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BACKGROUND: While rapid healing of diabetic foot ulcers (DFUs) is highly desirable to avoid infections, amputations and life-threatening complications, DFUs often respond poorly to standard treatment. GMP-manufactured skin-derived ABCB5+ mesenchymal stem cells (MSCs) might provide a new adjunctive DFU treatment, based on their remarkable skin wound homing and engraftment potential, their ability to adaptively respond to inflammatory signals, and their wound healing-promoting efficacy in mouse wound models and human chronic venous ulcers. METHODS: The angiogenic potential of ABCB5+ MSCs was characterized with respect to angiogenic factor expression at the mRNA and protein level, in vitro endothelial trans-differentiation and tube formation potential, and perfusion-restoring capacity in a mouse hindlimb ischemia model. Finally, the efficacy and safety of ABCB5+ MSCs for topical adjunctive treatment of chronic, standard therapy-refractory, neuropathic plantar DFUs were assessed in an open-label single-arm clinical trial. RESULTS: Hypoxic incubation of ABCB5+ MSCs led to posttranslational stabilization of the hypoxia-inducible transcription factor 1α (HIF-1α) and upregulation of HIF-1α mRNA levels. HIF-1α pathway activation was accompanied by upregulation of vascular endothelial growth factor (VEGF) transcription and increase in VEGF protein secretion. Upon culture in growth factor-supplemented medium, ABCB5+ MSCs expressed the endothelial-lineage marker CD31, and after seeding on gel matrix, ABCB5+ MSCs demonstrated formation of capillary-like structures comparable with human umbilical vein endothelial cells. Intramuscularly injected ABCB5+ MSCs to mice with surgically induced hindlimb ischemia accelerated perfusion recovery as measured by laser Doppler blood perfusion imaging and enhanced capillary proliferation and vascularization in the ischemic muscles. Adjunctive topical application of ABCB5+ MSCs onto therapy-refractory DFUs elicited median wound surface area reductions from baseline of 59% (full analysis set, n = 23), 64% (per-protocol set, n = 20) and 67% (subgroup of responders, n = 17) at week 12, while no treatment-related adverse events were observed. CONCLUSIONS: The present observations identify GMP-manufactured ABCB5+ dermal MSCs as a potential, safe candidate for adjunctive therapy of otherwise incurable DFUs and justify the conduct of a larger, randomized controlled trial to validate the clinical efficacy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03267784, Registered 30 August 2017, https://clinicaltrials.gov/ct2/show/NCT03267784.
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Subfamilia B de Transportador de Casetes de Unión a ATP , Pie Diabético , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Neovascularización Fisiológica , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Animales , Dermis/citología , Dermis/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Pie Diabético/genética , Pie Diabético/metabolismo , Pie Diabético/patología , Pie Diabético/terapia , Humanos , Isquemia/metabolismo , Isquemia/terapia , Células Madre Mesenquimatosas/metabolismo , Ratones , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Fisiológica/fisiología , ARN Mensajero/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cicatrización de Heridas/genética , Cicatrización de Heridas/fisiologíaRESUMEN
BACKGROUND: The efficacy/safety of device-supported versus routine titration with Gla-300 in type 2 diabetes (T2DM) was evaluated. METHOD: AUTOMATIX was a 16-week, randomized, open-label, parallel-group, multicenter, noninferiority trial in insulin-treated or insulin-naïve people with T2DM. The fasting self-monitored plasma glucose (FSMPG) target was 90-130 mg/dL (5.0-7.2 mmol/L). Primary endpoint: proportion of participants achieving target FSMPG at week 16 without severe hypoglycemia. Secondary endpoints included: proportion reaching FSMPG target without confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycemia; time to first achieve FSMPG target; mean FSMPG and HbA1c change (baseline to week 16). Safety endpoints included hypoglycemia and adverse events. Patient-reported outcomes (PROs) were also assessed. RESULTS: Participants were randomized to device-supported (n = 75) or routine titration (n = 76); 17 participants in the device-supported group discontinued device use. Noninferiority was achieved for the primary endpoint (device-supported: 45.9%, routine: 36.8%; weighted difference: 9.04 [95% CI: -6.75, 24.83]), but not superiority (P = .262). The proportion reaching FSMPG target range without confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycemia was 34.3% vs 14.5%, respectively. The time at which 50% of the participants achieved the FSMPG target was less in the device-supported than routine titration arm (10 vs 13 weeks). Least squares mean HbA1c reduction, safety profiles, and PROs were similar in both arms. Mean "ease of use" score for the device, assessed by healthcare professionals and participants on a scale of 1-7, was ≥6. CONCLUSIONS: Device-supported self-titration had a good safety/efficacy profile, and was noninferior to routine titration and well accepted by diabetes specialists and patients.
