Glycemic management of diabetes by insulin therapy.

Recent technological innovations as insulin analogue formulation, devices for insulin delivery and glucose monitoring have allowed diabetic patients to improve their glycemic control and decrease their level of burden due to diabetes. Intensive insulin therapy via insulin pens, subcutaneous or intraperitoneal insulin infusions using pumps instead of vials and syringes, are associated with improved absorption reproducibility, HbA1c levels, reduced risk of hypo- or hyperglycemia, and increased quality of patient's life. These currently used systems are discussed in this review as well as the future of exogenous insulin therapy: closed loop system, the artificial pancreas, and oral insulin delivery. Glucose homeostasis is directly linked to glycemic regulated by portal insulin administration, thus endogenous insulin therapy might be the most promising treatment to "cure" diabetes. Consequently, pancreas and islet transplantation, and the bioartificial pancreas are described.

Design of a prospective, longitudinal cohort of people living with type 1 diabetes exploring factors associated with the residual cardiovascular risk and other diabetes-related complications: The SFDT1 study.

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.

Practical implementation of automated closed-loop insulin delivery: A French position statement.

Automated closed-loop (CL) insulin therapy has come of age. This major technological advance is expected to significantly improve the quality of care for adults, adolescents and children with type 1 diabetes. To improve access to this innovation for both patients and healthcare professionals (HCPs), and to promote adherence to its requirements in terms of safety, regulations, ethics and practice, the French Diabetes Society (SFD) brought together a French Working Group of experts to discuss the current practical consensus. The result is the present statement describing the indications for CL therapy with emphasis on the idea that treatment expectations must be clearly defined in advance. Specifications for expert care centres in charge of initiating the treatment were also proposed. Great importance was also attached to the crucial place of high-quality training for patients and healthcare professionals. Long-term follow-up should collect not only metabolic and clinical results, but also indicators related to psychosocial and human factors. Overall, this national consensus statement aims to promote the introduction of marketed CL devices into standard clinical practice.

Treatment of diabetes mellitus using an external insulin pump in clinical practice.

Before the initiation of insulin pump therapy, patients must be aware of the different aspects of this form of intensive insulin therapy. Most healthcare professionals recommend a sequential approach to inform patients about CSII. Factors that need to be considered in choosing an insulin pump include its safety features, durability of the device, tolerability and comfort of the catheter, user-friendliness, technical features and appearance. The initial insulin requirements need to be individualized for the given patient, using different methods to determine the appropriate dosages for the basal rate and prandial boluses. Glycaemic targets and algorithms for insulin dose adaptation need to be learned by the patients to enable them to avoid and/or correct hypo- and hyperglycaemia/ketosis episodes. Patients are also advised on how to carry out frequent self-monitoring of blood glucose-and of ketone bodies, if necessary. Insulin pumps are now able to deliver a range of basal rates and boluses that increase the flexibility of CSII. One specific issue is the approach to meal-planning, based on carbohydrate-counting or the equivalent: this method of so-called 'flexible insulin therapy' can improve metabolic control (for instance, by diminishing postprandial excursions) as well as the quality of life of patients. Evaluation of the knowledge and practices of the patient can be made through a continuous educational programme carried out by experienced nurses and physicians at the start of therapy and during follow-up. In addition, it may be necessary to identify the reasons for lack of improvement in metabolic control after several months of therapy, which include pump malfunction, cannula problems, miscalculated insulin dosages and insufficient metabolic control in specific clinical situations with a high risk of metabolic deterioration (illness, exercise, concomitant drugs). Annual assessment of the patient using an itemized checklist is required to verify the continued efficacy and safety of insulin pump therapy, two main factors of success with CSII treatment.

Treatment of diabetes mellitus using an external insulin pump: the state of the art.

