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Yoeri M Luijf,
Julia K Mader,
Werner Doll,
Thomas Pieber,
Anne Farret,
Jerome Place,
Eric Renard,
Daniela Bruttomesso,
Alessio Filippi, Angelo Avogaro,
Sabine Arnolds,
Carsten Benesch,
Lutz Heinemann,
J Hans Devries On Behalf Of The Ap Home Consortium
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ABSTRACT: Abstract Objective: This study assessed the accuracy and reliability of three continuous glucose monitoring (CGM) systems. Research Design and Methods: We studied the Animas(®) (West Chester, PA) Vibe™ with Dexcom(®) (San Diego, CA) G4™ version A sensor (G4A), the Abbott Diabetes Care (Alameda, CA) Freestyle(®) Navigator I (NAV), and the Medtronic (Northridge, CA) Paradigm(®) with Enlite™ sensor (ENL) in 20 patients with type 1 diabetes mellitus. All systems were investigated both in a clinical research center (CRC) and at home. In the CRC, patients received a meal with a delayed and increased insulin dose to induce a postprandial glucose peak and nadir. Hereafter, randomization determined which two of the three systems would be worn at home until the end of functioning, attempting use beyond manufacturer-specified lifetime. Patients performed at least five reference finger sticks per day. An analysis of variance was performed on all data points ≥15 min apart. Results: Overall average mean absolute relative difference (MARD) (SD) measured at the CRC was 16.5% (14.3%) for NAV and 16.4% (15.6%) for ENL, outperforming G4A at 20.5% (18.2%) (P<0.001). Overall MARD when assessed at home was 14.5% (16.7%) for NAV and 16.5 (18.8%) for G4A, outperforming ENL at 18.9% (23.6%) (P=0.006). Median time until end of functioning was similar: 10.0 (1.0) days for G4A, 8.0 (3.5) days for NAV, and 8.0 (1.5) days for ENL (P=0.119). Conclusions: In the CRC, G4A was less accurate than NAV and ENL sensors, which seemed comparable. However, at home, ENL was less accurate than NAV and G4A. Moreover, CGM systems often show sufficient accuracy to be used beyond manufacturer-specified lifetime.
Diabetes Technology & Therapeutics 05/2013; · 1.93 Impact Factor
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Yoeri M Luijf,
Sabine Arnolds, Angelo Avogaro,
Carsten Benesch,
Daniela Bruttomesso,
Anne Farret,
Lutz Heinemann,
Jerome Place,
Eric Renard,
Rachele Scotton,
J Hans Devries On Behalf Of The Ap Home Consortium
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ABSTRACT: Abstract Background and Aims: The aim of this study was to compare blood glucose and plasma insulin profiles after bolus insulin infusion by a patch pump (PP) versus a conventional pump (CP), directly after placement and after Day 3 of use. Patients and Methods: Twenty patients with type 1 diabetes came in for two blocks of visits: one block of two visits while wearing the OmniPod(®) (Insulet Corp., Bedford, MA) insulin pump (PP) and one block of two visits while wearing the Medtronic Diabetes (Northridge, CA) Paradigm(®) pump (CP). Patients administered an identical mealtime insulin bolus of at least 6 IU. Results: For PP, maximum glucose levels were 28.7% lower on Day 3 (P=0.020), when maximum insulin levels were 30.3% higher (P=0.002). For CP, maximum glucose levels were 26.5% lower on Day 3 (P=0.015), when maximum insulin levels were 46.4% higher (P=0.003). Glucose levels (mean [interquartile range]) were significantly lower on Day 3 for PP (168.2 [145.8] mg/dL vs. 139.4 [77.8] mg/dL; P=0.013), but not significantly so for CP (159.0 [66.1] mg/dL vs. 139.5 [57.9] mg/dL; P=0.084). Mean insulin levels were significantly higher on Day 3 for CP (195 [120] pmol/L vs. 230 [90] pmol/L; P=0.01), but not significantly so for PP (178 [106] pmol/L vs. 194 [120] pmol/L; P=0.099). There were no significant differences between the two catheter lengths. Conclusions: Postprandial glycemic excursions were lower on Day 3 of catheter wear time, but there were no differences between PPs and CPs. These findings support the proposal that catheter wear time plays an important role in insulin absorption.
