Reinhard G Bretzel

Publications and source records attributed to Reinhard G Bretzel.

At least 19 recordsLinked to original sources
PubMed2007

Pancreatin therapy in patients with insulin-treated diabetes mellitus and exocrine pancreatic insufficiency according to low fecal elastase 1 concentrations. Results of a prospective multi-centre trial.

BACKGROUND: Recently, high prevalence of exocrine dysfunction in diabetic populations has been reported. Patients with fecal elastase 1 concentration (FEC) <100 microg/g have also been demonstrated to suffer from steatorrhea in about 60% of cases, indicating the need of pancreatic enzyme replacement therapy. Until now, there have only been a few reports on the use of enzyme replacement therapy in diabetic patients with exocrine pancreatic insufficiency. This investigation was designed to evaluate the impact of enzyme-replacement therapy on glucose metabolism and diabetes treatment in a prospective study of insulin-treated patients with diabetes mellitus. METHODS: A total of 546 patients with diabetes mellitus requiring insulin treatment were screened for exocrine dysfunction by FEC measurements. One hundred and fifteen patients (21.1%) had FEC <100 microg/g (normal >200 microg/g). Of these, 95 patients entered the study and 80 patients were randomized to receive either pancreatin (Creon) (39 patients) or placebo (41 patients) in a double-blind manner. Parameters of glucose metabolism, diabetes therapy and clinical symptoms were recorded in standardized protocols for 16 weeks. RESULTS: During the observation phase of 16 weeks, there were no significant differences between both groups concerning HbA(1c), fasting glucose levels, 2-h pp glucose levels, clinical parameters and safety parameters. A reduction in mild and moderate hypoglycemia was observed in the pancreatin group at the end of the study. CONCLUSIONS: Pancreatin therapy can be used safely in patients with diabetes mellitus and exocrine dysfunction. Parameters of glucose metabolism were not improved by enzyme replacement therapy.

Diabetes Mellitus, Type 1↗
PubMed2006

Characterization of somatostatin receptor subtype-specific regulation of insulin and glucagon secretion: an in vitro study on isolated human pancreatic islets.

INTRODUCTION: Pancreatic A- and B-cells express somatostatin receptors (SSTRs). Five pharmacologically distinct SSTR subtypes are known (SSTR1-SSTR5). In rodents, SSTR2 inhibits glucagon secretion, whereas SSTR5 suppresses the release of insulin. Human pancreatic A- and B-cells express SSTR1-3 and SSTR5; however, their contribution to the regulation of glucagon and insulin secretion is not well known. AIM OF THE STUDY: The goal of this study was to characterize the role of individual SSTR subtypes in regulating human glucagon and insulin secretion in vitro. METHODS: Human pancreatic islets were isolated from healthy donors and incubated with somatostatin, SSTR1-3-selective and SSTR5-selective agonists, or an SSTR2-selective antagonist (DC-41-33). Stimulation of insulin secretion was induced by glucose (10, 20 mm) alone or in combination with 10 nm exendin-4 or 10 mm L-arginine. Glucagon secretion was induced by 20 mm L-arginine. Basal secretion of insulin and glucagon was measured at 2.8 or 3.3 mm glucose. RESULTS: SSTR1-, SSTR2-, and SSTR5-selective agonists inhibited insulin secretion with the following order of potency: SSTR2 (EC50, 0.08 nm) > SSTR5 (EC50, 5.3 nm) > SSTR1 (EC50, 35 nm). Glucagon secretion was inhibited by SSTR-selective agonists with the following order of potency: SSTR2 (EC50, 0.05 nm) > SSTR1 (EC50, 1.8 nm) > SSTR5 (EC50, 28 nm). DC-41-33 dose-dependently reversed the effects of the SSTR2-selective agonist on insulin and glucagon secretion. CONCLUSION: Our study demonstrates that SSTR2-agonist is the most potent inhibitor of insulin and glucagon secretion from isolated human pancreatic islets. Furthermore, we identify SSTR1- and SSTR5-selective agonists as additional inhibitors of insulin and glucagon secretion from human pancreas.

Arginine↗
PubMed2006

International trial of the Edmonton protocol for islet transplantation.

