Evaluation of Lipohypertrophy in Patients With Type 1 Diabetes Mellitus on Multiple Daily Insulin Injections or Continuous Subcutaneous Insulin Infusion

ObjectiveTo determine lipohypertrophy (LH) in patients with type 1 diabetes mellitus (T1DM) on multiple daily insulin injections (MDII) or continuous subcutaneous insulin infusion (CSII) and to reveal the factors associated with the development and severity of LH.MethodsSixty-six patients with T1DM treated with MDII (n = 35, 53%) or CSII (n = 31, 47%) for at least 1 year were included. LH localizations were detected with palpation and ultrasonography (USG).ResultsThe LH detection rate with USG was significantly higher than that by palpation in the whole group (P < .001). The LH was detected with USG in 30 (85.7%) patients in the MDII group and 22 (71.0%) patients in the CSII group (P = .144). Advanced LH was detected in 13 (37.1%) of the patients treated with MDII and in 3 (9.7%) of the patients treated with CSII. LH was more severe in the MDII group than in the CSII group (P = .013). Diabetes duration and length of infusion set use were significantly longer and body mass index, hypoglycemia, and complication rates were higher in patients with LH than those in patients without LH (P < .05). A positive correlation was found between LH severity and HbA1C and insulin dose (P < .05, for both). MDII as insulin administration method, incorrect rotation, and a history of ketosis were found to be the most related factors with LH severity in a multiple linear regression analysis (P < .05).ConclusionUSG might be an effective approach for detecting and evaluating the severity of LH. MDII might cause more severe LH than CSII in patients with T1DM. In this study, LH was found to be associated mostly with incorrect rotation technique and a history of ketosis.     

Tratamiento de la diabetes mellitus tipo 1 con implante pancreático de células madre adultas autólogas

Background and objectiveType 1 diabetes results from the autoimmune destruction of β cells in the pancreas. Several studies have discussed the ability of adult stem cells to differentiate and function effectively. The aim of this study was to attain fasting glycemia of < 100 mg/dl, or any glycemic value of < 200 mg/dl at any time in the course of the day, and a decrease of at least 50% in the dose of exogenous insulin administration up to 180 days after implantation, as well as C-peptide normalization.Patients and methodTwelve patients with type 1 diabetes mellitus were recruited for autologous bone marrow adult stem cell transplantation through an arterial catheter between October and December 2005. The catheterization was performed through the femoral artery, selectively to the inferior pancreatic artery with a microcatheter, and the implant was delivered to the distal segment. Age ranged between 21 and 60 years. Islet-cell and/or glutamic acid decarboxylase antibodies were negative, C-peptide levels were < 0.05 mg/ml, fasting glycemia was < 180 mg/dl, and glycosylated hemoglobin was < 9%.ResultsThe procedure was carried out uneventfully in all patients. Eleven patients (92%) discontinued the use of rapid-acting insulin and four patients managed total suppression of insulin therapy and showed normal C-peptide, glucose, and glycosylated hemoglobin values. Four patients received less than 66% of the initial total daily insulin dose with an increase in basal C-peptide values. Three patients received less than 50% of the initial total daily dose, with no changes in basal C peptide levels. Of these, two patients resumed initial insulin requirements. Only one patient showed no significant changes after transplantation. After 180 days, no adverse events had occurred.ConclusionsThe procedure is feasible and safe and recovery of gland function was obtained after stem cell implantation.     

Autologous bone marrow mononuclear cell therapy improves symptoms in patients with end-stage peripheral arterial disease and reduces inflammation-associated parameters