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Automonitorización de la Glucosa Sanguínea/métodos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina Glargina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Glucemia , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In the original publication, the text in Table 2 stated 'Hypersensitivity to the active substance, to Ferinject, or to any of its excipients'.
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OBJECTIVE: This 24-week, double-blinded, phase 3 clinical trial (DEPICT-2; ClinicalTrials.gov, NCT02460978) evaluated efficacy and safety of dapagliflozin as adjunct therapy to adjustable insulin in patients with inadequately controlled type 1 diabetes (HbA1c 7.5-10.5%). RESEARCH DESIGN AND METHODS: Patients were randomized 1:1:1 to dapagliflozin 5 mg (n = 271), dapagliflozin 10 mg (n = 270), or placebo (n = 272) plus insulin. Insulin dose was adjusted by investigators according to self-monitored glucose readings, local guidance, and individual circumstances. RESULTS: Baseline characteristics were balanced between treatment groups. At week 24, dapagliflozin significantly decreased HbA1c (primary outcome; difference vs. placebo: dapagliflozin 5 mg -0.37% [95% CI -0.49, -0.26], dapagliflozin 10 mg -0.42% [-0.53, -0.30]), total daily insulin dose (-10.78% [-13.73, -7.72] and -11.08% [-14.04, -8.02], respectively), and body weight (-3.21% [-3.96, -2.45] and -3.74% [-4.49, -2.99], respectively) (P < 0.0001 for all). Mean interstitial glucose, amplitude of glucose excursion, and percent of readings within target glycemic range (>70 to ≤180 mg/dL) versus placebo were significantly improved. More patients receiving dapagliflozin achieved a reduction in HbA1c ≥0.5% without severe hypoglycemia compared with placebo. Adverse events were reported for 72.7%, 67.0%, and 63.2% of patients receiving dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo, respectively. Hypoglycemia, including severe hypoglycemia, was balanced between groups. There were more adjudicated definite diabetic ketoacidosis (DKA) events with dapagliflozin: 2.6%, 2.2%, and 0% for dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo, respectively. CONCLUSIONS: Dapagliflozin as adjunct therapy to adjustable insulin in patients with type 1 diabetes was well tolerated and improved glycemic control with no increase in hypoglycemia versus placebo but with more DKA events.
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Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Adulto , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Peso Corporal , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/epidemiología , Cetoacidosis Diabética/inducido químicamente , Cetoacidosis Diabética/epidemiología , Método Doble Ciego , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
INTRODUCTION: HbA1c is the gold standard for glycemic control in pre-diabetes and diabetes. However, its validity has been questioned, especially in the presence of imbalanced iron homeostasis. The CLEVER trial aims to evaluate the relationship between iron deficiency and HbA1c (a biomarker for the diagnosis and therapeutic monitoring of type 2 diabetes) in a randomized, placebo-controlled, multicenter clinical trial. METHODS: The CLEVER (intravenous ferric CarboxymaLtosE for improVement of mEtabolic parameters in type 2 diabetes patients with iRon deficiency) trial is a randomized, single-blind, proof-of-concept study with two treatment arms. 140 men and women diagnosed with type 2 diabetes and iron deficiency will receive either placebo or ferric carboxymaltose (500 or 1000 mg) as intravenous infusions. The primary outcome measure is the change in HbA1c level between baseline and after 12 weeks of treatment. Secondary endpoints include change of iron status and metabolic markers as well as treatment safety and tolerability. Furthermore, the potential clinical improvement in quality of life and the reliability of HbA1c measurement in patients with type 2 diabetes and iron deficiency will be investigated. RESULTS: Both excessive iron and iron deficiency are associated with metabolic disorders; excessive iron is a risk factor for the development of diabetes, whereas iron deficiency is associated with obesity and insulin resistance. It has been suggested that iron increases insulin secretion in pancreatic beta-cells. CLEVER is the first study to investigate the hypothesis that intravenous substitution with ferric carboxymaltose reduces HbA1c levels in patients with type 2 diabetes and iron deficiency, thereby improving metabolic status and quality of life. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01513369). FUNDING: GWT-TUD GmbH acts as sponsor of the clinical trial. Financial support is provided by Vifor Pharma.