The aim of diabetes treatment is to achieve tight glucose control to avoid the development of chronic diabetic complications while reducing the frequency of hypoglycaemic episodes. Continuous subcutaneous insulin infusion (CSII) using an external pump is an intensive diabetes therapy recognized to improve metabolic control and glycaemic instability, and to reduce the frequency of severe hypoglycaemia. For years, the theoretical advantages of the insulin pump (constancy of basal delivery, adjustable basal rates, and low insulin depots allowing the reduction of glycaemic variability) have contributed to its reported superiority compared with multiple daily injections (MDI). However, insulin pump therapy is now challenged by new MDI regimens based on long-acting insulin analogues that could replace the use of CSII. As a consequence, health professionals now have to determine which patients are likely to benefit the most from CSII. Recently, several studies reported that children and adolescents, and patients whose blood glucose imbalance was initially the most pronounced with basal-bolus regimens, would particularly benefit from CSII. Other indications were also proposed in marginal clinical situations with highly selected patients in whom a significant improvement of blood glucose was demonstrated. Finally, the use of CSII in type 2 diabetic patients now appears to be a good alternative to the ineffective MDI regimens observed in some of these patients. However, past experience with CSII indicates that candidates for insulin pump therapy must be carefully selected and strongly motivated to improve their glucose control. Use of CSII also requires strict medical supervision by physicians and a regular programme of patient education by paramedical teams, to ensure optimal responsible use of this technique by healthcare professionals.

Association of malignant insulinoma and type 2 diabetes mellitus: a case report.

We report a case of recurrent hypoglycemia due to malignant insulinoma in a type 2 diabetic patient correctly controlled for years with the same doses of oral antidiabetic agents. A 79-year-old woman was admitted for recurrent severe hypoglycemia. She had a history of type 2 diabetes since 2000. HbA1c was 7.8% when she reported mild hypoglycemia and 5.8% when recurrent hypoglycemia appeared despite progressive diminution of glicazide. Severe hypoglycemia continued despite interrupting diabetes medications. At admission, results showed inappropriately elevated insulin, C-peptide and proinsulin levels despite significant hypoglycemia. CT scan showed "cystic" nodes in the pancreas and in the liver. Liver biopsy found a well-differentiated neuroendocrine carcinoma with positive staining for chromogranin A and negative staining for insulin. Hypoglycemia improved with diazoxide, lanreotide and dextrose infusion. Liver chemoembolization was planned. Severe edema, dyspnea, hyponatremia, and hypo-osmolarity occurred. The patient's clinical status deteriorated rapidly with severe cardiac, renal and hepatic failure. She died in a few days. Association of diabetes mellitus and insulinoma is extremely rare. Malignant insulinoma survival is less than two years, shorter when hepatic localizations are present at diagnosis. Association of diabetes with insulinoma delays the diagnosis, but does not alter prognosis or favor carcinoma frequency. Lanreotide was inefficient in our patient despite good responses described in the literature. Heart, respiratory and renal failures have been described with diazoxide independently of the doses; this may in part explain the rapid death. Insulinoma should be considered as a cause of unusual and recurrent hypoglycemia in a diabetic patient especially if it persists after interrupting antidiabetic agents.

Practical implementation, education and interpretation guidelines for continuous glucose monitoring: A French position statement.

The use by diabetes patients of real-time continuous interstitial glucose monitoring (CGM) or the FreeStyle Libre® (FSL) flash glucose monitoring (FGM) system is becoming widespread and has changed diabetic practice. The working group bringing together a number of French experts has proposed the present practical consensus. Training of professionals and patient education are crucial for the success of CGM. Also, institutional recommendations must pay particular attention to the indications for and reimbursement of CGM devices in populations at risk of hypoglycaemia. The rules of good practice for CGM are the precursors of those that need to be enacted, given the oncoming emergence of artificial pancreas devices. It is necessary to have software combining user-friendliness, multiplatform usage and average glucose profile (AGP) presentation, while integrating glucose and insulin data as well as events. Expression of CGM data must strive for standardization that facilitates patient phenotyping and their follow-up, while integrating indicators of variability. The introduction of CGM involves a transformation of treatment support, rendering it longer and more complex as it also includes specific educational and technical dimensions. This complexity must be taken into account in discussions of organization of diabetes care.

Glargine blood biotransformation: in vitro appraisal with human insulin immunoassay.

AIM: Glargine, a long-acting insulin analogue, is metabolized in the bloodstream and in subcutaneous tissue. Glargine metabolism and its implications for diabetes therapy remain poorly understood. The aim of our study was to assess in vitro the glargine blood biotransformation and its inter-individual variability. METHODS: Formation of M1 glargine metabolite in vitro was studied with Elecsys Insulin immunoassay in pools of sera and sera from patients spiked with glargine. Elecsys Insulin assay is specific of human insulin, does not recognize glargine and its M2 metabolite but does recognize its M1 metabolite. RESULTS: Glargine incubation with serum resulted in M1 metabolite formation which was detected and characterized as an enzymatic process: metabolite kinetics were dependant on temperature, substrate concentration and serum proportion. Carboxypeptidase inhibitors and chelating agents partially inhibited the activity of the enzyme(s). Glargine biotransformation was decreased when blood was collected on EDTA tubes. After 30 min incubation of glargine (100 mU/l) in 69 sera at 37 degrees C, percentage of glargine converted into M1 ranged from 46% to 98% (mean 72%; S.D. 11%). CONCLUSION: Glargine blood biotransformation is an enzymatic process probably involving serum carboxypeptidase(s). Metabolite formation is rapid and non negligible. Inter-individual variability of glargine biotransformation is noteworthy and should be confronted to M1 metabolite bioactivity which has not been fully documented yet.