Background aimsThe purpose of this study was to evaluate the effect of autologous bone marrow mononuclear cells (BM-MNCs) on symptoms and perfusion indices in severely symptomatic patients with peripheral arterial disease (PAD) without further option for endovascular or surgical revascularization.MethodsOnly patients with severe symptomatic PAD (Fontaine class IIb-IV, Rutherford category 3–6) not amenable for revascularization were treated. Bone marrow from both cristae iliacae was harvested; MNCs were isolated by the Ficoll density-gradient method and transplanted by means of intra-arterial and intramuscular injection in the index limb. Functional (pain score, ulcer healing, maximum walking distance) and perfusion indices such as ankle-brachial-index and transcutaneous oxygen pressure were documented before and after BM-MNC therapy. Additionally, serum concentration of C-reactive protein and interleukin-6 were measured as markers of inflammation before and after BM-MNC treatment.ResultsSixteen consecutive patients (four women; mean age, 63.0 ± 13 years) were treated with a mean dose of 4.2 ± 2.2 × 10⁸ BM-MNCs. At 6 months' follow-up, ankle-brachial-index, transcutaneous oxygen pressure and maximum walking distance significantly increased, whereas C-reactive protein and interleukin-6 conversely decreased (P < 0.01 versus baseline values), resulting in 88% limb salvage, 75% pain reduction and 71% complete wound healing and/or reduction of ulcer size. One major and one minor amputation were performed, both in patients with Rutherford category 6.ConclusionsAutologous BM-MNC therapy in patients with end-stage PAD improves tissue perfusion indices and decreases markers of inflammation. If our observations could be confirmed by large-scale, randomized controlled trials, BM-MNC transplantation could become an alternative therapeutic option for patients with end-stage PAD.     

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced diabetes mellitus

ObjectiveTo better understand immune checkpoint inhibitor (ICI)-induced diabetes mellitus (DM) in cancer patients.Design and methodWe present a case of ICI-induced diabetic ketoacidosis (DKA) and conduct a systematic review of the PubMed and Web of Science databases up to September 2021 to identify all published cases of ICI-induced diabetes.ResultsIn addition to our case, a total of 171 published cases were identified during the literature search. Summary and statistical analyzes were conducted for all 172 cases. The median onset time from ICI initiation to DM diagnosis was 12 weeks (range: 0–122). DKA was present in 67.4% (116/172) of the cases, and low C-peptide levels were detected in 91.8% (123/134), indicating an acute onset of diabetes. Patients with positive glutamic acid decarboxylase antibodies (GADA) had an earlier onset of ICI-induced diabetes (median time 7 weeks vs. 16 weeks for GADA-negative patients, p < 0.001) and a higher frequency of DKA development (82.8 vs. 62.1%, p = 0.006). All but two patients developed insulin-dependent diabetes permanently. Immunotherapy rechallenge was reported in 53 cases after glycemia was well controlled.ConclusionICI-induced DM is a serious adverse event that often presents with life-threatening ketoacidosis. GADA positivity is related to an earlier onset of ICI-induced diabetes and a higher frequency of DKA development. Close monitoring of glucose levels is needed in patients receiving ICI treatment. ICI-induced DM is usually insulin-dependent since damage to β cells is irreversible. On the premise of well-controlled glycemia, immunotherapy rechallenge is feasible.     

Early endothelial progenitor cells in bone marrow are a biomarker of cell therapy success in patients with critical limb ischemia

Background aimsEndothelial progenitor cells (EPC) have been proposed for autologous angiogenic therapy. The objectives of this study were to quantify EPC in the peripheral blood and bone marrow mononuclear cells (BM-MNC) of patients with critical limb ischemia that had received BM-MNC as a cell therapy product, and to study the putative relationship between the presence of EPC and the process of neovascularization in toe or transmetatarsal amputation specimens.MethodsEarly and late endothelial progenitor cells (CFU-EC and ECFC) were cultivated and quantified according to published methods in peripheral blood and BM-MNC from patients with critical limb ischemia (CLI; n = 11) enrolled in the OPTIPEC trial (http://clinicaltrials.gov/ct2/show/NCT00377897) to receive BM-MNC as a cell therapy product.ResultsEight out of the 11 patients had undergone amputations. Three of the patients displayed a neoangiogenic process that was associated with a higher number of CFU-EC in BM-MNC, while CD3⁺, CFU-GM and CD34⁺ in BM-MNC, and EPC in peripheral blood, did not correlate with the appearance of newly formed vessels. As expected, circulating CFU-EC and ECFC counts were significantly lower in CLI patients compared with age-matched controls.ConclusionsIn patients with critical limb ischemia, EPC in peripheral blood were decreased compared with healthy individuals. However, in BM-MNC we found that relative numbers of CFU-EC could be used as an indicator to discriminate patients with neoangiogenic processes. These results need to be confirmed in a randomized study.     