Diabetes Technology & Therapeutics 05/2013; · 1.93 Impact Factor
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ABSTRACT: Endothelial integrity is maintained by local neighboring cells, but studies in the field of regenerative medicine have highlighted that circulating bone marrow-derived endothelial progenitor cells (EPCs) contribute to endothelial homeostasis in health and disease. In addition, bone-marrow derived smooth muscle precursors may be recruited to the diseased vasculature. Therefore, modulation of vascular stem/progenitor cells holds promises to tackle the development and progression of vascular disease. The dipeptidyl peptidase-4 (DPP-4) ectopeptidase cleaves several proteins, including the incretin hormones that regulate meal-induced insulin release. Another attractive DPP-4 natural substrate is the highly-conserved chemokine SDF-1α, a major regulator of stem/progenitor cell trafficking in the bone marrow and tissues. DPP-4 might also broadly affect bone marrow function, by acting on hematopoietic growth factors. Emerging data indicate that diabetes is associated with impaired bone marrow structure and function, which translates into pauperization of vascular regenerative cells and contributes to vascular disease. DPP-4 inhibition has potentials to tackle these alteration and promote vascular repair. Currently, millions of diabetic patients around the world are being treated with DPP-4 inhibitors and the study of ancillary effects is gaining an increasing interest for the possible cardiovascular benefit of these drugs beyond glucose control. As DPP-4 inhibitors show favorable safety profiles and do not cause hypoglycemia, they are attractive drugs also for non-diabetic patients and may become part of a vascular regenerative pharmacotherapy.
Atherosclerosis 04/2013; · 3.79 Impact Factor
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ABSTRACT: Diabetes triggers endothelial dysfunction, which is linked to increased risk of cardiovascular diseases. Stem and progenitors cells from the bone marrow are involved in the maintenance of vascular integrity. Diabetic patients show a dysfunction of these cells, which might represent a novel pathophysiological mechanism of vascular disease. Specifically, stem and progenitor cells fail to egress from the bone marrow (BM) due to BM pathological alterations and unresponsiveness to mobilizing stimuli. In this review, we describe impaired stem cell mobilization in diabetes as a mechanism of failed vascular repair and we provide evidence that pharmacological strategies can restore mobilization. We discuss recent advances in the knowledge of aberrant organization of the diabetic BM and its implications for impaired mobilization. Finally, we describe in detail the pharmacological exploitation of the G-CSF/DPP-4(CD26)/SDF-1α axis as a novel strategy to improve mobilization and attain vascular repair in diabetes.
Vascular Pharmacology 01/2013; · 1.99 Impact Factor
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Gian Paolo Fadini,
Mattia Albiero,
Florian Seeger,
Nicol Poncina,
Lisa Menegazzo,
Annalisa Angelini,
Chiara Castellani,
Gaetano Thiene,
Carlo Agostini,
Roberta Cappellari,
Elisa Boscaro,
Andreas Zeiher,
Stefanie Dimmeler, Angelo Avogaro
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ABSTRACT: Bone marrow (BM) derived stem and progenitor cells contribute to cardiovascular homeostasis and are affected by cardiovascular risk factors. We devised a clinical data-driven approach to test candidate stem cell mobilizing mechanisms in pre-clinical models. We found that PB and BM CD34+ cell counts were directly correlated, and that most circulating CD34+ cells were viable, non-proliferating and derived from the BM. Thus, we analyzed PB and BM CD34+ cell levels as a two-compartment model in 72 patients with or without cardiovascular disease. Self-organizing maps showed that disturbed compartmentalization of CD34+ cells was associated with aging and cardiovascular risk factors especially diabetes. High activity of DPP-4, a regulator of the mobilizing chemokine SDF-1α, was associated with altered stem cell compartmentalization. For validation of these findings, we assessed the role of DPP-4 in the BM mobilization response of diabetic rats. Diabetes differentially affected DPP-4 activity in PB and BM and impaired stem/progenitor cell mobilization after ischemia or G-CSF administration. DPP-4 activity in the BM was required for the mobilizing effect of G-CSF, while in PB it blunted ischemia-induced mobilization. Indeed, DPP-4 deficiency restored ischemia (but not G-CSF)-induced stem cell mobilization and improved vascular recovery in diabetic animals. In conclusion, the analysis of stem cell compartmentalization in humans led us to discover mechanisms of BM unresponsiveness in diabetes determined by tissue-specific DPP-4 dysregulation.