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BACKGROUND: A lower incidence of cardiovascular events has been reported in type 2 diabetes patients treated with insulin analogs (IAs). Corresponding data on people affected by type 1 diabetes are not available yet. METHODOLOGY: We investigated demographic and clinical data from 509 type 1 diabetics, who were treated in an outpatient clinic from 2006 to 2012. Multiple logistic regression was used to investigate the relationship between the type of insulin treatment and the prevalence of cardiovascular (CV) complications, that is, presence of coronary heart, cerebrovascular and peripheral arterial diseases, adjusting for potential confounders. RESULTS: Results from multiple logistic regression revealed that patients with impaired renal function [estimated glomerular filtration rate (eGFR) < 90 ml/min] show lower CV complication rates when treated with IAs (25%) compared with patients treated with human insulin (HI; 28%) and HI/IA (38%, p = 0.06). CV complication rates in the complete patient collective amounted to 17% (IA), 21% (HI) and 21% (HI/IA, p = 0.08). Examination of CV complications according to the type of IA revealed the lowest complication rates in type 1 diabetics treated with insulin lispro (5.9%) and glargine (16%). However, complication rate differences among insulin treatments did not reach statistical significance. CONCLUSION: The present cross-sectional study shows a borderline significantly lower CV morbidity in people with type 1 diabetes and impaired renal function when treated with IA compared with HI treatment after adjustment for multiple potential confounders [odds ratio (OR) = 0.78, which translates into a 22% lower complication rate]. Validation of these preliminary findings in confirmatory, prospective studies may have important clinical implications.
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OBJECTIVES: The influence of type of insulin treatment - insulin analogs versus human insulin - on the development of diabetes related vascular complications has been sparsely investigated. We examine here possible differences regarding kidney function and hemoglobin levels. METHODS: Multiple linear regression was used to investigate the relationship between the following characteristics measured in 509 type 1 diabetic patients who were recruited in an outpatient practice: current clinical status and treatment modalities, type of injected insulin and the routine laboratory parameters hemoglobin, HbA1c, serum creatinine, eGFR, hs CRP and urinary albumin/creatinine ratio. RESULTS: Compared with human insulin, multiple regression analysis taking into account possible confounders revealed that treatment with insulin analogs was associated with increased eGFR (+7.1 ml/min; P=0.0002), lower urinary albumin/creatinine ratio (ratio logarithm -0.4; P=0.003) and higher hemoglobin concentration (+0.31 g/dl; P=0.04). Stratification by type of insulin showed the best renal status for treatment with insulins Glargine and Lispro. Differences were consistent both for patients with normal (eGFR â 90 ml/min) and with an impaired (eGFR â 90 ml/min) kidney function. CONCLUSIONS: Present results suggest that treatment of type 1 diabetic patients with normal and impaired renal function with insulin analogs, especially Glargine and Lispro, is associated with better kidney function, lower urinary albumin/creatinine ratio and lower hemoglobin concentration compared to therapy with human insulin. If confirmed by other studies, treatment with insulin analogs may be a further possibility in delaying progression of nephropathy and in preventing early hemoglobin decline.
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BACKGROUND: 1,5-Anhydroglucitol (1,5-AG) is a new blood glucose control marker reflecting temporary glucose elevations. However, 1,5-AG is of limited value in patients with advanced renal insufficiency. The aim of the present study was to assess the correlation between 1,5-AG levels and renal function in patients with earlier stages of nephropathy compared with another two markers of diabetes control, namely HbA1c and glycated albumin (GA). METHODS: The following parameters were measured in 377 patients with type 2 diabetes: HbA1c, serum concentrations of 1,5-AG, GA and creatinine, hemoglobin, urinary albumin/creatinine ratio, and urinary excretion of α1 -microglobulin (A1M). Estimated glomerular filtration rate (eGFR) was calculated according to the Cockgroft-Gault formula. RESULTS: There was a negative correlation between 1,5-AG and renal function (r = -0.18; P < 0.001). Concentrations of 1,5-AG were, on average, 27.2% lower in patients with glomerular hyperfiltration (eGFR >120 mL/min) compared with patients with moderate renal impairment (eGFR 30-59 mL/min; P = 0.016). In contrast, HbA1c, GA levels and urinary A1M excretion did not differ between the two patient groups. The mean age of patients with eGFR 30-59 mL/min was substantially higher than that of patients with glomerular hyperfiltration (P < 0.001). Thus, an age-related change in the renal glucose threshold could be the reason for the observed correlation between 1,5-AG and renal function. CONCLUSIONS: In clinical practice, age and renal function must be taken into consideration when interpreting 1,5-AG levels, even in the absence of advanced renal impairment.
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Desoxiglucosa/sangre , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/metabolismo , Insuficiencia Renal Crónica/sangre , Albúmina Sérica/metabolismo , Anciano , Albuminuria/orina , alfa-Globulinas/orina , Biomarcadores/sangre , Biomarcadores/orina , Creatinina/sangre , Creatinina/orina , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/fisiopatología , Femenino , Tasa de Filtración Glomerular , Productos Finales de Glicación Avanzada , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Índice de Severidad de la Enfermedad , Albúmina Sérica GlicadaRESUMEN
We investigated the analytical accuracy of 27 glucose monitoring systems (GMS) in a clinical setting, using the new ISO accuracy limits. In addition to measuring accuracy at blood glucose (BG) levels < 100 mg/dl and > 100 mg/dl, we also analyzed devices performance with respect to these criteria at 5 specific BG level ranges, making it possible to further differentiate between devices with regard to overall performance. Carbohydrate meals and insulin injections were used to induce an increase or decrease in BG levels in 37 insulin-dependent patients. Capillary blood samples were collected at 10-minute intervals, and BG levels determined simultaneously using GMS and a laboratory-based method. Results obtained via both methods were analyzed according to the new ISO criteria. Only 12 of 27 devices tested met overall requirements of the new ISO accuracy limits. When accuracy was assessed at BG levels < 100 mg/dl and > 100 mg/dl, criteria were met by 14 and 13 devices, respectively. A more detailed analysis involving 5 different BG level ranges revealed that 13 (48.1%) devices met the required criteria at BG levels between 50 and 150 mg/dl, whereas 19 (70.3%) met these criteria at BG levels above 250 mg/dl. The overall frequency of outliers was low. The assessment of analytical accuracy of GMS at a number of BG level ranges made it possible to further differentiate between devices with regard to overall performance, a process that is of particular importance given the user-centered nature of the devices' intended use.
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Automonitorización de la Glucosa Sanguínea/instrumentación , Glucemia/metabolismo , Diabetes Mellitus/diagnóstico , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Automonitorización de la Glucosa Sanguínea/normas , Diabetes Mellitus/sangre , Diabetes Mellitus/tratamiento farmacológico , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/metabolismo , Diseño de Equipo , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Ensayo de Materiales , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The accuracy of glucose meters (GMs) for self-monitoring of blood glucose (BG) is essential for preventing insulin dosage errors in insulin injecting diabetic patients. We evaluated the accuracy of 19 commercially available GMs in a clinical setting applying the new planned ISO criteria. METHODS: Capillary blood was taken at 10-minute intervals in insulin dependent patients during induction of a BG increase and decrease by administration of a standardized carbohydrate rich meal and/or injection of an appropriate dosage of insulin under medical supervision. BG was measured simultaneously by GMs and a laboratory method (Hitado Super GL). The GM results were compared with a laboratory reference method according to the current ISO criteria (ISO 15197:2003) and the proposed (more stringent) criteria. RESULTS: Evaluating GM results according to the current ISO criteria, all GMs reached the minimum acceptable system accuracy criteria. Analysing GM results according to the more stringent planned ISO standard criteria, only 8 of 19 GMs reached the minimum acceptable accuracy criteria, i.e. > or = 95% of the individual glucose results fell within +/- 15 mg/dL of the results of the reference value at glucose concentrations < 100 mg/dL and within +/- 15% at glucose concentrations > or = 100 mg/dL. When results obtained in BG ranges < and > or = 100 mg/dL were separately analysed, readings of 10 and 8 GMs, respectively, fell in the area of acceptable accuracy. CONCLUSIONS: The study shows that more than half of the tested GMs would fail the proposed tighter ISO criteria. Most GMs reveal similar accuracy in BG measurement when compared at lower and higher BG ranges.
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Automonitorización de la Glucosa Sanguínea/métodos , Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Humanos , Estándares de ReferenciaRESUMEN
OBJECTIVES: In diabetic nephropathy the decline of renal function causes modifications of the insulin and carbohydrate metabolism resulting in changed insulin requirements. The aim of the present study was to identify potential differences in the requirements of human insulin and various insulin analogues in patients with type 1 diabetes mellitus and renal dysfunction. METHODS: The insulin requirements of 346 patients with type 1 diabetes mellitus under everyday life circumstances were assessed in an observational study. Simultaneously, laboratory parameters were measured and the estimated glomerular filtration rate (eGFR) was calculated using the formula by Cockcroft-Gault. Medical history and concomitant medication were recorded. The insulin requirements of long- and short-acting insulin were tested for a relationship with the eGFR and laboratory parameters. RESULTS: The dosage of long-acting human insulin did not show any relation to eGFR. In contrast, a strong positive relation between dosage and renal function was found for insulin glargine and insulin detemir. After classification according to renal function, the insulin dosage at eGFR less than 60 ml/min was 29.7% lower in glargine-treated and 27.3% lower in detemir-treated patients compared with eGFR greater than 90 ml/min. Considering the whole range of eGFR, short-acting human insulin did not show a relation with renal function. Only after classification according to renal function was a dose reduction found for human insulin at eGFR less than 60 ml/min. In contrast, requirements of insulin lispro were significantly related to eGFR over the whole range of eGFR. At eGFR less than 60 ml/min the insulin dosage was 32.6% lower than at eGFR greater than 90 ml/min. The requirements of insulin aspart did not show any association with the eGFR. CONCLUSIONS: Patients with type 1 diabetes mellitus show different insulin requirements according to the renal function depending on the applied insulin. This finding is essential for the adjustment of insulin therapy in patients with diabetic nephropathy to achieve balanced glycemic control. To determine the underlying mechanisms, further studies on the pharmacokinetics and pharmacodynamics of the different insulins in patients with diabetic nephropathy are needed.
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BACKGROUND: This article describes a new fiber-coupled, percutaneous fluorescent continuous glucose monitoring (CGM) system that has shown 14 days of functionality in a human clinical trial. METHOD: The new optical CGM system (FiberSense) consists of a transdermal polymer optical fiber containing a biochemical glucose sensor and a small fluorescence photometer optically coupled to the fiber. The glucose-sensitive optical fiber was implanted in abdominal and upper-arm subcutaneous tissue of six diabetes patients and remained there for up to 14 days. The performance of the system was monitored during six visits to the study center during the trial. Blood glucose changes were induced by oral carbohydrate intake and insulin injections, and capillary blood glucose samples were obtained from the finger tip. The data were analyzed using linear regression and the consensus error grid analysis. RESULTS: The FiberSense worn at the upper arm exhibited excellent results during 14 wearing days, with an overall mean absolute relative difference (MARD) of 8.3% and 94.6% of the data in zone A of the consensus error grid. At the abdominal application site, FiberSense resulted in a MARD of 11.4 %, with 93.8% of the data in zone A. CONCLUSIONS: The FiberSense CGM system provided consistent, reliable measurements of subcutaneous glucose levels in human clinical trial patients with diabetes for up to 14 days.
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Técnicas Biosensibles/instrumentación , Automonitorización de la Glucosa Sanguínea/instrumentación , Diabetes Mellitus/sangre , Monitoreo Ambulatorio/instrumentación , Técnicas Biosensibles/métodos , Glucemia/análisis , Femenino , Transferencia Resonante de Energía de Fluorescencia , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio/métodosRESUMEN
BACKGROUND: To evaluate the feasibility of an implantable subconjunctival glucose monitoring system (SGMS) for long-term glucose monitoring, we investigated the in vivo performance of the system. METHOD: The SGMS consists of an implantable ocular mini implant (OMI) and a handheld fluorescence photometer. A clinical study was performed on 47 diabetes patients split into two cohorts. Two different types of OMI were used, with and without a biocompatible surface coating. Duration of the study was 1 year. Correlation between capillary blood glucose and SGMS-derived interstitial fluid glucose was investigated during the first 6 months of the study. RESULTS: Both OMI types were tolerated well in the eyes of the patients. At the beginning of the study, the SGMS of both cohorts revealed a high accuracy with mean absolute relative difference (MARD) values of 7-12%. The performance of the uncoated OMIs deteriorated within 3 months of wearing time, exhibiting a MARD value of 20%. The performance of the surface-coated OMIs was preserved longer. Glucose correlation measurement with reasonable results (MARD of 14%) could be performed for up to 6 months of wear. CONCLUSIONS: The biocompatible surface coating on the OMIs enabled a longer duration of action of up to 6 months compared with 3 months for uncoated implants in a clinical trial.
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Técnicas Biosensibles/instrumentación , Automonitorización de la Glucosa Sanguínea/instrumentación , Glucemia/análisis , Conjuntiva/cirugía , Diabetes Mellitus/sangre , Técnicas Biosensibles/métodos , Automonitorización de la Glucosa Sanguínea/métodos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Factores de TiempoRESUMEN
BACKGROUND: A new biosensor has been developed by EyeSense (Großostheim, Germany) that is placed into the conjunctiva of one eye to measure the glucose concentration of the surrounding tissue in a non-invasive manner. In the present study we investigated the correlation between glucose concentrations measured by the EyeSense implant and those determined by finger prick testing, as well as the tolerability and safety of the implant over a 16-week period. METHODS: The study was performed in 28 diabetic patients. The biosensor was inserted under local anesthesia and sterile conditions. Correlations between capillary glucose measured by laboratory methods and interstitial glucose determined by the biosensor were investigated by inducing increases and decreases in glucose values between 60 and 300 mg/dL. RESULTS: Most patients experienced a mild subconjunctival hemorrhage postoperatively. Except for the minor sensation of the presence of foreign body, the implants were well tolerated. Three patients lost the ocular mini insert spontaneously, whereas there was a function failure of the insert in four patients. Error grid analysis showed that the percentage of data pairs in the acceptable ranges (zone A and B) was very high (>96%). However, there was a shift from zone A to zone B during observation. This was due primarily to an increase in the lag time between capillary and interstitial measured glucose. CONCLUSION: he present study demonstrates good tolerability and measurement performance of the biosensor. The reasons for an increase in the lag time are still unknown; local reactions may be involved.
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Técnicas Biosensibles/instrumentación , Automonitorización de la Glucosa Sanguínea/instrumentación , Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Adulto , Conjuntiva/cirugía , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Seguridad de Equipos , Hemorragia/etiología , Humanos , Persona de Mediana Edad , Monitoreo Fisiológico/instrumentación , Complicaciones Posoperatorias/etiología , Prótesis e Implantes/efectos adversos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
BACKGROUND: Previous randomized controlled trials demonstrated a protective effect of renin angiotensin system blocking agents for the development of type-2 diabetes in patients with pre-diabetes. However, there are no real-world data available to illustrate the relevance for clinical practice. METHODS: Open, prospective, parallel group study comparing patients with an ACE inhibitor versus a diuretic based treatment. The principal aim was to document the first manifestation of type-2 diabetes in either group. RESULTS: A total of 2,011 patients were enrolled (mean age 69.1±10.3 years; 51.6% female). 1,507 patients were available for the per-protocol analysis (1,029 ramipril, 478 diuretic group). New-onset diabetes was less frequent in the ramipril than in the diuretic group over 4 years. Differences were statistically different at a median duration of 3 years (24.4% vs 29.5%; p<0.05). Both treatments were equally effective in reducing BP (14.7±18.0/8.5±8.2 mmHg and 12.7±18.1/7.0±8.3 mmHg) at the 4 year follow-up (p<0.001 vs. baseline; p=n.s. between groups). In 38.6% and 39.7% of patients BP was below 130/80 mmHg (median time-to-target 3 months). There was a significant reduction of cardiovascular morbidity and mortality in favour of ramipril (p=0.033). No significant differences were found for a change in HbA1c as well as for fasting blood glucose levels during follow-up. The rate of adverse events was higher in diuretic treated patients (SAE 15.4 vs. 12.4%; p<0.05; AE 26.6 vs. 25.6%; p=n.s). CONCLUSIONS: Ramipril treatment is preferable over diuretic based treatment regimens for the treatment of hypertension in pre-diabetic patients, because new-onset diabetes is delayed.
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Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/prevención & control , Diuréticos/uso terapéutico , Hipertensión/tratamiento farmacológico , Estado Prediabético/epidemiología , Ramipril/uso terapéutico , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Biomarcadores/sangre , Glucemia/metabolismo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Progresión de la Enfermedad , Diuréticos/efectos adversos , Femenino , Alemania/epidemiología , Hemoglobina Glucada/metabolismo , Humanos , Hipertensión/epidemiología , Hipertensión/fisiopatología , Incidencia , Masculino , Persona de Mediana Edad , Estado Prediabético/sangre , Estudios Prospectivos , Ramipril/efectos adversos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Recent clinical trials reported conflicting results on the reduction of new-onset diabetes using RAS blocking agents. Therefore the role of these agents in preventing diabetes is still not well defined. Ramipril is an ACE inhibitor (ACEi), that has been shown to reduce cardiovascular events in high risk patients and post-hoc analyses of the HOPE trial have provided evidence for its beneficial action in the prevention of diabetes. METHODS: The ADaPT investigation ("ACE inhibitor-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes") is a 4-year open, prospective, parallel group phase IV study. It compares an antihypertensive treatment regimen based on ramipril versus a treatment based on diuretics or betablockers. The primary evaluation criterion is the first manifestation of type 2 diabetes. The study is conducted in primary care to allow the broadest possible application of its results. The present article provides an outline of the rationale, the design and baseline characteristics of AdaPT and compares these to previous studies including ASCOT-BLPA, VALUE and DREAM. RESULTS: Until March 2006 a total of 2,015 patients in 150 general practices (general physicians and internists) throughout Germany were enrolled. The average age of patients enrolled was 67.1 +/- 10.3 years, with 47% being male and a BMI of 29.9 +/- 5.0 kg/m2. Dyslipidemia was present in 56.5%. 37.8% reported a family history of diabetes, 57.8% were previously diagnosed with hypertension (usually long standing). The HbA1c value at baseline was 5.6 %. Compared to the DREAM study patients were older, had more frequently hypertension and patients with cardiovascular disease were not excluded. CONCLUSION: Comparing the ADaPT design and baseline data to previous randomized controlled trial it can be acknowledged that AdaPT included patients with a high risk for diabetes development. Results are expected to be available in 2010. Data will be highly valuable for clinical practice due to the observational study design.
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Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Diabetes Mellitus Tipo 2/prevención & control , Diuréticos/uso terapéutico , Estado Prediabético/tratamiento farmacológico , Ramipril/uso terapéutico , Anciano , Interpretación Estadística de Datos , Progresión de la Enfermedad , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Estudios Prospectivos , Tamaño de la MuestraRESUMEN
BACKGROUND AND PURPOSE: Diabetic patients with nephropathy show a decline of hemoglobin even at a moderate degree of kidney dysfunction which may impair cardiovascular prognosis. As main reason a disturbed synthesis of erythropoietin (EPO) has been suggested, the pathogenesis, however, is unclear. The clinical significance of metabolic control for the hemoglobin and EPO levels was investigated. PATIENTS AND METHODS: The following parameters were determined in 185 type 1 diabetic patients: hemoglobin, HbA1c, calculated creatinine clearance, urinary albumin/creatinine ratio, lipids, high-sensitive C-reactive protein (hsCRP). Serum concentration of EPO was determined in 56 consecutive patients with renal dysfunction. RESULTS: Hemoglobin concentration decreased with declining renal function. Patients were stratified according to median HbA1c level (7.4%) in those with better (HbA1c < 7.4%) and worse metabolic control (HbA1c > 7.4%). In patients with kidney dysfunction, the group with better metabolic control showed higher hemoglobin concentrations than the group with worse metabolic control: 13.6 versus 12.6 g/dl at creatinine clearance < 60 ml/min (p = 0.02). Linear regression analysis revealed metabolic control aside from kidney function, gender, hsCRP and use of ACE inhibitiors as a significant influencing factor of hemoglobin concentration. In patients with renal dysfunction, EPO levels were higher in the group with better than worse metabolic control (13.0 vs. 9.8 U/l). CONCLUSION: The decline of hemoglobin in diabetic patients with renal dysfunction is mitigated in case of good metabolic control, possibly due to higher EPO concentrations. The results emphasize the clinical significance of a good metabolic control in diabetic patients with nephropathy.
Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Nefropatías Diabéticas/terapia , Eritropoyetina/sangre , Hemoglobina Glucada/análisis , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Índice de Masa Corporal , Colesterol/sangre , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Triglicéridos/sangreRESUMEN
PURPOSE: Early restenosis is one of the major complications after successful percutaneous transluminal angioplasty (PTA), in main, as well as peripheral, arteries. The effectiveness of hypofractionated external beam radiotherapy (EBRT) as a prophylaxis for restenosis was examined in a prospective, randomized, double-blind, clinical trial. METHODS AND MATERIALS: Forty-eight patients underwent sham RT and 47 were treated with daily RT in 3-Gy fractions, to a total dose of 21 Gy. The follow-up lasted for 12 months, and the examinations included pressure measurements and calculations of the ankle-brachial index or duplex sonography ("peak velocity ratio"). If restenosis was suspected, additional angiography was performed. RESULTS: No statistically significant difference was found between the treatment groups: sham RT 16 failures (33.3%) and EBRT group 21 failures (45.7%; p = 0.292). EBRT also showed no substantial effects on subgroups classified by the specific length of the lesion or in diabetic patients. CONCLUSION: External beam radiotherapy does not prevent restenosis. A reduction in the failure rate >8% using fractionated EBRT with doses aimed at keloid prevention can be ruled out with a probability of 97.5%. Endovascular brachytherapy remains the preferred therapeutic method for achieving restenosis prophylaxis through RT.
Asunto(s)
Angioplastia de Balón , Enfermedades Vasculares Periféricas/prevención & control , Anciano , Constricción Patológica/prevención & control , Constricción Patológica/radioterapia , Método Doble Ciego , Femenino , Arteria Femoral , Humanos , Arteria Ilíaca , Masculino , Enfermedades Vasculares Periféricas/radioterapia , Enfermedades Vasculares Periféricas/terapia , Arteria Poplítea , Estudios Prospectivos , Prevención SecundariaRESUMEN
OBJECTIVE: To evaluate the influence of renal impairment on the safety and efficacy of repaglinide in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: This multinational, open-label study comprised a 6-week run-in period, continuing prestudy antidiabetic medication, followed by a titration period (1-4 weeks) and a 3-month maintenance period. Patients with normal renal function (n = 151) and various degrees of renal impairment (n = 130) were treated with repaglinide (maximal dose of 4 mg, three times daily). Safety and efficacy assessments were performed at baseline (end of run-in) and at the end of study treatment. RESULTS: The type and severity of adverse events during repaglinide treatment were similar to the run-in period. The number of patients with adverse events was not significantly related to renal function during run-in or repaglinide treatment. Percentage of patients with hypoglycemic episodes increased significantly (P = 0.007) with increasing severity of renal impairment during run-in but not during repaglinide treatment (P = 0.074). Metabolic control (HbA(1c) and fasting blood glucose) with repaglinide was unchanged from that on previous antidiabetic medication. Final repaglinide dose tended to be lower for patients with severe and extreme renal impairment than for patients with less severe renal impairment or normal renal function (P = 0.032). CONCLUSIONS: Repaglinide has a good safety and efficacy profile in type 2 diabetic patients complicated by renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal impairment.