BACKGROUND: Islet transplantation offers the potential to improve glycemic control in a subgroup of patients with type 1 diabetes mellitus who are disabled by refractory hypoglycemia. We conducted an international, multicenter trial to explore the feasibility and reproducibility of islet transplantation with the use of a single common protocol (the Edmonton protocol). METHODS: We enrolled 36 subjects with type 1 diabetes mellitus, who underwent islet transplantation at nine international sites. Islets were prepared from pancreases of deceased donors and were transplanted within 2 hours after purification, without culture. The primary end point was defined as insulin independence with adequate glycemic control 1 year after the final transplantation. RESULTS: Of the 36 subjects, 16 (44%) met the primary end point, 10 (28%) had partial function, and 10 (28%) had complete graft loss 1 year after the final transplantation. A total of 21 subjects (58%) attained insulin independence with good glycemic control at any point throughout the trial. Of these subjects, 16 (76%) required insulin again at 2 years; 5 of the 16 subjects who reached the primary end point (31%) remained insulin-independent at 2 years. CONCLUSIONS: Islet transplantation with the use of the Edmonton protocol can successfully restore long-term endogenous insulin production and glycemic stability in subjects with type 1 diabetes mellitus and unstable control, but insulin independence is usually not sustainable. Persistent islet function even without insulin independence provides both protection from severe hypoglycemia and improved levels of glycated hemoglobin. (ClinicalTrials.gov number, NCT00014911 [ClinicalTrials.gov].).

Adult↗
PubMed2006

Glucose-dependent expansion of pancreatic beta-cells by the protein p8 in vitro and in vivo.

p8 protein expression is known to be upregulated in the exocrine pancreas during acute pancreatitis. Own previous work revealed glucose-dependent p8 expression also in endocrine pancreatic beta-cells. Here we demonstrate that glucose-induced INS-1 beta-cell expansion is preceded by p8 protein expression. Moreover, isopropylthiogalactoside (IPTG)-induced p8 overexpression in INS-1 beta-cells (p8-INS-1) enhances cell proliferation and expansion in the presence of glucose only. Although beta-cell-related gene expression (PDX-1, proinsulin I, GLUT2, glucokinase, amylin) and function (insulin content and secretion) are slightly reduced during p8 overexpression, removal of IPTG reverses beta-cell function within 24 h to normal levels. In addition, insulin secretion of p8-INS-1 beta-cells in response to 0-25 mM glucose is not altered by preceding p8-induced beta-cell expansion. Adenovirally transduced p8 overexpression in primary human pancreatic islets increases proliferation, expansion, and cumulative insulin secretion in vitro. Transplantation of mock-transduced control islets under the kidney capsule of immunosuppressed streptozotocin-diabetic mice reduces blood glucose and increases human C-peptide serum concentrations to stable levels after 3 days. In contrast, transplantation of equal numbers of p8-transduced islets results in a continuous decrease of blood glucose and increase of human C-peptide beyond 3 days, indicating p8-induced expansion of transplanted human beta-cells in vivo. This is underlined by a doubling of insulin content in kidneys containing p8-transduced islet grafts explanted on day 9. These results establish p8 as a novel molecular mediator of glucose-induced pancreatic beta-cell expansion in vitro and in vivo and support the notion of existing beta-cell replication in the adult organism.

Adenoviridae↗
PubMed2006

Pancreas storage in oxygenated perfluorodecalin does not restore post-transplant function of isolated pig islets pre-damaged by warm ischemia.