Archiv für Kreislaufforschung 01/2013; 108(1):313. · 7.35 Impact Factor
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ABSTRACT: BACKGROUND: Experimental diabetes impairs bone marrow (BM) mobilization of stem and progenitor cells involved in cardiovascular repair. We aimed to ascertain whether the presence of diabetes negatively affects the mobilization of stem cells induced by granulocyte-colony stimulation factor (G-CSF) in therapeutic trials for cardiovascular disease (CVD). METHODS: We conducted a meta-regression analysis of clinical trials published from 1997 to 2012 using G-CSF to yield BM stem cell mobilization in patients with CVD. We collected data on demographics, treatment regimen, degree of CD34+ cell mobilization, prevalence of diabetes and of other traditional risk factors. The primary aim was detection of a correlation between prevalence of DM and achieved CD34+ cell count after G-CSF treatment. RESULTS: We screened 227 articles, retrieved 96 for evaluation and retained 24 for the analysis of the primary end-point. There was a strong negative correlation between prevalence of diabetes and achieved CD34+ cell levels after G-CSF stimulation (r=-0.68; p<0.0001), while there was no correlation with other traditional risk factors. A multiple regression analysis showed that the correlation between diabetes and mobilization was independent. In 13 articles reporting pre- and post-G-CSF cell counts, the increase in CD34+ cells was also negatively correlated with prevalence of diabetes (r=-0.82; p<0.0001). CONCLUSIONS: In trials of BM stimulation with G-CSF for the treatment of CVD, the prevalence of diabetes is the major negative determinant of CD34+ cell mobilization. These data strongly support that diabetes impairs stem cell mobilization, with possible negative implications for CVD.
International journal of cardiology 11/2012; · 7.08 Impact Factor
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ABSTRACT: The aim of this study was to investigate the role of foot morphology, related with respect to diabetes and peripheral neuropathy in altering foot kinematics and plantar pressure during gait. Healthy and diabetic subjects with or without neuropathy with different foot types were analyzed. Three dimensional multisegment foot kinematics and plantar pressures were assessed on 120 feet: 40 feet (24 cavus, 20 with valgus heel and 11 with hallux valgus) in the control group, 80 feet in the diabetic (25 cavus 13 with valgus heel and 13 with hallux valgus) and the neuropathic groups (28 cavus, 24 with valgus heel and 18 with hallux valgus). Subjects were classified according to their foot morphology allowing further comparisons among the subgroups with the same foot morphology. When comparing neuropathic subjects with cavus foot, valgus heel with controls with the same foot morphology, important differences were noticed: increased dorsiflexion and peak plantar pressure on the forefoot (P<0.05), decreased contact surface on the hindfoot (P<0.03). While results indicated the important role of foot morphology in altering both kinematics and plantar pressure in diabetic subjects, diabetes appeared to further contribute in altering foot biomechanics. Surprisingly, all the diabetic subjects with normal foot arch or with valgus hallux were no more likely to display significant differences in biomechanics parameters than controls. This data could be considered a valuable support for future research on diabetic foot function, and in planning preventive interventions.