IMPROVED HBA1C,TOTAL DAILY INSULIN DOSE,AND TREATMENT SATISFACTION WITH INSULIN PUMP THERAPY COMPARED TO MULTIPLE DAILY INSULIN INJECTIONS IN PATIENTS WITH TYPE 2 DIABETES IRRESPECTIVE OF BASELINE C-PEPTIDE LEVELS

Objective: Fasting C-peptide levels are used to differentiate type 1 from type 2 diabetes (T2D), thereby determining eligibility for coverage of continuous subcutaneous insulin infusion (CSII) for patients with T2D.Methods: A total of 168 patients (74 female/94 male, aged 55.5 ± 9.7 years) were randomized to CSII, and 163 patients (77 female/86 male, aged 56.4 ± 9.5 years) were randomized to multiple daily injections (MDI) of insulin and grouped by baseline C-peptide level: group A (≤183 pmol/L [≤0.55 ng/mL]); group B (>183 pmol/L [>0.55 ng/mL]). At 6 months, the MDI group crossed over to CSII. Within- and between-group comparisons were recorded at 6 and 12 months in the entire group and separately for those patients aged ≥65 years.Results: CSII reduced hemoglobin A1c (A1c) equally in groups A (P = .0006, P = .0022) and B (P<.0001, P<.0001) at 6 and 12 months, respectively. There was an increase in weight in group A versus group B at 6 months but not 12 months (P<.03). CSII therapy reduced total daily dose (TDD) of insulin and improved treatment satisfaction similarly in groups A and B. The results for patients aged ≥65 years displayed a similar trend as the entire group.Conclusion: A1c, TDD of insulin, and treatment satisfaction improved for T2D patients using CSII versus MDI therapy, irrespective of baseline C-peptide level. A subgroup of patients aged ≥65 years displayed a similar trend. These results support abandoning C-peptide as a criterion for reimbursing CSII therapy in patients with diabetes.Abbreviations: A1c = hemoglobin A1c; CMS = Centers for Medicare and Medicaid Services; CSII = continuous subcutaneous insulin infusion; DTSQ = Diabetes Treatment Satisfaction Questionnaire; MDI = multiple daily injections; RCT = randomized controlled trials; T1D = type 1 diabetes; T2D = type 2 diabetes; TDD = total daily dose     

Continuous Subcutaneous Pramlintide Infusion Therapy In Patients With Type 1 Diabetes: Observations From A Pilot Study

ObjectiveTo investigate the efficacy and safety of continuous (basal-bolus) subcutaneous pramlintide infusion (CSPI) in patients with type 1 diabetes mellitus.MethodsA 16-week, open-label, single-arm pilot study enrolled 11 patients (mean ± SD values: age, 39.9 ± 4.0 years; hemoglobin A1c, 8.20% ± 0.60%; weight, 92.3 ± 18.4 kg; body mass index, 29.7 ± 5.1 kg/m²) with longterm type 1 diabetes mellitus (20.7 ± 1.3 years; duration of pump therapy, 9.5 ± 6.0 years). Pramlintide basal infusion was begun with continuous subcutaneous infusion at 9 μg/h. After 3 days, premeal bolus doses of pramlintide were initiated at 15 μg and titrated to 60 μg per meal. Basal and bolus insulin doses were reduced 10% on initiation of CSPI and adjusted thereafter as needed to prevent hypoglycemia.ResultsAfter 16 weeks of pramlintide therapy, mean ± SD hemoglobin A1c decreased to 7.85% ± 0.74% (-0.35%). The fasting glucose level declined from 198.2 ± 66.9 mg/dL to 135.8 ± 63.9 mg/dL. The mean weight decreased to 91.8 ± 20.1 kg (-0.5 kg) at week 12. The daily bolus insulin requirement decreased 20%; daily basal insulin was unchanged (27.7 ± 11.7 U). All patients experienced mild postprandial hypoglycemia, but no severe hypoglycemia was reported. Three of the 11 study participants experienced mild initial nausea, but all patients successfully titrated bolus doses to 60 μg within 3 weeks.ConclusionIn this pilot study of 11 patients with type 1 diabetes using insulin pumps, CSPI seemed safe and well tolerated, did not alter pramlintide pharmacokinetic variables, and reduced fasting glucose levels. Larger studies of this method for pramlintide administration seem warranted. (Endocr Pract. 2009;15:689-695)     