BACKGROUND: Cold storage in oxygenated perfluorodecalin (PFD) restores transplant function of ischemically damaged dog pancreata and reduces the impact of cold ischemia on recovery of isolated human islets. Whether PFD storage can improve islet isolation from pancreata exposed to significant warm ischemia (WI) is unclear yet. The present study aimed to clarify this question in adult pigs. METHODS: After exsanguination, the intestine was removed immediately or left in the cavity for 30 min of WI. Resected pancreata were intraductally flushed with cold University of Wisconsin solution. Subsequently, pancreata were processed immediately by digestion-filtration (group I: 0 min WI, n=6; II: 30 min WI, n=6) or first stored for 3 h in oxygenated PFD (III: 0 min WI+PFD, n=5; IV: 30 min WI+PFD, n=6). RESULTS: Pancreata subjected to 30 min of WI yielded significantly less islets compared with the corresponding non-ischemic organs (I vs. II, P<0.01; III vs. IV, P<0.05). Oxygenation did not ameliorate the loss in islet yield (II vs. IV, NS). Ischemic islets were characterized by depleted ATP stores (388+/-73 (I) vs. 133+/-22 ng/1000 IEQ (II), P<0.01) and diminished insulin response to glucose calculated as stimulation index (SI; 2.47+/-0.36 (I) vs. 0.25+/-0.17 (II), P<0.05). PFD storage of ischemic organs partially restored ATP content (217+/-23 ng/1000 IEQ, II vs. IV, P<0.05) and glucose SI (1.60+/-0.09, II vs. IV, P<0.05) to a significant extent that reached the level of corresponding PFD-stored, non-ischemic pancreata (III vs. IV, NS). Sustained normoglycemia was exclusively observed in diabetic nude mice transplanted with islets isolated from non-ischemic organs. The significantly reduced graft function of ischemic islets (I vs. II, III vs. IV, P<0.001) was not increased by pancreatic oxygenation (II vs. IV, NS). CONCLUSIONS: The present study suggests that pancreas short-term storage in oxygenated PFD improves in vitro but not the in vivo function of ischemically damaged pig islets.

Adenosine Triphosphate↗
PubMed2006

Diagnosis of mixed Plasmodium malariae and P. vivax infection in a development aid volunteer by examination of bone-marrow specimens by real-time PCR.

Mixed Plasmodium malariae and P. vivax infections in humans are reported very infrequently. The case of a 27-year-old male who sustained malaria quartana/tertiana caused by an unbalanced mixed P. malariae-P. vivax infection is reported here. Conventional tests and serology for malarial parasites were uniformly negative. Identification and quantification of the parasites were accomplished by examining bone-marrow specimens using specific real-time TaqMan PCR.

Adult↗
PubMed2006

Isolated pancreatic islets in three-dimensional matrices are responsive to stimulators and inhibitors of angiogenesis.

The formation of a new microvasculature is essential for the long-term survival and function of the islet graft. In this study we examined endothelium of isolated pancreatic islets by stimulation with growth factors, different culture conditions, and genetic modification. We also inspected the effect of immunosuppressives used in human transplantation on angiogenesis. Isolated islets were embedded in a three-dimensional fibrin or Matrigel matrix. The effect of hyperglycemia, hypoxia, and the addition of VEGF and bFGF was investigated. We exposed islets from transgenic mice expressing the VEGF gene (RIP1VEGF-A) to high glucose (16.7 mmol/L) medium and tested the immunosuppressive agents rapamycin (100 ng/ml) and FK506 (100 ng/ml). To quantify angiogenesis the percentage of sprouting islets was determined. New endothelial capillary-like structures protruded from isolated pancreatic islets. Addition of VEGF to the islets and transgenic RIP-VEGF islets showed a two- to threefold increase of sprouting islets compared to control. Hypoxic culture conditions stimulated angiogenesis, resulting in a twofold increase of capillary sprouting. Rapamycin and FK506 proved to be potent inhibitors of angiogenesis in this system, because a decrease of sprouting islets of more than 20% by both agents was observed. Isolated pancreatic islets are capable of forming new capillary structures and are susceptible to pro- and antiangiogenic stimuli.

Angiogenesis Inducing Agents↗
PubMed2006

Porcine islet graft function is affected by pretreatment with a caspase-3 inhibitor.

During the isolation procedure and after transplantation islets are subjected to numerous variables associated with the induction of apoptosis. The present study investigated the effect of transient pretreatment with caspase inhibitors on function and survival of transplanted pig islets. Isolated porcine islets (3000 IEQ) were incubated overnight in 200 microM of the caspase-3 inhibitor DEVD-CMK prior to transplantation into diabetic nude mice. Glucose-stimulated insulin release of pretreated islets was assessed during static incubation. DEVD-CMK successfully prevented the expression of capase-3 and DFF as demonstrated in heat-shocked pig islets. Nevertheless, transient pretreatment of freshly isolated pig islets with DEVD-CMK resulted in a significantly decreased final graft function of 50.0% (n = 16) compared to 85.7% (n = 14) in control islets (p < 0.05). Glucose-stimulated insulin release of porcine islets (n = 6) was not significantly effected by overnight culture with DEVD-CMK. Morphological assessment revealed that this caspase-3 inhibitor significantly increased the percentage of necrosis to a small, but nevertheless significant, extent in comparison to control islets (p < 0.05). The study demonstrates that short-time pretreatment with the caspase-3 inhibitor DEVD-CMK reduces the capacity of transplanted porcine islets to restore normoglycemia in diabetic nude mice.