Gait & posture 11/2012; · 2.58 Impact Factor
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ABSTRACT: OBJECTIVE
Diabetes mellitus (DM) increases cardiovascular risk, at least in part, through shortage of vascular regenerative cells derived from the bone marrow (BM). In experimental models, DM causes morphological and functional BM alterations, but information on BM function in human DM is missing. Herein, we sought to assay mobilization of stem and proangiogenic cells in subjects with and without DM.RESEARCH DESIGN AND METHODS
In a prospective trial (NCT01102699), we tested BM responsiveness to 5 μg/kg human recombinant granulocyte colony-stimulating factor (hrG-CSF) in 24 individuals with DM (10 type 1 and 14 type 2) and 14 individuals without DM. Before and 24 h after hrG-CSF, we quantified circulating stem/progenitor cells and total and differential white blood cell counts. We also evaluated in vivo the proangiogenic capacity of peripheral blood mononuclear cells using the Matrigel plug assay.RESULTSIn response to hrG-CSF, levels of CD34(+) cells and other progenitor cell phenotypes increased in subjects without DM. Patients with DM had significantly impaired mobilization of CD34(+), CD133(+), and CD34(+)CD133(+) hematopoietic stem cells and CD133(+)KDR(+) endothelial progenitors, independently of potential confounders. The in vivo angiogenic capacity of peripheral blood mononuclear cells significantly increased after hrG-CSF in control subjects without DM, but not in patients with DM. DM was also associated with inability to upregulate CD26/DPP-4 on CD34(+) cells, which is required for the mobilizing effect of granulocyte colony-stimulating factor.CONCLUSIONS
Stem and proangiogenic cell mobilization in response to hrG-CSF is impaired in DM, possibly because of maladaptive CD26/DPP-4 regulation. These alterations may hamper tissue repair and favor the development of cardiovascular complications.
Diabetes care 10/2012; · 8.09 Impact Factor
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Claudio Cobelli,
Eric Renard,
Boris P Kovatchev,
Patrick Keith-Hynes,
Najib Ben Brahim,
Jérôme Place,
Simone Del Favero,
Marc Breton,
Anne Farret,
Daniela Bruttomesso,
Eyal Dassau,
Howard Zisser,
Francis J Doyle,
Stephen D Patek, Angelo Avogaro
Diabetes care 09/2012; 35(9):e65-7. · 8.09 Impact Factor
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Marc Breton,
Anne Farret,
Daniela Bruttomesso,
Stacey Anderson,
Lalo Magni,
Stephen Patek,
Chiara Dalla Man,
Jerome Place,
Susan Demartini,
Simone Del Favero,
Chiara Toffanin,
Colleen Hughes-Karvetski,
Eyal Dassau,
Howard Zisser,
Francis J Doyle,
Giuseppe De Nicolao, Angelo Avogaro,
Claudio Cobelli,
Eric Renard,
Boris Kovatchev
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ABSTRACT: Integrated closed-loop control (CLC), combining continuous glucose monitoring (CGM) with insulin pump (continuous subcutaneous insulin infusion [CSII]), known as artificial pancreas, can help optimize glycemic control in diabetes. We present a fundamental modular concept for CLC design, illustrated by clinical studies involving 11 adolescents and 27 adults at the Universities of Virginia, Padova, and Montpellier. We tested two modular CLC constructs: standard control to range (sCTR), designed to augment pump plus CGM by preventing extreme glucose excursions; and enhanced control to range (eCTR), designed to truly optimize control within near normoglycemia of 3.9-10 mmol/L. The CLC system was fully integrated using automated data transfer CGM→algorithm→CSII. All studies used randomized crossover design comparing CSII versus CLC during identical 22-h hospitalizations including meals, overnight rest, and 30-min exercise. sCTR increased significantly the time in near normoglycemia from 61 to 74%, simultaneously reducing hypoglycemia 2.7-fold. eCTR improved mean blood glucose from 7.73 to 6.68 mmol/L without increasing hypoglycemia, achieved 97% in near normoglycemia and 77% in tight glycemic control, and reduced variability overnight. In conclusion, sCTR and eCTR represent sequential steps toward automated CLC, preventing extremes (sCTR) and further optimizing control (eCTR). This approach inspires compelling new concepts: modular assembly, sequential deployment, testing, and clinical acceptance of custom-built CLC systems tailored to individual patient needs.
Diabetes 06/2012; 61(9):2230-7. · 8.29 Impact Factor
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ABSTRACT: The metabolic syndrome (MS) is characterized by chronic inflammation. We aimed to determine the association of white blood cell (WBC) count with prevalence and development of the MS and its components in the general population. A cohort of 1,329 subjects from the local working population aged 41.3 ± 7.5 years and recruited since 2000-2008 was followed up for 4.0 ± 1.2 years. WBC count and MS components were determined at baseline and follow-up. To determine whether WBC predicted incident MS, we used a logistic regression analysis adjusted for demographics, baseline variables that define MS components, smoke, medications, and follow-up duration. Cross-sectionally in the whole population, WBC count increased in parallel with the number of MS components in the same individual, and the presence of each component was associated with higher WBC count. Baseline WBC count was significantly higher in subjects with prevalent MS. Among subjects without MS at baseline, those who developed MS had significantly higher WBC than those who did not develop MS at follow-up. Development of each MS component was associated with increased WBC count. WBC count remained significantly associated with MS development after correction for several potential confounders (OR for 1 SD increase in WBC 1.26; 95 % CI 1.01-1.58). In conclusion, elevated WBC is intimately linked to the prevalence and future development of the MS in a young population of working subjects.
Acta Diabetologica 05/2012; · 2.78 Impact Factor
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ABSTRACT: The Zone diet (ZD) is centreed primarily on protein intake. Previous findings have assessed the role of ZD on glucose metabolism,
but the outcomes have been conflicting. So far, there is no clear evidence of the effects of ZD on insulin response. Furthermore,
the effect of ZD on insulin sensitivity has never been clearly determined yet. Our aim was to evaluate in healthy subjects
how ZD acts on body composition, lipid profile and overall on insulin sensitivity and secretion in dynamic conditions. We
also compared ZD effects with those of the Mediterranean diet (MD). Twelve volunteers were studied. Subjects were randomized
either to MD or to ZD for 8weeks. A wash-out period followed. Afterwards, subjects were crossed over to the other diet for
other 8weeks. At any end-point subjects underwent standard 75g oral glucose tolerance test for measurements of glucose,
insulin, C-peptide, proinsulin and glucagon. Lipids and free fatty acids were determined at fasting. Insulin sensitivity was
assessed by the oral glucose insulin sensitivity index. Insulin secretion was determined by mathematical modelling of insulin
and C-peptide data. No significant differences were observed following both diets in body weight, fat mass and plasma glucose,
insulin, C-peptide, proinsulin and glucagon levels. Similarly, insulin sensitivity and secretion were not different in both
absolute values and changes from baseline. Decrease in triglyceride and increase in HDL–cholesterol levels were observed after
ZD compared with MD. Thus, it was determined that intake of high-protein diet for 2 months does not modify insulin action
and secretion, but improves lipid profile.
KeywordsDietary carbohydrates-Dietary proteins-Insulin-Cholesterol-Humans
Mediterranean Journal of Nutrition and Metabolism 04/2012; 3(3):233-237.
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ABSTRACT: Diabetes mellitus is associated with an increased risk of cardiovascular disease due to its negative impact on the vascular endothelium. The damaged endothelium is repaired by resident cells also through the contribution of a population of circulating cells derived from bone marrow. These cells, termed endothelial progenitor cells (EPCs) are involved in maintaining endothelial homeostasis and contributes to the formation of new blood vessels with a process called postnatal vasculogenesis. The mechanisms whereby these cells allow for protection of the cardiovascular system are still unclear; nevertheless, consistent evidences have shown that impairment and reduction of EPCs are hallmark features of type 1 and type 2 diabetes. Therefore, EPC alterations might have a pathogenic role in diabetic complications, thus becoming a potential therapeutic target. In this review, EPC alterations will be examined in the context of macrovascular and microvascular complications of diabetes, highlighting their roles and functions in the progression of the disease.
BioFactors 04/2012; 38(3):194-202. · 4.93 Impact Factor
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ABSTRACT: The fundamental cause of lower-extremity complications in diabetes is chronic hyperglycemia leading to diabetic foot ulcer pathology. While the relationship between abnormal plantar pressure distribution and plantar ulcers has been widely investigated, little is known about the role of shear stress. Moreover, the mutual relationship among plantar pressure, shear stress, and abnormal kinematics in the etiology of diabetic foot has not been established. This lack of knowledge is determined by the lack of commercially available instruments which allow such a complex analysis. This study aims to develop a method for the simultaneous assessment of kinematics, kinetics, and plantar pressure on foot subareas of diabetic subjects by means of combining three commercial systems. Data were collected during gait on 24 patients (12 controls and 12 diabetic neuropathics) with a motion capture system synchronized with two force plates and two baropodometric systems. A four segment three-dimensional foot kinematics model was adopted for the subsegment angles estimation together with a three segment model for the plantar sub-area definition during gait. The neuropathic group exhibited significantly excessive plantar pressure, ground reaction forces on each direction, and a reduced loading surface on the midfoot subsegment (p<0.04). Furthermore the same subsegment displayed excessive dorsiflexion, external rotation, and eversion (p<0.05). Initial results showed that this methodology may enable a more appropriate characterization of patients at risk of foot ulcerations, and help planning prevention programs.
Gait & posture 03/2012; 36(1):20-6. · 2.58 Impact Factor
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ABSTRACT: Ischemic recruitment of endothelial progenitor cells (EPCs) in involved in compensatory angiogenic in animal models, but this still needs to be substantiated in humans. We enrolled 12 patients, who underwent surgical correction of abdominal aortic aneurysm without atherosclerosis of leg arteries (n = 4) or lower limb atherosclerosis obliterans (AO; n = 8). We measured VEGF, SDF-1, lactate and CD34+ KDR+ EPCs in the arterial and venous circulation of lower limbs. We found that, irrespectively of AO stage and lactate production, there was no consistent arterio-venous gradient of EPC, VEGF and SDF-1. Notably, in 4/8 patients, EPCs were more abundant in the vein than in the artery. EPC gradient was directly correlated with VEGF gradient and inversely correlated with SDF-1 gradient. In conclusion, we failed to show any consistent gradient of EPCs across ischemic limbs in relation to severity of atherosclerosis obliterans, but we speculatively suggest that a bidirectional traffic of EPCs in and out the ischemic tissue might be regulated by VEGF and SDF-1.
Clinical hemorheology and microcirculation 01/2012; 50(4):293-300. · 3.40 Impact Factor
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ABSTRACT: Diabetes mellitus (DM) is a worldwide growing disease and represents a huge social and healthcare problem owing to the burden of its complications. Micro- and macrovascular diabetic complications arise from excess damage through well-known biochemical pathways. Interestingly, microangiopathy hits the bone marrow (BM) microenvironment with features similar to retinopathy, nephropathy and neuropathy. The BM represents a reservoir of progenitor cells for multiple lineages, not limited to the hematopoietic system and including endothelial cells, smooth muscle cells, cardiomyocytes, and osteogenic cells. All these multiple progenitor cell lineages are profoundly altered in the setting of diabetes in humans and animal models. Reduction of endothelial progenitor cells (EPCs) along with excess smooth muscle progenitor (SMP) and osteoprogenitor cells creates an imbalance that promote the development of micro- and macroangiopathy. Finally, an excess generation of BM-derived fusogenic cells has been found to contribute to diabetic complications in animal models. Taken together, a growing amount of literature attributes to circulating progenitor cells a multi-faceted role in the pathophysiology of DM, setting a novel scenario that puts BM and the blood at the centre of the stage.
Experimental Diabetes Research 01/2012; 2012:742976. · 1.20 Impact Factor
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ABSTRACT: Diabetes mellitus (DM) alters circulating progenitor cells relevant for the pathophysiology of coronary artery disease (CAD). While endothelial progenitor cells (EPCs) are reduced, there is no data on procalcific polarization of circulating progenitors, which may contribute to vascular calcification in these patients. In a cohort of 107 subjects with and without DM and CAD, we analyzed the pro-calcific versus endothelial differentiation status of circulating CD34+ progenitor cells. Endothelial commitment was determined by expression of VEGFR-2 (KDR) and pro-calcific polarization by expression of osteocalcin (OC) and bone alkaline phosphatase (BAP). We found that DM patients had significantly higher expression of OC and BAP on circulating CD34+ cells than control subjects, especially in the presence of CAD. In patients with DM and CAD, the ratio of OC/KDR, BAP/KDR, and OC+BAP/KDR was about 3-fold increased than in other groups. EPCs cultured from DM patients with CAD occasionally formed structures highly suggestive of calcified nodules, and the expression of osteogenic markers by EPCs from control subjects was significantly increased in response to the toll-like receptor agonist LPS. In conclusion, circulating progenitor cells of diabetic patients show a phenotypic drift toward a pro-calcific phenotype that may be driven by inflammatory signals.
Experimental Diabetes Research 01/2012; 2012:921685. · 1.20 Impact Factor
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ABSTRACT: Chronic diabetic complications result from an imbalance between vascular damage and regeneration. Several circulating lineage-committed progenitor cells have been implicated, but no data are available on pericyte progenitor cells (PPCs). Based on the evidence that PPCs increase in cancer patients after chemotherapy, we explored whether circulating PPC levels are affected by glucose control in type 2 diabetic patients, in relation to the presence of chronic complications. We enumerated peripheral blood PPCs as Syto16+CD45-CD31-CD140b+ events by flow cytometry at baseline and after 3 and 6 months of glucose control by means of add-on basal insulin therapy on top of oral agents in 38 poorly controlled type 2 diabetic patients. We found that, in patients with microangiopathy (n = 23), the level of circulating PPCs increased about 2 fold after 3 months and then returned to baseline at 6 months. In patients without microangiopathy (control group, n = 15), PPCs remained fairly stable during the whole study period. No relationship was found between change in PPCs and macroangiopathy (either peripheral, coronary, or cerebrovascular). We conclude that glucose control transiently mobilizes PPCs diabetic patients with microangiopathy. Increase in PPCs may represent a vasoregenerative event or may be a consequence of ameliorated glucose control on microvascular lesions.
Experimental Diabetes Research 01/2012; 2012:274363. · 1.20 Impact Factor
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Stefano Bonvini,
Mattia Albiero,
Luca Ferretto,
Annalisa Angelini,
Piero Battocchio,
Marny Fedrigo,
Michele Piazza,
Gaetano Thiene, Angelo Avogaro,
Gian Paolo Fadini,
Franco Grego
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ABSTRACT: The peritoneum has the same developmental origin as blood vessels, is highly reactive and poorly thrombogenic. We hypothesize that parietal peritoneum can sustain development and regeneration of new vessels.
The study comprised two experimental approaches. First, to test surgical feasibility and efficacy of the peritoneal vascular autograft, we set up an autologous transplantation procedure in pigs, where a tubularized parietal peritoneal graft was covered with a metal mesh and anastomosed end-to-end in the infrarenal aorta. Second, to dissect the contribution of graft vs host cells to the newly developed vessel wall, we performed human-to-rat peritoneal patch grafting in the abdominal aorta and examined the origin of endothelial and smooth muscle cells. In pig experiments, the graft remodeled to an apparently normal blood vessel, without thrombosis. Histology confirmed arterialization of the graft with complete endothelial coverage and neointimal hyperplasia in the absence of erosion, inflammation or thrombosis. In rats, immunostaining for human mitochondri revealed that endothelial cells and smooth muscle cells rarely were of human origin. Remodeling of the graft was mainly attributable to local cells with no clear evidence of c-kit+ endothelial progenitor cells or c-kit+ resident perivascular progenitor cells.
The parietal peritoneum can be feasibly used as a scaffold to sustain the regeneration of blood vessels, which appears to occur through the contribution of host-derived resident mature cells.
PLoS ONE 01/2012; 7(3):e33557. · 4.09 Impact Factor
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ABSTRACT: Nutrient balance in the human body is maintained through systemic signaling between different cells and tissues. Breaking down this circuitry to its most basic elements and reconstructing the metabolic network in-vitro provides a systematic method to gain a better understanding of how cross-talk between the organs contributes to the whole body metabolic profile and of the specific role of each different cell type. To this end, a 3-way connected culture of hepatocytes, adipose tissue and endothelial cells representing a simplified model of energetic substrate metabolism in the visceral region was developed. The 3-way culture was shown to maintain glucose and fatty acid homeostasis in-vitro. Subsequently it was challenged with insulin and high glucose concentrations to simulate hyperglycaemia. The aim was to study the capacity of the 3-way culture to maintain or restore normal circulating glucose concentrations in response to insulin and to investigate the effects these conditions on other metabolites involved in glucose and lipid metabolism. The results show that the system's metabolic profile changes dramatically in the presence of high concentrations of glucose, and that these changes are modulated by the presence of insulin. Furthermore, we observed an increase in E-selectin levels in hyperglycaemic conditions and increased IL-6 concentrations in insulin-free-hyperglycaemic conditions, indicating, respectively, endothelial injury and proinflammatory stress in the challenged 3-way system.
PLoS ONE 01/2012; 7(4):e34704. · 4.09 Impact Factor