Patient Outcomes after Implementation of a Protocol for Inpatient Insulin Pump Therapy

ObjectiveTo determine the safety and the results of use of an inpatient insulin pump protocol (IIPP).MethodsIn this quality improvement initiative, review of medical records of bedside capillary blood glucose (CBG) levels and pump-related adverse events was performed on 50 consecutive inpatients admitted to the hospital with continuous subcutaneous insulin infusion (CSII) after implementation of our IIPP. Patients were categorized in 3 groups on the basis of evidence in the medical records for IIPP in combination with inpatient diabetes service consultation (group 1; n = 34), for IIPP alone (group 2; n = 12), or for usual care (group 3; n = 4). Patients identified during hospital admission as using CSII therapy were invited to complete a satisfaction questionnaire for inpatient CSII use.ResultsMean CBG levels were similar among the 3 groups (groups 1, 2, and 3: 173 ± 43 mg/dL versus 187 ± 62 mg/dL versus 218 ± 46 mg/dL, respectively). Although there were more patient-days with blood glucose > 300 mg/ dL in group 3 (P = .02), there were no significant group differences in the frequency of hypoglycemia (CBG < 70 mg/ dL). Only 1 pump malfunction and 1 infusion site problem were reported among all study patients. No serious adverse events related to CSII therapy occurred. The majority of patients (86%) reported satisfaction with their ability to continue CSII use in the hospital.ConclusionPatients using CSII as outpatients are candidates for inpatient diabetes self-management. Inexperience with these devices on the part of hospital personnel together with the limited studies of patient experience with CSII in the hospital contributes to inconsistencies in management of these patients. An IIPP provides a standardized and safe approach to the use of CSII in the hospital. (Endocr Pract. 2009;15:415-424)     

Atypical Diabetes Mellitus Associated with Bone Marrow Transplantation

ObjectiveTo describe 3 cases of atypical diabetes mellitus following bone marrow transplantation.MethodsWe describe the clinical presentation and relevant laboratory findings of 3 patients who presented with new-onset diabetes mellitus after bone marrow transplantation and discuss the possible mechanisms.ResultsA 52-year-old white man with chronic myelogenous leukemia, a 51-year-old white woman with acute myelogenous leukemia, and a 38-year-old Hispanic woman with acute myelogenous leukemia presented with acute onset of diabetes mellitus after bone marrow transplantation. Although blood glucose levels were initially very high, the patients required only small insulin dosages for glycemic control. Both the acute onset and requirement of relatively small insulin dosages were characteristic of type 1 diabetes mellitus. Onset of diabetes appeared to be unrelated to immunosuppressive drug therapy because it happened several months after starting these drugs. C-peptide was detectable, and glutamic acid decarboxylase antibodies were absent. Diabetes mellitus remitted spontaneously after a few months while the immunosuppressive drugs were continued.ConclusionAlthough the underlying mechanisms are unknown, cytokine changes after bone marrow transplantation may have led to temporary b-cell dysfunction in these patients. (Endocr Pract. 2010;16:93-96)     

Ketosis-Prone Type 2 Diabetes: Effect of Hyperglycemia on β-Cell Function and Skeletal Muscle Insulin Signaling

ObjectiveTo determine the underlying mechanism for the severe and transient β-cell dysfunction and impaired insulin action in obese African American patients with ketosis-prone diabetes.MethodsThe effect of sustained hyperglycemia (glucotoxicity) and increased free fatty acids (lipotoxicity) on β-cell function was assessed by changes in insulin secretion during a 20-hour glucose (200 mg/m² per minute) and a 48-hour Intralipid (40 mL/h) infusion, respectively. Insulin-activated signaling pathways and pattern of Akt-1 and Akt-2 expression and insulin-stimulated phosphorylation were analyzed in skeletal muscle biopsy specimens. Studies were performed in an obese African American woman within 48 hours after resolution of diabetic ketoacidosis and 1 week after discontinuation of insulin treatment.ResultsDextrose infusion rapidly increased C-pep-tide levels from a baseline of 3.2 ng/mL to a mean of 7.1 ± 0.5 ng/mL during the first 8 hours of infusion; thereafter, C-peptide levels progressively declined. Lipid infusion was not associated with any deleterious effect on insulin and C-peptide secretion. Initial in vitro stimulation of muscle tissue with insulin resulted in a substantial and selectively decreased Akt-2 expression and insulin-stimulated phosphorylation on the serine residue. Improved metabolic control resulted in 70% greater Akt expression at near-normoglycemic remission in comparison with the period of hyperglycemia.ConclusionHyperglycemia, but not increased free fatty acid levels, led to progressive β-cell dysfunction and impaired insulin secretion. Hyperglycemia was also associated with diminished skeletal muscle Akt expression and phosphorylation in an African American woman with ketosis-prone diabetes, and this defect improved notably with aggressive insulin therapy. These results indicate the importance of glucose toxicity in the pathogenesis of keto-sis-prone diabetes in obese African American patients. (Endocr Pract. 2007;13:283-290)     