Amino Acid Chloromethyl Ketones↗
PubMed2005

A potential important role of skeletal muscle in human counterregulation of hypoglycemia.

CONTEXT: During hypoglycemia, systemic glucose uptake (SGU) decreases and endogenous glucose release (EGR) increases. Skeletal muscle appears to be primarily responsible for the reduced SGU and may be important for the increased EGR by providing lactate for gluconeogenesis (GN). OBJECTIVE: The objective of the study was to test the hypothesis that reduced muscle glucose uptake and increased muscle lactate release both make major contributions to glucose counterregulation using systemic isotopic techniques in combination with forearm net balance measurements. SETTING: The study was conducted at the University of Giessen Clinical Research Center. PARTICIPANTS: Nine healthy volunteers participated in the study. INTERVENTION: A 2-h hyperinsulinemic euglycemic clamp (blood glucose approximately 4.4 mm) was followed by a 90-min hypoglycemic clamp (blood glucose approximately 2.6 mm). RESULTS: Compared with the euglycemic clamp, SGU decreased (21.0 +/- 2.0 vs. 29.6 +/- 1.8 micromol.kg body weight(-1).min(-1); P < 0.001), whereas EGR (11.2 +/- 1.7 vs. 4.9 +/- 1.3 micromol.kg body weight(-1) .min(-1); P < 0.003), arterial lactate concentrations (1051 +/- 162 vs. 907 +/- 115 microm; P < 0.02), systemic lactate release (23.5 +/- 0.9 vs. 17.1 +/- 0.9 micromol.kg body weight(-1).min(-1); P < 0.001), and lactate GN (4.50 +/- 0.60 vs. 2.74 +/- 0.30 micromol.kg body weight(-1).min(-1); P < 0.02) increased during hypoglycemia; the proportion of lactate used for GN remained unchanged (38 +/- 4 vs. 32 +/- 3%; P = 0.27). Whole-body muscle glucose uptake decreased approximately 50% during hypoglycemia (6.4 +/- 1.9 vs. 13.6 +/- 2.9 micromol.kg body weight(-1).min(-1); P < 0.001), which accounted for approximately 85% of the reduction of SGU. Whole-body muscle lactate release increased 6.6 +/- 1.6 micromol.kg body weight(-1). min(-1) (P < 0.01), which could have accounted for all the increase in systemic lactate release and, considering the proportion of lactate used for GN, contributed 1.4 +/- 0.4 micromol.kg body weight(-1).min(-1) (approximately 25%) to the increase in EGR. CONCLUSIONS: Reduced muscle glucose uptake and increased muscle lactate release both make major contributions to glucose counterregulation in humans.

Adult↗
PubMed2005

Vascular endothelial growth factor increases functional beta-cell mass by improvement of angiogenesis of isolated human and murine pancreatic islets.

BACKGROUND: Blood flow is impaired in islet transplants, but there is conflicting evidence on improving the outcome by promoting vascularization. We previously reported that islet endothelial cells (EC) possess significant angiogenic capacity. METHODS: To further address this issue, we studied human islets in culture under hypoxic conditions. Moreover, we used a transgene mouse model with human vascular endothelial growth factor (VEGF) production in beta-cells under the control of the rat insulin promoter (RIP) to stimulate islet EC proliferation. RESULTS: Subsequent to a hypoxic stimulus, islets responded with specific expression patterns of VEGF and fibroblast growth factor; however, this was not sufficient to prevent the decay of islet EC. VEGF release of RIP-VEGF transgenic islets was controlled by glucose and resulted in the formation of sprouts. When transplanted to the kidney capsule of diabetic mice, RIP-VEGF islets significantly enhanced microvascular density and functional blood flow to the graft compared with controls. CONCLUSIONS: Optimized angiogenesis of islet transplants resulted in greater availability of insulin caused by beta-cell proliferation and a significantly higher percentage (90% versus 20%) of mice cured from diabetes.

Adult↗
PubMed2005

Successful pancreas preservation by a perfluorocarbon-based one-layer method for subsequent pig islet isolation.

BACKGROUND: The oxygenation of human pancreas by the two-layer method (TLM) during cold storage was recently established for clinical islet transplantation. Simplification of TLM would facilitate the application of perfluorocarbon (PFC) as a regularly used preservation solution for subsequent islet transplantation. The present study examined whether PFC can be used in a one-layer method (OLM) for long-term pancreas preservation before isolation of adult pig islets. METHODS: Resected pancreases were intraductally flushed with cold University of Wisconsin solution and immediately processed (n=6) or subjected to 7-hour storage by OLM (n=8) or TLM (n=10). Subsequently, pancreases were intraductally distended with collagenase NB-8 supplemented with neutral protease. Isolation and purification were performed as previously described. RESULTS: Compared with unstored pancreases (3,670+/-740 islet equivalents [IEQ]) purified islet yield in TLM-stored organs (2,080+/-290 IEQ, P<0.05) was significantly decreased in contrast with OLM-preserved pancreases (3,110+/-520 IEQ, NS). No differences were observed between groups regarding purity (>90%), trypan-blue exclusion (>95%), adenosine triphosphate content, and mitochondrial viability of islets. Stimulation index during static glucose incubation (20 vs. 2.8 mm) was decreased after storage by TLM (1.81+/-0.20, P<0.05) but not by OLM (2.27+/-0.57) if compared with unstored pancreases (2.47+/-0.36). However, transplantation into diabetic nude mice resulted in sustained normoglycemia of recipients of either group until nephrectomy of graft-bearing kidneys was performed. CONCLUSIONS: This study demonstrates that PFC alone can be used in a one-layer procedure for successful pig-pancreas preservation. This simplification can facilitate the broad application of PFC as pancreas preservation solution without reducing its benefits demonstrated by TLM.

Adenosine↗
PubMed2005

Influence of collagenase loading on long-term preservation of pig pancreas by the two-layer method for subsequent islet isolation.

BACKGROUND: The introduction of the two-layer method (TLM) for long-term human pancreas preservation revealed the enormous potential of TLM to improve graft function of isolated islets. It is still unclear whether pig islets can be successfully isolated from pancreases after prolonged cold ischemia. To clarify this question, pig pancreases were subjected to 7-hour preservation by University of Wisconsin solution (UWS) storage or TLM. Another aim was to verify whether TLM can be synergistically combined with intraductal collagenase injection before cold storage. METHODS: After intraductal flush with UWS, organs were distended with 4.4 PZ-U/g of UWS-dissolved collagenase NB-8 and neutral protease adjusted to respectively 1.1, 0.2, 0.5, or 0.8 DMC-U/g for pancreases freshly procured (n=6) or distended with enzymes before (TLM preloaded, n=7) or after cold storage (UWS storage, n=4; TLM postloaded, n=10). RESULTS: Purified islet yield decreased from 429,200+/-86,700 islet equivalents (IEQ) in unstored pancreases to respectively 37,670+/-19620, 210,400+/-22900 and 238,000+/-26600 IEQ in UWS-stored (P<0.01), TLM-preloaded, or postloaded organs (P<0.05). Purity (>90%), viability (>95%), and insulin content were not different between groups. Islets from UWS-stored pancreases fragmented extensively, preventing further assessment of in vivo function. Compared with other experimental groups, islets from TLM-preloaded organs were characterized by enhanced basal and stimulated insulin release. Sustained normoglycemia was observed in diabetic nude mice transplanted with islets from TLM-postloaded or unstored pancreases in contrast with transient function in TLM-preloaded islets. CONCLUSIONS: This study demonstrates that significant amounts of intact pig islets can be isolated after prolonged pancreas preservation by TLM. Enzyme administration before TLM preservation decreases islet graft function.

Animals↗
PubMed2005

Effects of oral fat load on insulin output and glucose tolerance in healthy control subjects and obese patients without diabetes.

OBJECTIVE: Elevated plasma nonesterified fatty acid (NEFA) concentrations cause peripheral and hepatic insulin resistance and may play an important role in regulating glucose-induced insulin secretion. The aim of our study was to investigate the influence of physiologically elevated NEFA levels on glucose-stimulated insulin secretion in order to find evidence that NEFAs are a potential factor predisposing for type 2 diabetes and related metabolic disorders, which are known risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS: We combined an orally administered fat emulsion with an intravenous glucose tolerance test and measured the time course of NEFA, insulin, and glucose. In order to find pathological conditions we applied the experiment to healthy and obese subjects. RESULTS: The main findings are a significant increase in glucose-stimulated insulin secretion after oral fat load in both groups compared with the condition without preceding fat ingestion and a prolonged insulin secretion after fat load in obese patients compared with control subjects. CONCLUSIONS: The results provide evidence that fat ingestion modulates beta-cell function and that NEFA is a plausible mediator that acts as a link between fat and glucose metabolism by modulating glucose-stimulated insulin secretion. Under the condition of elevated plasma levels of NEFA, this mechanism may be responsible for hyperinsulinemia in obese patients and a potential target of type 2 diabetes prevention strategies.

Adult↗
PubMed2004

A direct efficacy and safety comparison of insulin aspart, human soluble insulin, and human premix insulin (70/30) in patients with type 2 diabetes.

OBJECTIVE: Because there are limited data on the comparison of insulin aspart and mixed insulin in type 2 diabetes, this trial was performed to compare the efficacy and safety of preprandial insulin aspart with human soluble insulin (HI) and human premix (70% NPH/30% regular) insulin (MIX). RESEARCH DESIGN AND METHODS: A total of 231 type 2 diabetic patients were randomized to insulin aspart (n = 75), HI (n = 80), or MIX (n = 76) for 3 months. Insulin aspart and HI were administered with or without bedtime NPH insulin. A total of 204 patients completed the trial according to protocol. HbA1c, 7-point blood glucose, insulin dosage, and hypoglycemic episodes were recorded. The primary end point was "change of HbA1c" from baseline to last visit. Analysis for equivalence was performed by t tests with three subtests. RESULTS: HbA1c decreased 0.91 +/- 1.00 for insulin aspart, 0.73 +/- 0.87 for HI, and 0.65 +/- 1.10 for MIX with the following confidence intervals: insulin aspart HI (-0.21 to 0.57, P = 0.025), insulin aspart MIX (-0.17 to 0.69, P = 0.092), and HI-MIX (-0.33 to 0.48, P = 0.006). Postprandial blood glucose decreased in the insulin aspart group: 0.44 mmol/l to >1.67 mmol/l compared with HI and 1.1 mmol/l to >1.67 mmol/l compared with MIX. Preprandial insulin doses were similar in the insulin aspart and HI groups (10-14.5 U). Hypoglycemic events per month were 0.56 HI, 0.40 insulin aspart, and 0.19 MIX. CONCLUSIONS: Statistically, insulin aspart was not equivalent to another treatment in terms of HbA1c reduction. Insulin aspart treatment resulted in improved HbA1c and postprandial blood glucose. The application of insulin aspart was safe and well tolerated.

Blood Glucose↗
PubMed2003

Randomised prospective study for the effect of therapy on residual beta cell function in type-1 diabetes mellitus [ISRCTN70703138].