Efficacy of pioglitazone in familial partial lipodystrophy of the Dunnigan type: a case report.

A 25 year old woman consulted for a severe acanthosis nigricans and central distribution of fat. Her masculine type morphology was associated with muscular appearance of the limbs and excess fat deposits in the face and neck. Biological testing confirmed glucose intolerance associated with a severe insulin resistance, hypertriglyceridemia and polycystic ovary syndrome. The detection of a heterozygous missense mutation in LAMIN A/C gene at position 482 confirmed the diagnosis of Familial Partial Lipodystrophy (FPLD2). Due to a deterioration of clinical and metabolic status, 15 and then 30 mg per day of pioglitazone were added to her previous treatment with metformin, bezafibrate and omega-3 fatty acids. Metabolic status improved rapidly after 3 months and continued thereafter. Weight remained stable, body mass composition and waist circumference improved. After 18 months of treatment, glycaemia and triglycerides levels normalized, hepatic enzymes and liver echographic features improved. Insulin sensitivity improved dramatically with a HOMA % S value of 73% with metformin and of 98.2% when pioglitazone was added. Leptin levels increased from 6.6 to 10.2 microg/ml. We report a very rapid and good efficacy of pioglitazone added to metformin without side effects in FPLD2. If confirmed on more patients, early use of pioglitazone in association with metformin could be proposed in FPLD2.

Efficacy of short term continuous subcutaneous insulin lispro versus continuous intravenous regular insulin in poorly controlled, hospitalized, type 2 diabetic patients.

UNLABELLED: Intravenous insulin infusion (IVII) is rapidly effective in improving glycaemia in uncontrolled hospitalized diabetic patients. This significantly improves their morbidity and mortality. Intravenous insulin infusion may lead to IV infusion complications and is a heavy burden for caregivers. AIM: The aim of our work was to compare the efficacy of IV regular insulin versus lispro Continuous Subcutaneous Insulin Infusion (CSII), in improving glycaemia in patients hospitalized for uncontrolled type 2 diabetes, the efficacy being assessed on the average blood glucose level observed. METHODS: The study was designed as a prospective randomized study. Thirty-three type 2 diabetic patients, hospitalized for uncontrolled diabetes by their usual practitioner were included. After acceptation, patients were randomly assigned to lispro CSII (group 1, n=20) or IVII regular insulin (group 2, n=13) for 5 days. Ten capillary blood glucose/day were performed. Pre-meal blood glucose targets were 4.4-6.6 mmol/l. Mann Whitney, Wilcoxon and Fischer exact tests were used. RESULTS: BG levels decreased significantly (-3.4+/-0.55 mmol/l in group 1 and -3.60+/-0.55 mmol/l in group 2, P<0.01) during the first 12 hours. Mean daily blood glucose at day 5 was statistically improved in both groups compared to day 1 (P<0.05 Wilcoxon) and comparable between the 2 groups. No severe hypoglycaemia was reported. No catheter complications occurred in group 1, 7 occurred in group 2. CONCLUSION: CSII and IVII infusion were comparable in rapidly improving hyperglycaemia in uncontrolled type 2 diabetic patients. CSII, being more convenient, could be preferred in medical and surgical settings.

Continuous intraperitoneal insulin infusion does not increase the risk of organ-specific autoimmune disease in type 1 diabetic patients: results of a multicentric, comparative study.

AIM: The purpose of this national multicenter prospective study by the French EVADIAC group was to investigate the possibility that continuous intraperitoneal insulin infusion using an implanted pump (CIpii) increases the risk of autoimmune disease in type 1 diabetic patients as it increased anti-insulin immunogenicity. METHODS: Prevalence of clinical (Hashimoto's disease, hyperthyroidism, gastric atrophic disease and vitiligo) and subclinical (presence of anti-thyroperoxidase antibodies, anti-intrinsic factor antibodies, abnormal TSH levels) autoimmune diseases was estimated by comparing two groups of patients already treated by either CIpii (n=154) or external pump (CSII) (n=121) for an average of 6 years. Incidence of autoimmune disease was determined by comparing the same measurements one year after inclusion. RESULTS: No significant difference was observed for the total prevalence of clinical and subclinical auto-immune thyroid and gastric di-seases (35.6% and 3.2% respectively in the CIpii group versus 40.4% and 2.6% in the CSII group). No significant difference for the incidence of clinical and subclinical auto-immune diseases was observed: 7.2% and 0% in CIpii and 7.3% and 1.7% in CSII. CONCLUSION: As previously shown AIA (anti-insulin antibodies) levels were higher in CIpii than in CSII (32.9% vs 20.2%, P<0.0001) but no correlation was observed with either clinical or subclinical autoimmune disease. This large-scale study eliminates the possibility that CIpii increases the risk of autoimmune disease.

[Hyperglycemia and acute illness]. / Hyperglycémie et pathologies aiguës.

Hyperglycemia due to acute illness is frequently observed in non-diabetic patients. Considered as a physiological response to inflammation, it has now been shown to be an independent factor of morbid-mortality in critically ill patients. Hyperglycemia reduces the immune system response to aggression by decreasing the efficacy of some complement factors and polynuclear cells chemotactism and phagocytosis and by increasing the inflammatory response (cytokines, NF-kB and CRP). Glycemia near normalization using intensive insulin therapy significantly improves mortality and morbidity in several critical illnesses such as cardiac or infectious diseases. This improvement is probably due to the neutralization of deleterious effects caused by hyperglycemia and to the specific actions of insulin on the inflammatory response. Except for ICU patients, precise management protocols of hyperglycemia due to acute illness remain to be proposed and evaluated in clinical practice.

Improvement of islet graft function using liraglutide is correlated with its anti-inflammatory properties.

BACKGROUND AND PURPOSE: Liraglutide improves the metabolic control of diabetic animals after islet transplantation. However, the mechanisms underlying this effect remain unknown. The objective of this study was to evaluate the anti-inflammatory and anti-oxidative properties of liraglutide on rat pancreatic islets in vitro and in vivo. EXPERIMENTAL APPROACH: In vitro, rat islets were incubated with 10 µmol·L-1 liraglutide for 12 and 24 h. Islet viability functionality was assessed. The anti-inflammatory properties of liraglutide were evaluated by measuring CCL2, IL-6 and IL-10 secretion and macrophage chemotaxis. The anti-oxidative effect of liraglutide was evaluated by measuring intracellular ROS and the total anti-oxidative capacity. In vivo, 1000 islets were cultured for 24 h with or without liraglutide and then transplanted into the liver of streptozotocin-induced diabetic Lewis rats with or without injections of liraglutide. Effects of liraglutide on metabolic control were evaluated for 1 month. KEY RESULTS: Islet viability and function were preserved and enhanced with liraglutide treatment. Liraglutide decreased CCL2 and IL-6 secretion and macrophage activation after 12 h of culture, while IL-10 secretion was unchanged. However, intracellular levels of ROS were increased with liraglutide treatment at 12 h. This result was correlated with an increase of anti-oxidative capacity. In vivo, liraglutide decreased macrophage infiltration and reduced fasting blood glucose in transplanted rats. CONCLUSIONS AND IMPLICATIONS: The beneficial effects of liraglutide on pancreatic islets appear to be linked to its anti-inflammatory and anti-oxidative properties. These findings indicated that analogues of glucagon-like peptide-1 could be used to improve graft survival.

Impact of Pancreatic Rat Islet Density on Cell Survival during Hypoxia.

In bioartificial pancreases (BP), the number of islets needed to restore normoglycaemia in the diabetic patient is critical. However, the confinement of a high quantity of islets in a limited space may impact islet survival, particularly in regard to the low oxygen partial pressure (PO2) in such environments. The aim of the present study was to evaluate the impact of islet number in a confined space under hypoxia on cell survival. Rat islets were seeded at three different concentrations (150, 300, and 600 Islet Equivalents (IEQ)/cm(2)) and cultured in normal atmospheric pressure (160 mmHg) as well as hypoxic conditions (15 mmHg) for 24 hours. Cell viability, function, hypoxia-induced changes in gene expression, and cytokine secretion were then assessed. Notably, hypoxia appeared to induce a decrease in viability and increasing islet density exacerbated the observed increase in cellular apoptosis as well as the loss of function. These changes were also associated with an increase in inflammatory gene transcription. Taken together, these data indicate that when a high number of islets are confined to a small space under hypoxia, cell viability and function are significantly impacted. Thus, in order to improve islet survival in this environment during transplantation, oxygenation is of critical importance.

Impact of the Type of Continuous Insulin Administration on Metabolism in a Diabetic Rat Model.

Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC) injection in a basal and bolus scheme using insulin pens (injection) or pumps (preimplanted SC catheter). Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin) at the same dosage (4 IU/200 g/day) on rat metabolism and tissues. The rat weight and blood glucose levels were measured periodically after treatment. Immunostaining for signs of oxidative stress and for macrophages was performed on the liver and omental tissues. The continuous insulin delivery by pumps restored normoglycaemia, which induced the reduction of both reactive oxygen species and macrophage infiltration into the liver and omentum. Injections controlled the glucose levels for only a short period of time and therefore tissue stress and inflammation were elevated. In conclusion, the insulin administration mode has a crucial impact on rat metabolic parameters, which has to be taken into account when studies are designed.

Captopril-induced acute pancreatitis.

OBJECTIVE: To increase awareness concerning abdominal pain associated with the use of captopril, which is a molecule frequently used in diabetic patients. CASE: One case of acute pancreatitis associated with captopril, confirmed by a reintroduction, is described in a type II diabetes patient. CONCLUSIONS: Captopril and other angiotensin-converting enzyme inhibitors are very frequently prescribed in diabetic patients. Therefore, it is important to be aware of the possibility of pancreatitis linked to these molecules and to withdraw the treatment in case of severe unexplained abdominal pain.

Feasibility of intraperitoneal insulin therapy with programmable implantable pumps in IDDM. A multicenter study. The EVADIAC Study Group. Evaluation dans le Diabète du Traitement par Implants Actifs.

OBJECTIVE: To report the overall French experience, obtained through the collaboration of seven centers (EVADIAC [Evaluation dans le Diabète du Traitement par Implants Actifs] register), on the safety, feasibility, and efficacy of intraperitoneal insulin therapy by programmable implantable pumps, using three different devices. RESEARCH DESIGN AND METHODS: This is a multicenter prospective study involving 224 type I diabetic patients implanted with a programmable implantable pump (cumulative follow-up: 353 patient-years; mean duration: 1.5 +/- 0.9 years [mean +/- SD]. The Infusaid and the Promedos devices are equipped with a side port and refilled with U100 insulin (Hoechst 21 PH); the Minimed pump is not equipped with a side port and is refilled with U400 insulin (Hoechst 21 PH). Metabolic data and adverse events were recorded in a central register run by EVADIAC. RESULTS: A total of 29 local pump-pocket events (8/100 patient-years) and 9 pump failures (2.5/100 patient-years) occurred. The major technical problems were 1) pump flow rate reduction related to insulin aggregates, reversible after alkaline rinsing of the pump, and 2) 47 catheter obstructions requiring laparoscopic or conventional surgery. Pump therapy was abandoned in only 11 patients. HbA1c (7.4 +/- 1.8 vs. 6.8 +/- 1.0%, P < 0.001), mean glycemia (8.7 +/- 1.5 vs. 7.8 +/- 1.0 mmol/l, P < 0.001), and blood glucose SDs (3.8 +/- 0.8 vs. 3.3 +/- 0.8 mol/l, P < 0.001) decreased significantly after 6 months and remained lower than baseline thereafter. CONCLUSIONS: Intraperitoneal insulin infusion using an implantable programmable pump is a feasible and relatively safe technique that may improve metabolic control and glycemic stability. Long-term studies, however, are needed to demonstrate whether or not the improvement in glycemic control could be sustained for several years.

Improvement of HbA1c and blood glucose stability in IDDM patients treated with lispro insulin analog in external pumps.

OBJECTIVE: To compare the efficacy of the short-acting insulin analog lispro (LP) with that of regular insulin in IDDM patients treated with an external pump. RESEARCH DESIGN AND METHODS: Thirty-nine IDDM patients (age, 39.4 +/- 1.5 years; sex ratio, 22M/17W; BMI, 24.4 +/- 0.4 kg/m2; diabetes duration, 22.5 +/- 1.6 years) who were treated by external pump for 5.1 +/- 0.5 years were involved in an open-label, randomized, crossover multicenter study comparing two periods of 3 months of continuous subcutaneous insulin infusion with LP or with Actrapid HM, U-100 (ACT). Boluses were given 0-5 min (LP) or 20-30 min (ACT) before meals. Blood glucose (BG) was monitored before and after the three meals every day. RESULTS: The decrease in HbA1c was more pronounced with LP than with ACT (-0.62 +/- 0.13 vs. -0.09 +/- 0.15%, P = 0.01). BG levels were lower with LP (7.93 +/- 0.15 vs. 8.61 +/- 0.18 mmol/l, P < 0.0001), particularly postprandial BG levels (8.26 +/- 0.19 vs. 9.90 +/- 0.20 mmol/l, P < 0.0001). Standard deviations of all the BG values (3.44 +/- 0.10 vs. 3.80 +/- 0.10 mmol/l, P = 0.0001) and of postprandial BG values (3.58 +/- 0.10 vs. 3.84 +/- 0.10 mmol/l. P < 0.02) were lower with LP. The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly differ between LP and ACT (7.03 +/- 0.94 vs. 7.94 +/- 0.88 per month, respectively), but the rate of occurrences of very low BG, defined as BG < 2.0 mmol/l, were significantly reduced with LP (0.05 +/- 0.05 vs. 0.47 +/- 0.19 per month, P < 0.05). At the end of the study, all but two (95%) of the patients chose LP for the extension phase. CONCLUSIONS: When used in external pumps, LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes.

Substitution of insulin by exenatide in bad controlled type 2 diabetic patients: efficacy and predictive factors.

AIM: Exenatide therapy is indicated in type 2 diabetes after failure of oral antidiabetic agents (OAD). The aim of this observational prospective study was to assess efficacy of exenatide, in improving HbA1c of at least of 1% (responders) in type 2 diabetic patients treated previously with insulin. METHODS: Thirty-six patients (HbA1c >7.5%), with chronic bad glycemic control, were hospitalized to improve glycemia using transient continuous insulin infusion followed by administration of exenatide and OAD agents. In these patients, insulin had been introduced previously because of OAD failure without any sign of severe insulin deficiency. RESULTS: On the 27 patients analyzed at 3 months, 19 patients were responders (HbA1c: M0: 9.9±1.7%; M3: 7.6±1.2%). Among the 8 non-responders, only 4 deteriorated their HbA1c. After 9 months, 10 patients remained Responders (HbA1c: 7±0.9%). Predictive factors for an improvement of glycemic control were: diabetes duration shorter than 12 years, ratio fasting glycemia/C-peptide less than 1, fasting C-peptide higher than 2.0 µg/L and mean capillary blood glucose after 3 days of exenatide lower than 200 mg/dL. These criteria remained valid in case of a high HbA1c at baseline. CONCLUSION: In patients with no signs of insulin dependence and in case of insulin failure, exenatide associated to OAD may be tried in order to improve glycemic control, this objective was reached by 70% of our patients. Predictive factors for good response, easily available in clinical practice, may help therapeutic choices.

Impact of an autologous oxygenating matrix culture system on rat islet transplantation outcome.

Disruption of the pancreatic islet environment combined with the decrease in oxygen supply that occurs during isolation leads to poor islet survival. The aim of this study was to validate the benefit of using a plasma-based scaffold supplemented with perfluorodecalin to improve islet transplantation outcome. Rat islets were cultured in three conditions: i) control group, ii) plasma based-matrix (P-matrix), and iii) P-matrix supplemented with emulsified perfluorodecalin. After 24 h culture, matrix/cell contacts (Integrinß1, p-FAK/FAK, p-Akt/Akt), survival (caspase 3, TUNEL, FDA/PI), function, and HIF-1α translocation were assessed. Afterwards, P-matrices were dissolved and the islets were intraportally transplanted. Graft function was monitored for 31 days with glycaemia and C-peptide follow up. Inflammation was assessed by histology (macrophage and granulocyte staining) and thrombin/anti-thrombin complex measurement. Islet survival correlated with an increase in integrin, FAK, and Akt activation in P-matrices and function was maintained. Perfluorodecalin supplementation decreased translocation of HIF-1α in the nucleus and post-transplantation islet structure was better preserved in P-matrices, but a quicker activation of IBMIR resulted in early loss of graft function. "Oxygenating" P-matrices provided a real benefit to islet survival and resistance in vivo. However, intraportal transplantation is not suitable for this kind of culture due to IBMIR; thus, alternative sites must be explored.