Severe Hyponatre mia Due to Rosiglita zone Use in an Elderly Woman With Diabetes Mellitus: A Rare Cause of Syndrome of Inappropriate Antidiuretic Hormone Secretion

ObjectiveTo describe the first case of syndrome of inappropriate antidiuretic hormone secretion with lifethreatening hyponatremia due to rosiglitazone therapy.MethodsWe describe the clinical, laboratory, and imaging findings of the study patient.ResultsAn 89-year-old woman with a 5-year history of type 2 diabetes mellitus was admitted to the emergency department because of unconsciousness. She had reported generalized weakness for 15 days and nausea and vomiting for 3 days. Findings from laboratory analysis showed severe hyponatremia (sodium, 110 mEq/L). She had normal renal, cardiac, and adrenal function, and she did not have edema or volume depletion. The cause of hyponatremia was syndrome of inappropriate antidiuretic hormone secretion. We did not find any cause for her condition other than rosiglitazone, an antihyperglycemic drug that is increasingly being used in patients with type 2 diabetes mellitus. According to her medical history, rosiglitazone was prescribed 1 month previously after withdrawal of gliclazide. We stopped the rosiglitazone and administered hypertonic saline infusion to treat the hyponatremia. Saline infusion was stopped and blood sodium levels were stabilized in the normal range after 2 days. The patient’s plasma sodium concentration has remained in the reference range at follow-up visits.ConclusionsThis is the first reported case of syndrome of inappropriate antidiuretic hormone secretion as an adverse effect of rosiglitazone, and this drug should possibly be considered for addition to the list of drugs that cause this condition. (Endocr Pract. 2008;14:1017-1019)     

Cell therapy with bone marrow stromal cells after intracerebral hemorrhage: impact of platelet-rich plasma scaffolds

Background aimsCell therapy using bone marrow stromal cells (BMSCs) has been considered a promising strategy for neurologic sequelae after intracerebral hemorrhage (ICH). However, after intracerebral administration of BMSCs, most of the cells die, partly because of the absence of extracellular matrix. Intracerebral transplantation of BMSCs, supported in a platelet-rich plasma (PRP) scaffold, optimizes this type of cell therapy.MethodsICH was induced by stereotactic injection of 0.5 IU of collagenase type IV in the striatum of adult Wistar rats (n = 40). Two months later, the rats were subjected to intracerebral administration of 5 × 10⁶ allogeneic BMSCs embedded in a PRP scaffold (n = 10), 5 × 10⁶ allogeneic BMSCs in saline (n = 10), PRP-derived scaffold only (n = 10) or saline only (n = 10). Functional improvements in each group over the next 6 months were assessed using Rotarod and Video-Tracking-Box tests. Endogenous neurogenesis and survival of transplanted BMSCs were examined at the end of follow-up.ResultsOur study demonstrated neurologic improvement after BMSC transplantation and significantly better functional improvement for the group of animals that received BMSCs in the PRP-derived scaffold compared with the group that received BMSCs in saline. Histologic results showed that better functional outcome was associated with strong activation of endogenous neurogenesis. After intracerebral administration of BMSCs, donor cells were integrated in the injured tissue and showed phenotypic expression of glial fibrillary acidic protein and neuronal nucleus.ConclusionsPRP-derived scaffolds increase the viability and biologic activity of BMSCs and optimize functional recovery when this type of cell therapy is applied after ICH.     