BACKGROUND: Newly diagnosed insulin-dependent diabetes mellitus is characterised by a temporary recovery of endogeneous insulin ("remission") after the beginning of medical treatment with subcutaneous insulin injections. Although most diabetologists think, that insulin reserve is related to reduced occurrence of diabetic long-term complications, such as eye, nerve and kidney disease, there is only one prospective controlled clinical study (the DCCT) addressing this question, however as secondary hypothesis. METHODS/DESIGN: Therefore, we composed a trial consisting of two cohorts with two therapeutic options within each cohort (conventional versus intensive therapy) and a three-year follow-up. In one group the patients are randomly assigned to the treatment regimes to test the statistical alternative hypothesis if variable insulin dosage is superior to fixed insulin injection in preserving insulin reserve measured by C-peptide in serum. Another group includes patients who prefer one of the two therapies, decline randomisation, but consent to follow-up. Apart from the determination of insulin reserve as a biological parameter a second primary endpoint was defined as 'therapeutic failure' according to the criteria of the European Association for the Study of Diabetes. Patients pass a training program to help them self-manage diabetes. A standardised protocol is being set up to minimize centre effects and bias of health care providers. Potential patient dependent bias will be investigated by questionnaires measuring psychic coping processes of people with diabetes. Management of visit dates is directly navigated by the database. Automated visit-reminders are mailed to patients and caregivers to optimise the number of visits on schedule. Data quality is regularly monitored and centres are informed on the results of continuous data management.

Journal Article↗
PubMed2003

High prevalence of exocrine pancreatic insufficiency in diabetes mellitus. A multicenter study screening fecal elastase 1 concentrations in 1,021 diabetic patients.

BACKGROUND: There have been numerous reports on pancreatic exocrine dysfunction in diabetes mellitus using either direct or indirect function tests. The measurement of fecal elastase 1 concentrations (FEC) has been used as a screening tool for exocrine pancreatic disease in different patient groups indicating a high prevalence of exocrine dysfunction in diabetic populations. In this study we had the opportunity to study more than 1,000 diabetic patients to confirm recent observations in smaller populations. METHODS: FEC were measured by ELISA in 323 patients with type 1 and 697 type 2 diabetes mellitus. Subjects with a history of alcohol abuse, gastrointestinal surgery, cancer or inflammatory diseases were not included. Diabetes history and clinical data were recorded using a standard case report form. FINDINGS: 1,021 patients (334 female, 687 male; mean age 50 years; mean diabetes duration 11 years; mean age at onset of diabetes 39 years) were studied. FEC was normal (>200 microg/g) in 59.3% and severely reduced (<100 microg/g) in 22.9%. There were significant differences between type 1 and type 2 patients as well as between insulin-treated and non-insulin-treated patients. Furthermore, there were weak associations between FEC and diabetes duration, age at onset of diabetes and body mass index, respectively. INTERPRETATION: We could confirm that both type 1 and type 2 diabetic patients show pathological exocrine function in high prevalence. Exocrine insufficiency seems to be correlated to early onset of endocrine failure, long-lasting diabetes mellitus and low body mass index levels.

Adult↗
PubMed2003

[Apoptosis induced by free fatty acids].

BACKGROUND AND AIMS: Elevated free fatty acid (FFA) levels are believed to be one of the major contributing factors in the pathogenesis of type 2 diabetes. FFAs enhance peripheral insulin resistance, promote beta-cell dysfunction, and trigger beta-cell death. The purpose of this study was to investigate whether the lipoapoptotic effect of FFAs is determined by the degree of saturation and the chain length, and which pathways might be involved. MATERIAL AND METHODS: After incubation of RIN1046-38 rat insulinoma cells and primary human islet cells with different FFAs, apoptosis was assessed by flow cytometry (sub-G1-DNA formation) and TUNEL assay, respectively. Intracellular distribution of protein kinase C-delta (PKC-delta) was determined by confocal laser microscopy. RESULTS: In RIN1046-38 cells, the sub-G1 fraction increased 40-fold over basal (0.5% to approximately 20%) after treatment with the saturated FFAs palmitate and stearate (1 mM, 24 h), while the monounsaturated FFAs palmitoleate and oleate as well as the polyunsaturated FFA linoleate had no proapoptotic effect. Unsaturated FFAs even more prevented palmitate- and stearate-induced apoptosis completely. Furthermore, these results could be confirmed in primary beta-cells of human islets. Investigating potential underlying signaling pathways, it was found that only the saturated FFAs were able to induce nuclear translocation of PKC-delta. CONCLUSIONS: FFAs exert different effects on beta-cell survival. Saturated FFAs turned out to be pro-apoptotic, whereas unsaturated FFAs protected from saturated FFA-induced apoptosis. Furthermore, our data suggest an involvement of PKC-delta in apoptosis induced by saturated FFAs.

Cell Line↗