Differences in motor unit behavior during isometric contractions in patients with diabetic peripheral neuropathy at various disease severities

The aim of this study was to determine whether HD-sEMG is sensitive to detecting changes in motor unit behavior amongst healthy adults and type 2 diabetes mellitus (T2DM) patients presenting diabetic peripheral neuropathy (DPN) at different levels. Healthy control subjects (CON, n = 8) and T2DM patients presenting no DPN symptoms (ABS, n = 8), moderate DPN (MOD, n = 18), and severe DPN (SEV, n = 12) performed isometric ankle dorsiflexion at 30 % maximum voluntary contraction while high-density surface EMG (HD-sEMG) was recorded from the tibialis anterior muscle. HD-sEMG signals were decomposed, providing estimates of discharge rate, motor unit conduction velocity (MUCV), and motor unit territory area (MUTA). As a result, the ABS group presented reduced MUCV compared to CON. The groups with diabetes presented significantly larger MUTA compared to the CON group (p < 0.01), and the SEV group presented a significantly lower discharge rate compared to CON and ABS (p < 0.01). In addition, the SEV group presented significantly higher CoV_force compared to CON and MOD. These results support the use of HD-SEMG as a method to detect peripheral and central changes related to DPN.     

Reproducible preparation of spheroids of pancreatic hormone positive cells from human iPS cells: An in vitro study

BackgroundTransplantation of islets of Langerhans is regarded as a promising therapy for type 1 diabetes. A large number of β-cells are required for the treatment of human type 1 diabetes. Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, have been considered as new sources for cell replacement therapy.MethodsCell aggregates were prepared from human iPS cells using agarose microwell plates and differentiated into pancreatic endocrine cells by changing the culture media with different additives.ResultsAfter 20 days of culture, approximately 30% of cells in aggregates were positive for C-peptide. After another 14 days in culture, the cells gained an ability to alter C-peptide release in response to changes in the glucose concentration.ConclusionsUniform aggregates of human iPSCs were easily prepared on agarose microwell plates and efficiently differentiated into the pancreatic endocrine lineage. Thus, aggregate culture is a suitable method for preparing islet-like aggregates from human iPSCs.General significanceOur results indicate that the microwell plate is suitable for scaling up the preparation of pancreatic endocrine cells from human iPS cells in a robotic system.     

Safety and Efficacy of Exenatide in Combination with Insulin in Patients with Type 2 Diabetes Mellitus

ObjectiveTo evaluate the 1-year efficacy and safety of treatment with exenatide in combination with insulin (a use not approved by the US Food and Drug Administration).MethodsElectronic medical records of 3 private-practice endocrinologists were reviewed to identify patients with type 2 diabetes mellitus (T2DM) receiving insulin who subsequently began exenatide therapy. Patients’ baseline hemoglobin A1c (A1C) levels, weights, lipid profiles, blood pressures, and medication utilization were compared with corresponding data obtained after a minimal duration of 12 months.ResultsWe identified 134 patients with T2DM initiating exenatide therapy in combination with insulin between April 2005 and April 2006. One-year follow-up information was available for 124 patients. Exenatide use resulted in a significant 0.87% reduction in A1C (P < .001), despite a 45% discontinuation of premeal insulin use (P < .001), a 9-U reduction in mean premeal insulin doses (P = .0066), a reduction in the median number of daily insulin injections from 2 to 1 (P = .0053), and a 59% discontinuation rate of sulfonylurea use (P = .0088). Exenatide use was associated with a mean weight loss of 5.2 kg (P < .001), with 72% of evaluable patients losing weight. Forty-eight patients (36%) discontinued exenatide therapy during the first year, primarily attributable to gastrointestinal intolerance. Fourteen patients (10%) experienced hypoglycemia, most of which was mild.ConclusionExenatide in combination with insulin in patients with T2DM was associated with significant reductions in A1C and weight after 1 year of therapy. This was offset, however, by an exenatide discontinuation rate of 36%, primarily due to adverse gastrointestinal effects. (Endocr Pract. 2008;14:285-292)     

Safety and Efficacy of Percutaneous Mitral Valve Repair Using the MitraClip? System in Patients with Diabetes Mellitus

Background

Patients with diabetes mellitus show a negative outcome in percutaneous coronary intervention, aortic valve replacement and cardiac surgery. The impact of diabetes on patients undergoing treatment of severe mitral regurgitation (MR) using the MitraClip system is not known. We therefore sought to assess whether percutaneous mitral valve repair with the MitraClip system is safe and effective in patients with diabetes mellitus.

Methods and Results

We included 58 patients with severe and moderate-to-severe MR in an open-label observational single-center study. Ninteen patients were under oral medication or insulin therapy for type II diabetes mellitus. MitraClip devices were successfully implanted in all patients with diabetes and in 97.4% (n = 38) of patients without diabetes (p = 0.672). Periprocedural major cardiac adverse and cerebrovascular events (MACCE) occurred in 5.1% (n = 2) of patients without diabetes whereas patients with diabetes did not show any MACCE (p = 0.448). 30-day mortality was 1.7% (n = 1) with no case of death in the diabetes group. Short-term follow up of three months showed a significant improvement of NYHA class and quality of life evaluated by the Minnesota Living with Heart Failure Questionnaire in both groups, with no changes in the 6-minute walk test.

Conclusions

Mitral valve repair with the MitraClip system is safe and effective in patients with type II diabetes mellitus.

Trial Registration

MitraClip Registry {"type":"clinical-trial","attrs":{"text":"NCT02033811","term_id":"NCT02033811"}}NCT02033811     

Variations in novel cellular therapy products manufacturing

Background aimsAt the frontier of transfusion medicine and transplantation, the field of cellular therapy is emerging. Most novel cellular therapy products are produced under investigational protocols with no clear standardization across cell processing centers. Thus, the purpose of this study was to uncover any variations in manufacturing practices for similar cellular therapy products across different cell processing laboratories worldwide.MethodsAn exploratory survey that was designed to identify variations in manufacturing practices in novel cellular therapy products was sent to cell processing laboratory directors worldwide. The questionnaire focused on the manufacturing life cycle of different cell therapies (i.e., collection, purification, in vitro expansion, freezing and storage, and thawing and washing), as well as the level of regulations followed to process each product type.ResultsThe majority of the centers processed hematopoietic progenitor cells (HPCs) from peripheral blood (n = 18), bone marrow (n = 16) or cord blood (n = 19), making HPCs the most commonly processed cells. The next most commonly produced cellular therapies were lymphocytes (n = 19) followed by mesenchymal stromal cells (n = 14), dendritic cells (n = 9) and natural killer (NK) cells (n = 9). A minority of centers (<5) processed pancreatic islet cells (n = 4), neural cells (n = 3) and induced-pluripotent stem cells (n = 3). Thirty-two laboratories processed products under an investigational status, for either phase I/II (n = 27) or phase III (n = 17) clinical trials. If purification methods were used, these varied for the type of product processed and by institution. Environmental monitoring methods also varied by product type and institution.ConclusionThis exploratory survey shows a wide variation in cellular therapy manufacturing practices across different cell processing laboratories. A better understanding of the effect of these variations on the quality of these cell-based therapies will be important to assess for further process evaluation and development.     

地特胰岛素联合二甲双胍治疗妊娠糖尿病的疗效及对患者血清内脂素、抵抗素、血脂水平的影响

目的:研究地特胰岛素联合二甲双胍治疗妊娠糖尿病的临床疗效及对患者血清内脂素、抵抗素、血脂水平的影响。方法:选择2016年10月至2017年10月在我院进行治疗的妊娠糖尿病患者120例,按照随机数表法分为观察组和对照组。对照组给予二甲双胍治疗,观察组以对照组为基础联合地特胰岛素治疗。治疗后,观察和两组的临床疗效及不良反应的发生情况,治疗前后血清内脂素、抵抗素水平以及血脂血糖水平的变化。结果:治疗后,观察组总有效率(96.67%)明显高于对照组(85.00%)(P0.05);观察组血清内脂素、抵抗素、总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖及餐后2h血糖水平均显著低于对照组(P0.05),HDL-C水平明显高于对照组(P0.05);两组不良反应发生率比较差异无统计学意义(P0.05)。结论:与单用二甲双胍相比,地特胰岛素联合二甲双胍治疗妊娠糖尿病可有效调节患者血脂血糖水平,降低血清内脂素与抵抗素水平,从而显著提高临床疗效,且安全性较好。     

C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients

Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol.kg-1.min-1) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 microg.kg-1.min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower (P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion (P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients.